Sage Journals: Discover world-class research

Abstract

Damage to bones resulting from trauma and tumors poses a significant challenge to human health. Consequently, current research in bone damage healing centers on developing three-dimensional (3D) scaffolding materials that facilitate and enhance the regeneration of fractured bone tissues. In this context, the careful selection of materials and preparation processes is essential for creating demanding scaffolds for bone tissue engineering. This is done to optimize the regeneration of fractured bones. This study comprehensively analyses the latest scientific advancements and difficulties in developing scaffolds for bone tissue creation. Initially, we clarified the composition and process by which bone tissue repairs itself. The review summarizes the primary uses of materials, both inorganic and organic, in scaffolds for bone tissue engineering. In addition, we present a comprehensive study of the most recent advancements in the mainstream techniques used to prepare scaffolds for bone tissue engineering. We also examine the distinct advantages of each method in great detail. This article thoroughly examines potential paths and obstacles in bone tissue engineering scaffolds for clinical applications.

Graphical Abstract

Keywords

3D-implants biocompatibility clinical applications regenerative medicine

Introduction

Three-dimensional (3D) printing, or additive manufacturing, is a cutting-edge technique that enables the production of 3D items by building them layer by layer, using a digital design as a blueprint^1–4. The process commences with a digital file, such as a computer-aided design (CAD) model, serves as a blueprint for the desired object^5,6. The computerized model is segmented into thin, cross-sectional layers, then printed or deposited using various materials and techniques^7,8. Multiple 3D printing techniques are available, each with unique features and materials that can be used^9,10. Widely used methods include fused deposition modeling (FDM), stereolithography (SLA), selective laser sintering (SLS), and binder jetting. In addition, ceramics are utilized in 3D printing, which has significantly progressed in various industries, such as electronics and healthcare. Ceramic powders are employed in ceramic 3D printing^11,12.

Hybrid materials (HMs) denote one of the most emergent material classes at the edge of technological advancements¹³. Material properties achieved via a synergetic combination of more than one component on the molecular scale make HMs attractive for several applications¹⁴. There are several approaches to the classification of HM. They can be based on the source of origin, bonding, properties, and formation route, and highly favored materials in 3D printing¹⁵. Commonly utilized materials include PCL, PLA/HA, PCL/GelMA, Silk Fibroin/Bioactive Glass, Chitosan/β-TCP, and PLGA/Collagen. Every hybrid variety has unique attributes, such as its durability, flexibility, resistance to temperature changes, and ease of printing^16,17. 3D printing utilizes metal as a substitute material¹⁸.

Metals such as cobalt-chrome, titanium, stainless steel, and aluminum are usually cast-off in additive manufacturing^19,20. Durable metal components are produced through the layer-by-layer fusion of metal powders utilizing selective laser melting (SLM) or electron beam melting (EBM) techniques in metal 3D printing²¹. In addition, ceramics are used in 3D printing, which has advanced uses in industries including electronics and healthcare. Ceramic powders are used in ceramic 3D printing²².

The human skeletal system functions as a fundamental framework, offering structural support and safeguarding the organism^23,24. Nevertheless, various causes, such as the natural process of aging, physical injuries, or medical conditions, can contribute to the diminished strength or impairment of bones, ultimately resulting in substantial health complications^25,26. Lately, there has been an increasing fascination with advancing novel techniques for identifying, measuring, and identifying diseases through various means²⁷. To properly treat bone illnesses and injuries, it is necessary to utilize tissue engineering and regenerative medicine procedures²⁸. One practical approach in biomedical applications is the utilization of bone scaffolds. These scaffolds are like a 3D framework for tissue regeneration and promote the development of new tissues and bones²⁹. Because bone tissue is self-repairing and regenerating, minor flaws typically disappear independently. However, when bone abnormalities grow more significant than a critical size barrier (about >2 cm), the healing process is inadequate and frequently fails to mend^30–32. Every year, 4 million people worldwide need bone replacement surgery or grafts^33,34. As a result, treating bone abnormalities effectively is crucial from a clinical standpoint^35,36. In clinics, bone grafting is a mainstay. Depending on the circumstances, the defect site can heal successfully using different grafts^37,38.

Customized solutions for individual patients: 3D printing produces bone scaffolds tailored to each patient’s needs³⁹. This individualized strategy optimizes the efficacy of the treatment, enhancing bone rejuvenation consequences and minimizing the likelihood of problems⁴⁰. Biocompatibility: 3D-printed bone scaffolds can be fabricated using biocompatible materials, such as bioceramics or biodegradable polymers, which are highly compatible with the human body⁴¹. These compounds enhance cell attachment, proliferation, and differentiation, aiding the regeneration of new bone tissue⁴². This article concisely summarizes the recent advancements in the research and enhancement of 3D printing methods for producing scaffolds utilized in bone tissue engineering⁴³.

Critical Requirements for 3D Printed Scaffolds

3D printing has significantly transformed the field of tissue engineering and regenerative medicine, specifically in the field of bone scaffolds^44,45. Researchers can develop scaffolds that imitate the form and function of genuine bone by using biomaterials, advanced 3D printing technology, and detailed design procedures^46,47. Scaffolds provide customized mechanical characteristics, such as rigidity, durability, and adaptability, together with interconnected porous structures that improve the infiltration of cells and the exchange of nutrients^48,49. 3D-printed bone scaffolds are an excellent choice for patients requiring bone regeneration as long as they fulfill the criteria of biocompatibility, scaffold structure, sterilization, and regulatory compliance^19,50. These scaffolds offer individualized bone repair, tissue regeneration, and enhanced quality of life. To achieve this objective, the initial and most crucial stage is thoroughly comprehending the requirements^51,52. They are given in Table 1.

Table 1.

Biomedical Application and Properties of Hybrid Scaffolds for Clinical Application.

Scaffold type	Materials	3D printing technology	Pore Size (µm)	Mechanical properties	Biological properties	Growth factors	Degradation rate (months)	Applications	Ref
Scaffold 1	PLA/HA	Fused deposition modeling	300–500	Compressive Strength: 5 MPa	Supports osteoblast proliferation	BMP-2	6–12	Bone tissue engineering	⁵³
Scaffold 2	PCL/GelMA	Stereolithography (SLA)	100–300	Elastic Modulus: 50 MPa	Enhances vascularisation	VEGF, TGF*-β1	12–18	Cartilage regeneration	⁵⁴
Scaffold 3	PLGA/collagen	Selective laser sintering	200–400	Tensile Strength: 10 MPa	Promotes cell adhesion and growth	FGF*-2	4–6	Soft tissue engineering	⁵⁵
Scaffold 4	PEGDA/HAp	Digital Light Processing	250–350	Flexural Strength: 15 MPa	High biocompatibility	IGF*-1	3–5	Dental implants	⁵⁶
Scaffold 5	Silk fibroin/bioactive glass	Inkjet Printing	150–250	Shear Modulus: 20 MPa	Stimulates osteogenic differentiation	BMP*-7	8–10	Bone grafts	⁵⁷
Scaffold 6	Chitosan/β-TCP*	Extrusion Bioprinting	200–500	Compressive Modulus: 6 MPa	Antibacterial properties support chondrocyte growth	PDGF*, TGF-β3	3–6	Cartilage and bone regeneration	⁵⁸
Scaffold 7	Alginate/GelMA	Micro Extrusion	100–200	Young’s Modulus: 1–2 MPa	Supports angiogenesis, biocompatible	VEGF, bFGF*	1–3	Vascular tissue engineering	⁵⁹
Scaffold 8	PEEK*/carbon nanotubes	Melt Extrusion	400–600	Elastic Modulus: 5–10 MPa	Enhanced mechanical properties support osteogenesis	BMP-2, IGF-1	Less than 24	Load-bearing orthopedic implants
Scaffold 9	Hyaluronic acid/PLGA	Electrospinning	50–150	Compressive Strength: 3 MPa	Promotes wound healing, supports fibroblast activity	EGF, PDGF	2–4	Skin tissue engineering	⁶⁰
Scaffold 10	PVA*/hydroxyapatite	Direct Ink Writing	150–350	High tensile strength: 80 MPa	Osteoconductive, supports osteoblast proliferation	BMP-4	6–8	Bone defect repair	⁶¹

TGF-β1: Transforming growth factor beta 1*FGF: fibroblast growth factor*IGF: Insulin-like growth factor *PDGF: platelet-derived growth factor *bFGF: basic fibroblast growth factor *EGF: epidermal growth factor *β-TCP: beta-tricalcium phosphate *PEEK: polyether ether ketone *PVA: polyvinyl alcohol.

While there have been thorough examinations of scaffolds made from metal, ceramic, and polymers, more research is needed on hybrid scaffolds for advanced therapeutic purposes^62,63. It is imperative to thoroughly investigate how hybrid scaffolds might effectively address crucial therapeutic requirements^64,65. This encompasses a brief comprehension of their function in biomimetics, accurate bone regeneration, focused drug administration, tumor therapy, and infection treatment^66,67. Exploring the incorporation of biomimetic characteristics into these scaffolds remains an unexplored domain, and conducting research is crucial to enhance compositions for more efficient bone regeneration^68,69. Furthermore, there are unexplored possibilities in regulated drug administration, targeted treatments, and infection control^70,71.

The Mechanism for Repairing Bone Tissue

The bone tissue repair and healing process is intricate and consists of several phases^72,73. These stages primarily include inflammation and the formation of a blood clot, the recruitment and multiplication of stem cells, the development of blood vessels, the specialization of mesenchymal stem cells (MSCs), and the final phase of tissue remodeling^74,75. Fractures disrupt a specific area of the blood vessels and nearby tissue, creating a hematoma and the following inflammatory phase. Within 24 hours following the fracture, the soft matrix at the hematoma site attracts immune cells to facilitate an inflammatory response^76,77. After some time (week), the hematoma and inflammatory response are resolved, and the hematoma site is replaced by granulation tissue^78,79. Following the inflammatory and hematoma phase, many cells, including osteoblasts and endothelial cells, become active at the location of the defect. In addition to the proliferation of stem cells, angiogenesis occurs throughout the bone tissue healing process^80,81. Many blood vessels in bone are crucial for bone regeneration Fig. 1. The process of ultimate bone remodeling is a physiological phenomenon significantly influenced by the interaction between osteoblasts and osteoclasts^82,83. An essential objective is to integrate the attributes and principles of each step in bone tissue restoration with scaffolds, enhancing the performance of the scaffold materials through targeted alterations to attain superior and more effective outcomes in treating bone abnormalities⁸⁴.

Figure 1.

Schematic illustration of bioactive response of 3D-printed scaffolds during physiological immersion.

The Scaffold Structure Design Ensures Safety and Efficiency on Construction Sites

A 3D model of the scaffold can be created and transformed into a printable setup like Stereolithography (STL)^85,86. Customized scaffold shapes could be generated via CAD software based on specific patient structural anatomical data about the lesion^87,88. A 3D model is created by analyzing the anatomical data of the affected area, which is collected using computed tomography (CT) or magnetic resonance imaging (MRI)⁸⁹. Med CAD design and interfaces, inverse engineering surfaces, and STL-triangle shape model converting procedures are various approaches to creating CAD models from therapeutic pictures⁹⁰. Scaffolds and porous architecture are essential in tissue regeneration as they maintain tissue volume, fulfill temporary mechanical roles, and transport biofactors⁹¹. An effective scaffold will integrate mechanical functionality with the delivery of biofactors, facilitating a gradual transformation from scaffold to regenerated tissue as the previous scaffold breaks down⁹².

Consequently, the scaffold structure should imitate the inherent properties of genuine bone, including interconnecting pores^93,94. The scaffold’s porosity is crucial for cell intrusion, nutrition exchange, and tissue amalgamation. Researchers can use 3D printing to design and fabricate pores of varying sizes and forms^95–97. Fig. 2 explains the different properties required to construct the 3D scaffolds including their design, (shape, pore size, morphology) biofunctionality, (hemocompatibility, bioactivity, angiogenesis and osteointegration) manufacturing (electrospinning, SLA and 3D printing) strength (mechanical integrity, poor strength, stiffness, load bearing capacity and toughness) microstructures (degradation rate, chemical stability, processibility and crystallinity).

Figure 2.

Multifaceted evaluation parameters, including design, functionality, manufacturing, mechanical integrity, and microstructure, are required for the development of an ideal scaffold.

Tissue Engineering

Tissue engineering is a promising therapy option that uses engineering concepts to alleviate tissue damage^98,99. The field consists of three essential elements: scaffolds, cells, and growth factors. Bioreactors play a vital role in tissue engineering^3,100. The ideal scaffolds function as structural reinforcement for damaged tissue, transforming the growth factors produced by cancer cells into stimuli that promote tissue regeneration. Conventional approaches to treating tissue injury have faced substantial challenges throughout the years¹⁰¹.

Recent progress in bone tissue engineering has integrated growth factors and other biomolecules into scaffolds to direct cell behavior during the regeneration of organs and tissues^102,103. In the past 20 years, advances have been achieved in developing and applying biological scaffold materials^46,104. The three primary components of bone tissue engineering are bone progenitor cells, bone growth factors, and scaffolds^90,105. These elements work together to promote cell adhesion, maintain cell function, and imitate the natural process of bone tissue regeneration^106,107. The scaffold must serve as a transient template for cell regeneration of new bone tissue while also being capable of degradation to allow for replacement by the newly formed bone tissue^108,109. The scaffold’s primary function is to create an ideal microenvironment for cells, facilitating new tissue production and distribution of nutrients between the cells and their surroundings¹¹⁰.

Bone Scaffold Formation

Temporary constructs known as porous scaffolds facilitate the regeneration of bone tissue by providing an appropriate environment. They promote cell attachment, growth, specialization, and migration to the injury site^111,112. Scaffolds are essential to tissue engineering because they offer the best extracellular matrix (ECM) for progenitor cell proliferation and differentiation¹¹³. These cells can enter the scaffold and start the development, differentiation, multiplication, and migration processes because they react to biochemical and physical cues in their environment^114,115. When the environment is favorable, the cells secrete ECM and produce new tissues¹¹⁶. The best scaffolds have strong adhesion to bone-forming cells, biodegradability, robustness, and consistency in their mechanical properties¹¹⁷. The cells must be able to move toward the scaffold, stick to it, and multiply. Another essential feature is the scaffold’s connected porosity, which permits precise cell development and spreading inside the porous structure¹¹⁸.

This facilitates efficient angiogenesis in the surrounding tissue. The objective of constructing bone scaffolds is to produce an environment demonstrating biophysical, biomechanical, and biochemical features responsible for cell growth, specialization, and viability. Polymers, ceramics, and metals are the primary categories of biodegradable materials that have lately been examined in clinical and research settings^119,120. Therefore, a scaffold is a crucial element in tissue engineering, and to fulfill its essential function, it must possess the features mentioned above¹²¹.

Clinical Applications of 3D-printed Scaffolds

Wound and Infection Healing

A wound is a disruption or break in the skin caused by physical or thermal damage or a pathological cause¹²². The nature and severity of wounds vary depending on their underlying etiology, clinical manifestations, healing processes, or anatomical location¹²³. Regardless of their characteristics, wounds pose a significant healthcare challenge in the development of chronic diseases as they can raise healthcare expenses and complicate both internal and external health¹²⁴. Wound healing involves a range of well-coordinated molecular processes, including hemostasis, inflammation, proliferation, and remodeling¹²⁵.

Using 3D scaffolds with stem cell delivery has shown great potential in regenerative medicine. Wang et al. explained the examples of cell types include bone marrow mesenchymal stem cells, human umbilical cord perivascular cells (HUCPVC), and amniotic fluid-derived cells¹²⁶. Stem, endothelial progenitor, and circulating angiogenic cells (CACs) are frequently studied. Haki et al. utilize early endothelial progenitor cells (EPCs), also known as CACs, derived from peripheral blood mononuclear cell fraction and can be used locally to address nonhealing diabetic foot ulcers^127,128. Lv et al. does the augmentation in the formation of new blood vessels and a higher proportion of wound healing was noted when a scaffold made of collagen was used to transfer CACs to a diabetic rabbit ear wound (specifically, an ulcer produced by alloxan)¹²⁹. A 3D membrane scaffold, derived from a freeze-dried conditioned medium of bone marrow mesenchymal stem cells (FBMSC-CM), effectively expedited wound healing and improved the formation of new blood vessels (neovascularization) and the growth of epithelial tissue (epithelialization) by enhancing the presence of nourishing elements in the wound area^130,131. Fig. 3 explains the phenomena of wound healing for a long time and how hemostasis occurs due to 3D implant scaffolds, the formation of new cells, and epithelisation leading toward the remodeling of skin or wound repair.

Figure 3.

Mechanism of wound healing from hours to months adopted with permission¹²².

Tumor Therapy

3D scaffolds represent a promising solution in tumor therapy by providing a controlled and replicable microenvironment for studying cancer progression and testing treatments ¹¹¹. Many 3D scaffolds are used to treat tumors like novel bioceramic scaffolds. These scaffolds can be engineered to mimic the ECM of tumors, allowing for more accurate modeling of tumor growth, invasion, and metastasis ¹¹⁵. By incorporating bioactive molecules, such as drugs, growth factors, or genetic material, 3D scaffolds can deliver targeted therapies directly to the tumor site, potentially enhancing the efficacy and reducing the side effects of conventional treatments ¹²⁹. Moreover, Fig. 4 explains the mechanism of how local sites of proteins and membranes are being damaged by the heat-generated functional scaffolds, leading to apoptosis and cell death. As a result, scaffolds exhibiting superior photothermal or magnetothermal properties are highly effective as localized treatment agents. The ability to personalize these scaffolds based on patient-specific tumor characteristics facilitates the development of tailored therapeutic strategies, paving the way for more effective and individualized cancer treatments^125,129.

Figure 4.

Schematic illustration of a bifunctional scaffold with significant potential for clinical use in bone tumor therapy. The scaffold demonstrates pronounced capabilities for both regenerating bone tissue and treating tumors.

Cartilage and Spine Injury

Cartilage is a soft bone with a minimal capacity for regeneration. When a lesion, such as osteoarthritis, is created, more innovative explanations are needed. Lan et al.¹³² employed a scaffold using human nasal and chondrocytes using type 1 collagen. The scaffold was implanted in the mouse skin, and after 9 weeks, the printed cartilage regenerated its original shape and size. Cell viability decreased during the construction of the 3D structure. Similarly, after subcutaneous implantation, Beketov et al.¹³³ produced the scaffold using the bio-ink consisting of 4% collagen and chondrocytes. The cartilage tissue contains a high amount of COL2 and glycosaminoglycan (GAG).

A spine injury can be caused by accidents, swelling, dislocation, extrusion, and ischemia, leading to the damage of irreparable nerve cells. Neural stem cells (NSC) and their spatial distribution in the spinal cord is the route toward its successful repair again. Liu et al.¹³⁴ used different HMs to prepare the scaffold, such as bio-ink containing the mixed NSCs, hyaluronic acid derivatives, and chitosan. After implantation in the rats, it restored the locomotor abilities, called viability, and renewed axons. Similarly, another study explained how 3D-generated scaffolds with the help of gelatin combined with oligodendrocytes and NSCs improved motor skills and the production of new axons and neurons after implantation^28,135.

Heart Disease and Liver Failure

Decrease of cardiac fibrosis, cardiomyocyte hypertrophy, and increase of vascular formation using the 3D-constructed scaffold to treat the congenital heart disease of right ventricle failure in the rat model by using the bio-ink containing progenitor cells laden cardiac ECM gelatin and neonatal human c-kit¹³⁶. Similarly, to produce elongated cells that can contract, embedding the printed construct between 2 layers of rat omentum over a week using hydrogel with iPSCs differentiated into cardiomyocytes and patient-specific endothelial cells¹³⁷.

Human hepatocytes and methacrylate gelatin bio-ink were used to treat liver failure in mice. A 3D scaffold constructed stimulated liver cells’ vascularization and normal function¹³⁸. However, scaffolding in the mouse liver damage increased albumin expression and accelerated cell proliferation by using the 3% alginate hydrogel with induced hepatocyte cells¹³⁹. In addition, Table 2 explains the present challenges and their solution provided by 3D technology.

Table 2.

Detailed Table with Additional Clinical Challenges and Their 3D Printing Solutions.

Clinical challenges	Description	3D printing solution	References
Complex Bone Structures	Bones have intricate shapes and internal structures that are difficult to replicate accurately.	3D printing allows precise control over the shape and internal architecture, creating patient-specific, complex structures.	¹⁴⁰
Biocompatibility and Integration	Ensuring the material is biocompatible and integrates well with native bone tissue.	3D printing uses biocompatible materials and creates surface textures that promote better tissue integration.	⁷⁵
Mechanical Strength	Regenerated bone must have sufficient mechanical strength to withstand physiological loads.	3D printing customizes scaffold properties for optimal mechanical strength and porosity.	¹⁴¹
Vascularization	The formation of blood vessels within the scaffold is essential for supplying nutrients and removing waste.	3D-printing designs scaffolds with channels and pores that facilitate vascularization and can incorporate growth factors or cells.	⁹³
Customization and Personalization	Each bone defect is unique, requiring personalized treatment approaches.	3D printing produces patient-specific implants based on imaging data, ensuring a perfect fit and better functional outcomes.	^2,4
Cost and Accessibility	Traditional methods are often expensive and time-consuming, limiting accessibility.	3D printing can reduce custom implants’ cost and production time, making personalized treatments more accessible.	¹⁴²
Infection Risk	Implantation can introduce infections, complicating healing and regeneration.	3D printing can incorporate antimicrobial agents into the scaffold material, reducing infection risks.	¹⁴³
Healing Time	Long healing times can result in complications and prolonged recovery periods.	3D-printed scaffolds can be designed to release growth factors that accelerate bone regeneration and healing.	¹⁰
Osteoinductivity	The ability of a material to induce bone formation is critical for successful regeneration.	3D printing allows for the incorporation of osteoinductive agents into the scaffold, promoting new bone growth.	¹⁴⁴
Structural Stability	Ensuring the scaffold maintains its shape and functionality over time is crucial.	3D-printed scaffolds can be designed with optimal degradation rates, balancing structural stability with tissue regeneration.	⁹⁰
Supply Chain and Scalability	Manufacturing and delivering custom implants on a large scale can be challenging.	3D printing enables on-demand, localized production of implants, improving supply chain efficiency and scalability.	¹⁰⁴

Hybrid Scaffolds

Hybrid scaffolds are a promising field of study because they combine multiple materials to create improved features better suited for various tissue engineering applications. PCL/collagen scaffolds have been employed to fabricate artificial human skin^145,146. The resulting material gains muscular tensile strength by combining collagen with a small amount of PCL. This makes it helpful in creating scaffolds perfect for human skin tissue engineering^147,148. Recent investigations indicate that NPs are widely utilized in biomedical applications, including biosensing of metabolites, drug delivery, bioimaging, anti-biofilm, and antibacterial applications ^149,150. A study utilized PCL combined with titanium oxide, which has antibacterial properties and is coated with collagen to create a wound dressing material with antibacterial capabilities^103,151. A different research study utilized human endometrial stem cells (hEnSCs) by introducing them into a PCL/collagen scaffold to create an innovative structure for skin engineering¹⁵². Due to the endometrium’s remarkable regenerative ability, this nanofiber was suggested to stimulate angiogenesis without needing growth hormones. This indicates its potential for repairing skin tissue during wound healing¹⁵³. A composite of poly L-lactide (PLLA) and chitosan was created to preserve the essential properties of both materials. PLLA possesses high mechanical strength but is not conducive to cell growth¹⁵⁴.

On the contrary, chitosan demonstrates favorable tissue regeneration capabilities, but it lacks sufficient strength^58,105. Consequently, collagen was utilized to construct scaffolds with funnel-shaped structures with pores, enabling the cells to proliferate and establish connections beneath the surface ⁷⁷. Subsequently, the collagen funnels were positioned onto a PLLA mesh to create hybrid scaffolds. Animal experiments have demonstrated that applying these hybrid scaffolds to seed fibroblast cells can improve the repair of incisional lesions^17,52,126. Combining chitosan and silk nanofibrils has been utilized to create nanocomposite scaffolds that demonstrate excellent resistance to high temperatures and impressive mechanical durability¹²⁶. The nanocomposites share a comparable composition with the ECM, so they can produce a more sophisticated biomaterial for skin engineering¹⁵⁵. An article has described a bilayer nanocomposite scaffold made from silk fibroin, gelatin, and oxidized alginate. This scaffold has a structure comparable to the ECM and has the potential to be used in regenerative medicine and skin engineering¹⁵⁶. The efficacy of hybrid collagen scaffolds containing ZnO-curcumin nanocomposites was assessed to promote accelerated wound healing and minimize scarring¹⁵⁷. An 80% cell viability was recorded, indicating a favorable cell growth and attachment level. Experiments conducted on live albino rats showed an increase in the expression of TGF-β3 and a notable recovery of burnt wounds without scarring¹⁵⁸. A separate research project involved the creation of a nanocomposite scaffold using chitosan and PVA. This scaffold was infused with photogenic iron oxide nanoparticles (FeO NPs) to investigate their effects on diabetic wounds associated with anemia¹⁵⁹. The FeO NPs were synthesized using a leaf extract obtained from Pinus densiflora. The FeO NPs exhibited favorable anti-diabetic and antioxidant effects in biological experiments and antibacterial solid capabilities¹⁶⁰. The in vitro wound healing experiment demonstrated enhanced cellular proliferation by HEK 293 cells. These data indicate that this composite scaffold could be used for treating diabetic wounds, pending a thorough in vivo assessment^161,162. Table 3 summarizes various hybrid polymers utilized as scaffolds for applications in wound healing and skin tissue engineering¹⁶³.

Table 3.

shows the Advantages and Disadvantages of Various Hybrid Scaffold Materials Used in Biomedical Applications.

Material	Advantages	Disadvantages	Ref
PLA (polylactic acid)/HA (Hydroxyapatite)	–Biocompatible and biodegradable–Good mechanical properties–Promotes bone regeneration and integration	–Slow degradation rate,–Potential for acidic degradation products–Limited cell adhesion without surface modification	⁵³
PCL (polycaprolactone)/GelMA (gelatin methacrylate)	–Biocompatible and biodegradable–Flexible and elastic–Supports cell adhesion and proliferation–Tunable degradation rate	–Lower mechanical strength compared to some other materials–Possible immune response to gelatin components	⁹⁷
PLGA (poly[ acid])/collagen	–Excellent biocompatibility–Supports cell adhesion and growth–Tunable degradation rate–Versatile mechanical properties	–Potential for acidic degradation products–Rapid degradation rate can sometimes be too fast	⁷⁷
PEGDA (polyethylene glycol diacrylate)/HAp (hydroxyapatite)	–High biocompatibility–Tunable mechanical properties–Non–toxic degradation products–Supports osteogenic differentiation	–Limited mechanical strength for load–bearing applications–Requires functionalisation for enhanced cell interaction	¹⁶³
Silk fibroin/bioactive glass	–Excellent biocompatibility–Supports osteogenesis–Good mechanical properties–Bioactive properties	–Potential brittleness–Limited degradation rate control	¹⁶⁴
Chitosan/β-TCP (beta-tricalcium phosphate)	–Biocompatible and biodegradable–Antibacterial properties–Supports bone and cartilage regeneration	–Variable degradation rate–Mechanical properties can be lower than synthetic polymers	^77,105,58
Alginate/GelMA (gelatin methacrylate)	–Biocompatible and biodegradable–Supports cell proliferation–Easy to process and print–Promotes angiogenesis	Poor mechanical properties alone–Rapid degradation in physiological conditions	¹³⁴
PEEK (polyether ether ketone)/carbon nanotubes	Excellent mechanical properties–Biocompatible–Supports osteogenesis–High wear resistance	–Non–biodegradable–Potential toxicity of carbon nanotubes–Expensive and difficult to process	¹⁶⁵
Hyaluronic acid/PLGA (poly[ acid])	Excellent biocompatibilitySupports wound healingTunable degradation ratePromotes fibroblast activity	Potential for acidic degradation products–Requires stabilization for mechanical integrity	^60,166
PVA (polyvinyl alcohol)/hydroxyapatite	Biocompatible–Supports osteoblast proliferation–Good mechanical properties–Hydrophilic nature	–Non–biodegradable–Potential for rapid swelling and loss of mechanical properties in aqueous environments	¹⁶⁷

Future Perspectives

The application of 3D printing in bone tissue engineering is now undergoing extensive research and exploration. The primary benefit of this technology is its capacity to regulate the arrangement of fibers, leading to scaffolds that exhibit superior performance due to their optimized structure and function at many scales¹⁶⁸. Despite the advancements in 3D printing technology, certain constraints still impede the application of tissue engineering scaffolds in practical medical settings. For instance, the selection of printing materials is restricted¹⁶⁹. It is essential to consider the physiochemical qualities of the materials, such as rheology (flow behavior), wetting performance, and melting point¹⁷⁰.

In addition, their biological properties should also be considered, including biodegradability, biocompatibility, and cell interaction. Internal faults may arise during printing, leading to subpar mechanical quality in the printed product¹⁷¹. To utilize 3D printing technology effectively, it is crucial to thoroughly examine ink materials regarding material selection, design of 3D structures, and function novelty. Furthermore, the printing procedure is essential to optimize the associated parameters for high-quality outcomes^172,173. Although several fabrication material concerns have not yet been resolved, there is still ample opportunity to investigate beneficial approaches for bone tissue engineering. The current research on repairing infected bones needs a thorough grasp of the repair mechanism in a complicated model of infected bone defects^174,175. The currently described bone analogs possess only one specific function, and creating bone analogs capable of performing multiple tasks in an integrated manner remains a significant challenge¹⁷⁶. Vascularization is essential for developing organs in massive bone tissues, as they require a well-developed network of blood vessels to provide nutrients and oxygen. Regrettably, the construction of vascular networks remains a significant obstacle due to the low vascularization of bone tissue¹⁷⁷.

To efficiently address these glitches, it is vital to understand the inherent structural properties of bone tissue and the natural mechanisms involved in bone tissue healing and regeneration, including the impacts and interplay of many factors in infected bone defects¹⁷⁸. The design of bone tissue engineering scaffolds should aim to replicate the bionic structure of natural bone tissue. These scaffolds can be enhanced by incorporating inflammatory cytokines, ECM, and ligands. This integration allows for imitating the initial phases of bone regeneration and tissue repair^179–181.

Conclusion

Infected bone injuries and defects are still a core problem for orthopedic surgeons and practitioners. Engineering technologies and biological integration are critical elements in developing bone tissues. This review concisely discusses strategies for addressing bone defects through sustainable hybrid 3D-printed scaffold materials. A fundamental requirement for bone defects is the promotion of tissue regeneration and the stopping of bone infection. Many factors are responsible for this infection therapy, which include antibacterial coatings, bioactive metal ions, anti-infective drugs, and 3D-printed scaffolds that collectively fight against bone issues and treat osteomyelitis by producing the ideal microenvironment for rapid bone growth. Moreover, essential factors like photothermal, electric, and magnetic stimuli can be enhanced to promote bone regeneration during the loading of the 3D porous scaffolds. In tissue engineering, 3D-printed scaffold technology is currently the most reasonable solution for designing scaffolds according to infected patients’ complex shape injuries.

Footnotes

Authors Contribution

A.R.K. and N.S.G. wrote the manuscript and collected all the data. F M. O.T, F. T, and R. M.Z they also interpreted the manuscript’s results. H-J. Z. and Z. J. developed the theory and reviewed the manuscript.

Ethical Approval

This study was approved by our institutional review board.

Statement of Human and Animal Rights

This article does not contain any studies with human or animal subjects.

Statement of Informed Consent

There are no human subjects in this article and informed consent is not applicable.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research is supported by the Researchers Supporting Project Number (RSP2024R440), King Saud University, Riyadh, Saudi Arabia.

ORCID iD

Ahsan Riaz Khan

References

Poltue

Karuna

Khrueaduangkham

Seehanam

Promoppatum

. Design exploration of 3D-printed triply periodic minimal surface scaffolds for bone implants. Int J Mech Sci. 2021;211:106762. doi:10.1016/j.ijmecsci.2021.106762.

Mirkhalaf

Men

Wang

Zreiqat

. Personalized 3D printed bone scaffolds: a review. Acta Biomater. 2023;156:110–24.

Kennedy

Roy Choudhury

Parthasarathy

. 3D printing soft tissue scaffolds using Poly(caprolactone). Bioprinting. 2023;30:1–11

Wang

Huang

Zhou

Chen

Tian

Liao

Wei

. 3D printing of bone tissue engineering scaffolds. Bioact Mater. 2020;5:82–91.

Zhang

Zhou

Zhi

Liu

Fang

Zhang

. 3D printing method for bone tissue engineering scaffold. Med Nov Technol Devices. Epub 2023 Mar 17.

Liu

Nie

Wang

Zheng

Zhang

Peng

. 3D printed PCL/SrHA scaffold for enhanced bone regeneration. Chem Eng J 2019;362:269–79.

Zou

Pan

Tarafder

Geng

Chen

Lee

. Icariin-releasing 3D printed scaffold for bone regeneration. Compos B Eng. 2022;232: 109625.

Lima

Correlo

Reis

. Micro/nano replication and 3D assembling techniques for scaffold fabrication. Mater Sci Eng C Mater Biol Appl. 2014;42:615–21.

Chen

Shi

Zhang

. 3D printed hydroxyapatite composite scaffolds with enhanced mechanical properties. Ceram Int. 2019;45:10991–96.

10.

Yayehrad

Siraj

Matsabisa

Birhanu

. 3D printed drug loaded nanomaterials for wound healing applications. Regen Ther. 2023;24:361–76.

11.

Kanwar

Vijayavenkataraman

. Design of 3D printed scaffolds for bone tissue engineering: a review. Bioprinting. 2021;24:e00167. doi:10.1016/j.bprint.2021.e00167.

12.

Kondiah

Choonara

Kondiah

Marimuthu

du Toit

Kumar

Pillay

. Recent progress in 3D-printed polymeric scaffolds for bone tissue engineering. In: du Toit

Kumar

Pillay

Choonara

, editors. Advanced 3D-printed Systems and Nanosystems for Drug Delivery and Tissue Engineering. Elsevier; 2020, p. 59–81.

13.

Zhao

Cui

Wang

Chen

Wang

Zhang

Wang

. Regulation effects of biomimetic hybrid scaffolds on vascular endothelium remodeling. ACS Appl Mater Interfaces. 2018;10:23583–94.

14.

Moreno

Mohedano

Arrabal

Rodríguez-Hernández

Matykina

. Development of hybrid hierarchical coatings on Mg3Zn0.4Ca alloy for orthopaedic implants. J Mater Res Technol. 2023;24:5823–38.

15.

Ramkumar

Rijwani

. Additive manufacturing of metals and ceramics using hybrid fused filament fabrication. J Braz Soc Mech Sci Eng. 2022;44:455.

16.

González-Ulloa

Jiménez-Rosado

Benhnia

Romero

Ruiz-Mateos

Ostos

Perez-Puyana

. Hybrid polymeric Hydrogel-based biomaterials with potential applications in regenerative medicine. J Mol Liq;. 2023;384.

17.

Chang

Peng

Teramoto

Nishio

Zhang

. Fabrication and properties of chitin/hydroxyapatite hybrid hydrogels as scaffold nano-materials. Carbohydr Polym. 2013;91:7–13.

18.

Sooriyaarachchi

Feng

Islam

Tan

. Hybrid fabrication of biomimetic meniscus scaffold by 3D printing and parallel electrospinning. Procedia Manuf. 2019;34:528–34.

19.

Rahmani

Kamboj

Brojan

Antonov

Prashanth

. Hybrid metal-ceramic biomaterials fabricated through powder bed fusion and powder metallurgy for improved impact resistance of craniofacial implants. Materialia. 2022;24:101465. doi:10.1016/j.mtla.2022.101465.

20.

Liu

Lin

Tang

Liu

Jiang

Lian

. Design of metal-polymer structure for dental implants with stiffness adaptable to alveolar bone. Composites Communications. 2021;24:100660. doi:10.1016/j.coco.2021.100660.

21.

Elsayed

Jayakumar

Abdellah

Mansoure

Zheng

Elewa

Chang

Ting

Lin

Wang

. Visible-light-driven hydrogen evolution using nitrogen-doped carbon quantum dot-implanted polymer dots as metal-free photocatalysts. Appl Catal B, 2021; 283:119659.

22.

Kim

Ahn

Ryu

Kim

Shim

Kim

Yun

. In vitro study of three-dimensional printed metal-polymer hybrid scaffold incorporated dual antibiotics for treatment of periprosthetic joint infection. Mater Lett. 2018;212:263–66.

23.

Silva

Felismina

Mateus

Parreira

Malça

. Application of a hybrid additive manufacturing methodology to produce a metal/polymer customized dental implant. Procedia Manuf. 2017;12:150–55.

24.

Bretosh

Hallais

Chevalier-Cesar

Zucchi

Bodelot

. Gold metallization of hybrid organic-inorganic polymer microstructures 3D printed by two-photon polymerization. Surfaces and Interfaces. 2024;39:102895.

25.

Nieman

Wentz

. The compelling link between physical activity and the body’s defense system. J Sport Health Sci. 2019;8(3):201–17.

26.

Nieman

. Clinical implications of exercise immunology. J Sport Health Sci. 2012;1:12–17.

27.

Moura

de Araújo

de Vasconcelos Gurgel

Dal Piva

Ozcan

e Souza

. Clinical performance of monolithic polymer-infiltrated ceramic and lithium disilicate posterior crowns: a controlled, randomized, and double-blind clinical trial. J Prosthet Dent. Epub 2023 Sep 8.

28.

Kara

Distler

Polley

Schneidereit

Seitz

Friedrich

Tihminlioglu

Boccaccini

. 3D printed gelatin/decellularized bone composite scaffolds for bone tissue engineering: fabrication, characterization and cytocompatibility study. Mater Today Bio. 2022;15:100309. doi:10.1016/j.mtbio.2022.100309.

29.

Raja

Han

Cho

Choi

Jin

Park

Lee

Yun

. Effect of porosity and phase composition in 3D printed calcium phosphate scaffolds on bone tissue regeneration in vivo. Mater Des. 2022;219:110819.

30.

Kanwar

Al-Ketan

Vijayavenkataraman

. A novel method to design biomimetic, 3D printable stochastic scaffolds with controlled porosity for bone tissue engineering. Mater Des. 2022;220:110857.

31.

Rastogi

Kandasubramanian

. Breakthrough in the printing tactics for stimuli-responsive materials: 4D printing. Chem Eng J. 2019;366:264–304.

32.

Patdiya

Kandasubramanian

. Progress in 4D printing of stimuli responsive materials. Polym Plast Technol Mater. 2021;60:1845–83.

33.

Wang

Zheng

Shi

Ren

Wang

. Construct scaffold-like delivery system with poly (lactic-co-glycolic) microspheres on micro-arc oxidation titanium. Appl Surf Sci. 2013;266:81–88.

34.

Browe

Díaz-Payno

Freeman

Schipani

Burdis

Ahern

Nulty

Guler

Randall

Buckley

Brama

. Bilayered extracellular matrix derived scaffolds with anisotropic pore architecture guide tissue organization during osteochondral defect repair. Acta Biomater. 2022;143:266–81.

35.

Singh

Batra

Kumar

Mahapatro

. Investigating TiO2–HA–PCL hybrid coating as an efficient corrosion resistant barrier of ZM21 Mg alloy. J Magnes Alloy. 2021;9:627–46.

36.

Singh

Batra

Kumar

Siddiquee

. Evaluating the Electrochemical and in vitro degradation of an HA-Titania Nano-channeled coating for effective corrosion resistance of biodegradable Mg alloy. Coatings. 2022;13:30.

37.

Xie

Cai

Chen

Wang

Hou

Steinberg

Rolauffs

El-Newehy

El-Hamshary

Jiang

, et al. Multiphasic bone-ligament-bone integrated scaffold enhances ligamentization and graft-bone integration after anterior cruciate ligament reconstruction. Bioact Mater. 2024;31:178–91.

38.

Wang

Shen

Hou

Wang

. 3D printing of reduced glutathione grafted gelatine methacrylate hydrogel scaffold promotes diabetic bone regeneration by activating PI3K/Akt signaling pathway. Int J Biol Macromol. 2022;222:1175–91.

39.

Shi

Liu

Zhang

Yin

Wang

. Effects of Ag, Cu or Ca addition on microstructure and comprehensive properties of biodegradable Zn-0.8Mn alloy. Mater Sci Eng C. 2019;99:969–78.

40.

Khan

Alnoud

MAH

Ali

Ahmad

Ul Hassan

Shaikh

Hussain

Khan

, et al. Beyond the beat: a pioneering investigation into exercise modalities for alleviating diabetic cardiomyopathy and enhancing cardiac health. Curr Probl Cardiol. 2024;49(2):102222. doi:10.1016/j.cpcardiol.2023.102222.

41.

Mahmood

Akram

Shenggui

Chen

. Revolutionizing manufacturing: a review of 4D printing materials, stimuli, and cutting-edge applications. Compos B Eng. 2023; 266:110952. doi:10.1016/j.compositesb.2023.110952.

42.

Kovaleva

Pariy

Chernozem

Zadorozhnyy

Permyakova

Kolesnikov

Surmeneva

Surmenev

Senatov

. Shape memory effect in hybrid polylactide-based polymer scaffolds functionalized with reduced graphene oxide for tissue engineering. Eur Polym J. 2022;181:111694.

43.

Ameen

Takhakh

Abdal-hay

. An overview of the latest research on the impact of 3D printing parameters on shape memory polymers. European Polymer Journal. 2023;194:112145.

44.

Calori

Braga

de Jesus

Tedesco

. Polymer scaffolds as drug delivery systems. Eur Polym J. 2020;129:109621.

45.

Tut

Cesur

Ilhan

Sahin

Yildirim

Gunduz

. Gentamicin-loaded polyvinyl alcohol/whey protein isolate/hydroxyapatite 3D composite scaffolds with drug delivery capability for bone tissue engineering applications. Eur Polym J. 2022;179:111580.

46.

Jang

Min

Kim

Shin

Lee

. Review: scaffold characteristics, fabrication methods, and biomaterials for the bone tissue engineering. Int J Precis Eng Manuf-Smart Tech. 2023;24:511–29.

47.

Di Giacomo

Cury

da Silva

Ajzen

. Surgical guides for flapless dental implant placement and immediate definitive prosthesis installation by using selective laser melting and sintering for 3D metal and polymer printing: a clinical report. J Prosthet Dent. 2022;131:177–79. doi:10.1016/j.prosdent.2022.05.034.

48.

Zhang

Liu

Zhou

Wang

Mickymaray

Alothaim

Kannaiyan

. In vitro investigation of cartilage regeneration properties of polymeric ceramic hybrid composite. J Saudi Chem Soc. 2022;26:101470.

49.

Aguero

Alpdagtas

Ilhan

Zaldivar-Silva

Gunduz

. Functional role of crosslinking in alginate scaffold for drug delivery and tissue engineering: a review. Eur Polym J. 2021;160:110807.

50.

Rohr

Brunner

Märtin

Fischer

. Influence of cement type and ceramic primer on retention of polymer-infiltrated ceramic crowns to a one-piece zirconia implant. J Prosthet Dent. 2018;119(1):138–45.

51.

Kiran

Kizhakeyil

Ramalingam

Verma

Lakshminarayanan

Kumar

Doble

Ramakrishna

. Drug loaded electrospun polymer/ceramic composite nanofibrous coatings on titanium for implant related infections. Ceram Int. 2019;45:18710–20.

52.

Sadeghianmaryan

Naghieh

Yazdanpanah

Sardroud

Sharma

Wilson

Chen

. Fabrication of chitosan/alginate/hydroxyapatite hybrid scaffolds using 3D printing and impregnating techniques for potential cartilage regeneration. Int J Biol Macromol. 2022;204:62–75.

53.

Zhang

Wang

Song

Pei

Sun

Zhou

Wang

Fan

Zhang

. 3D printed bone tissue regenerative PLA/HA scaffolds with comprehensive performance optimizations. Mater Des. 2021;201:109490.

54.

Dong

Zhang

Zhou

Shao

Wang

Chu

Xue

Yao

Bai

. 3D-printed Mg-incorporated PCL-based scaffolds: a promising approach for bone healing. Mater Sci Eng C. 2021;129:112372.

55.

Moncal

Aydin

RST

Abu-Laban

Heo

Rizk

Tucker

Lewis

Hayes

Ozbolat

. Collagen-infilled 3D printed scaffolds loaded with miR-148b-transfected bone marrow stem cells improve calvarial bone regeneration in rats. Mater Sci Eng C Mater Biol Appl. 2019;105:110128.

56.

Han

Lian

Zhang

Jia

Sun

Qiao

Sun

Dai

. Study on bioactive PEGDA/ECM hybrid bi-layered hydrogel scaffolds fabricated by electro-writing for cartilage regeneration. Appl Mater Today. 2022;28:101547.

57.

Logeshwaran

Srinivas

Venkatesh

Nayak

. Silk fibroin infilled 3D printed polymer-ceramic scaffold to enhance cell adhesion and cell viability. Mater Lett. 2023;347:134607.

58.

Jirofti

Hashemi

Moradi

Kalalinia

. Fabrication and characterization of 3D printing biocompatible crocin-loaded chitosan/collagen/hydroxyapatite-based scaffolds for bone tissue engineering applications. Int J Biol Macromol. 2023;252:126279.

59.

Koch

Thaden

Conrad

Tröndle

Finkenzeller

Zengerle

Kartmann

Zimmermann

Koltay

. Mechanical properties of polycaprolactone (PCL) scaffolds for hybrid 3D-bioprinting with alginate-gelatin hydrogel. J Mech Behav Biomed Mater. 2022;130:105219.

60.

Gouda

Almutairi

Abd El-Lateef

. Hyaluronic acid/cellulose acetate polymeric mixture containing binary metal oxide nano-hybrid as low biodegradable wound dressing. J Mater Res Technol. 2023;26:7925–35.

61.

Supriya Bhatt

Thakur

Nune

. Preparation and characterization of PVA/Chitosan cross-linked 3D scaffolds for liver tissue engineering. Mater Today Proc. Epub 2023 Mar 1. doi:10.1016/j.matpr.2023.02.251.

62.

Saneei Mousavi

Karami

Ghasemnejad

Kolahdouz

Manteghi

Ataei

. Design of a remote-control drug delivery implantable chip for cancer local on demand therapy using ionic polymer metal composite actuator. J Mech Behav Biomed Mater. 2018;86:250–56.

63.

Moaref

Shahini

Mohammadloo

Ramezanzadeh

Yazdani

. Application of sustainable polymers for reinforcing bio-corrosion protection of magnesium implants: a review. Sustain Chem Pharm. 2022;29:100780.

64.

Mohamadi

Hivechi

Bahrami

Nezari

Milan

Amoupour

. Fabrication and investigating in vivo wound healing property of coconut oil loaded nanofiber/hydrogel hybrid scaffold. Biomater Adv. 2022;142:213139.

65.

Krishna

Sankar

. Machine learning-assisted extrusion-based 3D bioprinting for tissue regeneration applications. Annals of 3D Printed Medicine, 2023;12:100132. doi:10.1016/j.stlm.2023.100132.

66.

Yang

Wen

Lee

Lui

. Cell response on the biomimetic scaffold of silicon nano- and micro-topography. J Mater Chem B. 2016;4:1891–97.

67.

Meier

Jang

. Surface design strategies of polymeric biomedical implants for antibacterial properties. Curr Opin Biomed Eng. 2023;26:100448.

68.

Ribas

Schatkoski

do Amaral Montanheiro

de Menezes

Stegemann

Leite

Thim

. Current advances in bone tissue engineering concerning ceramic and bioglass scaffolds: a review. Ceram Int. 2019;45:21051–61.

69.

Reivan Ortiz

Cespedes Panduro

Saba

Cotrina Aliaga

Mohany

Al Rejaie

Arias Gonzales

Ramiz Cornell

Kadham

Akhavan Sigari

. Adsorption of thiotepa anticancer by the assistance of aluminum nitride nanocage scaffolds: a computational perspective on drug delivery applications. Colloids Surf A Physicochem Eng Asp. 2023; 666:131276. doi:10.1016/j.colsurfa.2023.131276.

70.

Mehta

Saini

Singh

Buddhi

. Advancements in polymer composites as a pertinent biomaterial for hard tissue applications—a review. Mater Today Proc. 2022;69:344–48.

71.

Al-Shalawi

Hanim

Ariffin

Kim

Brabazon

Calin

Al-Osaimi

. Biodegradable synthetic polymer in orthopaedic application: a review. Mater Today Proc. 2023;74:540–46.

72.

Wang

Xiong

Pang

Sun

. 3D-printed scaffold with halloysite nanotubes laden as a sequential drug delivery system regulates vascularized bone tissue healing. Mater Today Adv. 2022;15:100259.

73.

Torres

Gaspar

Serra

Diogo

Fradique

Silva

Correia

. Bioactive polymeric-ceramic hybrid 3D scaffold for application in bone tissue regeneration. Mater Sci Eng C Mater Biol Appl. 2013;33(7):4460–69.

74.

Araújo

Viveiros

Philippart

Miola

Doumett

Baldi

Perez

Boccaccini

Aguiar-Ricardo

Verné

. Bioactivity, mechanical properties and drug delivery ability of bioactive glass-ceramic scaffolds coated with a natural-derived polymer. Mater Sci Eng C. 2017;77:342–51.

75.

Hasanzadeh

Mihankhah

Azdast

Rasouli

Shamkhali

Park

. Biocompatible tissue-engineered scaffold polymers for 3D printing and its application for 4D printing. Chem Eng J. 2023;476:146616.

76.

Tilton

Camilleri

Astudillo Potes

Gaihre

Liu

Lucien

Elder

. Visible light-induced 3D bioprinted injectable scaffold for minimally invasive tissue regeneration. Biomater Adv. 2023;153:213539.

77.

Baysan

Gunes

Turemis

Yilmaz

Husemoglu

Ozenler

Perpelek

Albayrak

Havitcioglu

Cecen

. Using loofah reinforced chitosan-collagen hydrogel based scaffolds in-vitro and in-vivo; healing in cartilage tissue defects. Materialia. 2023;31:101881. doi:10.1016/j.mtla.2023.101881.

78.

Ross

Kilian

Lode

Ren

Allenby

Gelinsky

Woodruff

. Using melt-electrowritten microfibres for tailoring scaffold mechanics of 3D bioprinted chondrocyte-laden constructs. Bioprinting. 2021;23:00158.

79.

Liu

Wang

Gong

Zhu

Shen

Zhu

Ren

Chen

Bian

. Ti6Al4V biomimetic scaffolds for bone tissue engineering: Fabrication, biomechanics and osseointegration. Mater Des. 2023;234:112330.

80.

Liu

Wang

Wei

Zhang

Bao

. Topology optimization for reducing stress shielding in cancellous bone scaffold. Comput Struct. 2023;288:107132.

81.

Bogala

. Three-dimensional (3D) printing of hydroxyapatite-based scaffolds: a review. Bioprinting. 2022;28:e00244.

82.

Anderson

Dubey

Bogie

Cao

Lerchbacker

Mendonça

Kauffmann

Bottino

Kaigler

. Three-dimensional printing of clinical scale and personalized calcium phosphate scaffolds for alveolar bone reconstruction. Dent Mater. 2022;38(3):529–39.

83.

Lin

Lee

Fang

Kuo

Shie

. The effects of a 3D-printed magnesium-/strontium-doped calcium silicate scaffold on regulation of bone regeneration via dual-stimulation of the AKT and WNT signaling pathways. Biomater Adv. 2022;133:112660.

84.

Yunsheng

Hui

Jie

Tingting

Naiqi

Jiaxing

Wei

Yufei

Qiang

Shufang

. Sustained release silicon from 3D bioprinting scaffold using silk/gelatin inks to promote osteogenesis. Int J Biol Macromol. 2023;234:123659.

85.

Sestito

Harris

TAL

Wang

. Structural descriptor and surrogate modeling for design of biodegradable scaffolds. J Mech Behav Biomed Mater. 2024;152:106415.

86.

Moheb Afzali

Kheradmand

Naghib

. Bioreactor design-assisted bioprinting of stimuli-responsive materials for tissue engineering and drug delivery applications. Bioprinting. 2023;37:e00298. doi:10.1016/j.bprint.2023.e00325.

87.

Cho

Ghim

Hong

Kim

Cho

. Strategy to improve endogenous bone regeneration of 3D-printed PCL/nano-HA composite scaffold: Collagen designs with BMP-2 and FGF-2. Mater Des. 2023;229:111913.

88.

Rahatuzzaman

Mahmud

Rahman

Hoque

. Design, fabrication, and characterization of 3D-printed ABS and PLA scaffolds potentially for tissue engineering. Results Eng. 2024;21:101685.

89.

Chen

Liu

Wang

Zhang

Chen

Han

Wang

. Design and properties of biomimetic irregular scaffolds for bone tissue engineering. Comput Biol Med. 2021;130:104241.

90.

Vaiani

Uva

Boccaccio

. Structural and topological design of conformal bilayered scaffolds for bone tissue engineering. Thin-Walled Struct. 2023;192:111209.

91.

Shi

Gao

Zhang

Liu

Zhou

Yin

Wang

. Design biodegradable Zn alloys: second phases and their significant influences on alloy properties. Bioact Mater. 2020;5(2):210–18.

92.

Cwieka

Wysocki

Skibinski

Chmielewska

Swieszkowski

. Numerical design of open-porous titanium scaffolds for Powder Bed Fusion using Laser Beam (PBF-LB). J Mech Behav Biomed Mater. 2024;151:106359.

93.

Luo

Zhang

Lin

. 3D printed hydrogel scaffolds with macro pores and interconnected microchannel networks for tissue engineering vascularization. Chem Eng J. 2022;430:132926.

94.

Zhang

Chen

Sun

Yang

Chen

Xiong

Hou

Bai

. Design of a biomimetic graded TPMS scaffold with quantitatively adjustable pore size. Mater Des. 2022;218:110665.

95.

Kennedy

Amudhan

Robert

Vasanthanathan

Pandian

. Experimental and finite element analysis on the effect of pores on bio-printed polycaprolactone bone scaffolds. Bioprinting. 2023;34:e00301.

96.

Liu

Feng

. Effects of pore size on the mechanical and biological properties of stereolithographic 3D printed HAp bioceramic scaffold. Ceram Int. 2021;47:28924–31.

97.

Wang

Xie

Zhong

Wang

Rong

. 3D printed PCL/β-TCP cross-scale scaffold with high-precision fiber for providing cell growth and forming bones in the pores. Mater Sci Eng C Mater Biol Appl. 2021;127:112197.

98.

Ghosh

Pati

. Decellularized extracellular matrix and silk fibroin-based hybrid biomaterials: a comprehensive review on fabrication techniques and tissue-specific applications. Int J Biol Macromol. 2023;14:127410.

99.

Chang

Hung

Chiu

Chang

Yen

Liu

. Fabrication of elliptically constructed liquid crystalline elastomeric scaffolds for 3D artificial tissues. J Mech Behav Biomed Mater. 2023;146:106056.

100.

Farazin

Zhang

Gheisizadeh

Shahbazi

. 3D bio-printing for use as bone replacement tissues: a review of biomedical application. Biom Eng Adv. 2023;5:100075.

101.

Maihemuti

Zhang

Lin

Wang

Zhang

Jiang

. 3D-printed fish gelatin scaffolds for cartilage tissue engineering. Bioact Mater. 2023;26:77–87.

102.

Sagadevan

Schirhagl

Rahman

Ismail

Lett

Fatimah

Kaus

. Recent advancements in polymer matrix nanocomposites for bone tissue engineering applications. J Drug Deliv Sci Technol. 2023;82:104313.

103.

Zielińska

Karczewski

Eder

Kolanowski

Szalata

Wielgus

Szalata

Kim

Shin

Słomski

Souto

. Scaffolds for drug delivery and tissue engineering: The role of genetics. J Control Release. 2023;359:207–23.

104.

Dong

Leng

Guo

Cai

Zhu

Lin

. Adipose stem cells in tissue regeneration and repair: from bench to bedside. Regen Ther. 2023;24:547–60.

105.

Bharathi

Ganesh

Harini

Vatsala

Anushikaa

Aravind

Abinaya

Selvamurugan

. Chitosan-based scaffolds as drug delivery systems in bone tissue engineering. Int J Biol Macromol. 2022;222:132–53.

106.

Balasubramani

Jeganathan

Dinesh Kumar

. Numerical analysis of porosity effects on mechanical properties for tissue engineering scaffold. Mater Today Proc. 2023;30:124.

107.

Eskandani

Derakhshankhah

Jahanban-Esfahlan

Jaymand

. Biomimetic alginate-based electroconductive nanofibrous scaffolds for bone tissue engineering application. Int J Biol Macromol. 2023;249:125991.

108.

Janmohammadi

Nazemi

Salehi

AOM

Seyfoori

John

Nourbakhsh

Akbari

. Cellulose-based composite scaffolds for bone tissue engineering and localized drug delivery. Bioact Mater. 2023;20:137–63.

109.

Browning

Maclaren

Buenzli

Lanaro

Allenby

Woodruff

Simpson

. Model-based data analysis of tissue growth in thin 3D printed scaffolds. J Theor Biol. 2021;528:110852.

110.

Sakthiabirami

Kang

Jang

Soundharrajan

Lim

Yun

Park

Lee

Yang

Park

. Hybrid porous zirconia scaffolds fabricated using additive manufacturing for bone tissue engineering applications. Mater Sci Eng C Mater Biol Appl. 2021;123:111950.

111.

Liao

Han

Qian

. Review of a new bone tumor therapy strategy based on bifunctional biomaterials. Bone Research. 2021;9:18.

112.

Kirillova

Yeazel

Asheghali

Petersen

Dort

Gall

Becker

. Fabrication of biomedical scaffolds using biodegradable polymers. Chem Rev. 2021;121:11238–11304.

113.

Shanley

Mahon

Kelly

Dunne

. Harnessing the innate and adaptive immune system for tissue repair and regeneration: considering more than macrophages. Acta Biomater. 2021;133:208–21.

114.

González

Vlad

López

Aguado

. Novel bio-inspired 3D porous scaffold intended for bone-tissue engineering: design and in silico characterisation of histomorphometric, mechanical and mass-transport properties. Mater Des. 2023;225:111467.

115.

Jiang

Zhai

Luo

Chen

Deng

Wang

Chang

. A bifunctional biomaterial with photothermal effect for tumor therapy and bone regeneration. Adv Funct Mater. 2016;26:1197–1208.

116.

Chao

Wang

Min

Cao

Pan

Tan

. Effect of porosity on mechanical properties of porous tantalum scaffolds produced by electron beam powder bed fusion. Trans Nonferrous Met Soc China. 2022;32:2922–34.

117.

Singh

Batra

Kumar

Ahuja

Mahapatro

. Progress in bioactive surface coatings on biodegradable Mg alloys: a critical review towards clinical translation. Bioact Mater. 2023;19:717–57.

118.

Shi

Gao

Chen

Liu

Zhang

Wang

. Enhancement in mechanical and corrosion resistance properties of a biodegradable Zn-Fe alloy through second phase refinement. Mater Sci Eng C Mater Biol Appl. 2020;116:111197.

119.

Bakhtiari

Nouri

Khakbiz

Tolouei-Rad

. Fatigue behaviour of load-bearing polymeric bone scaffolds: a review. Acta Biomater. 2023;172:16–37.

120.

Salman

Schmauder

. Multiscale modeling of shape memory polymers foams nanocomposites. Comput Mater Sci. 2024;232:112658.

121.

Zhang

Cai

Liao

Deng

Vardhanabhuti

Ulery

Chen

Lin

. 4D printing of shape-memory polymeric scaffolds for adaptive biomedical implantation. Acta Biomater. 2021;122:101–10.

122.

Gomes

Teixeira

Ferraz

Prudêncio

Gomes

. Wound-healing peptides for treatment of chronic diabetic foot ulcers and other infected skin injuries. Molecules. 2017;22:1743.

123.

Deptuła

Zawrzykraj

Sawicka

Banach-Kopeć

Tylingo

Pikuła

. Application of 3D- printed hydrogels in wound healing and regenerative medicine. Biomed Pharmacother. 2023;167:115416.

124.

Yang

Ren

Liu

. N-halamine modified ceria nanoparticles: antibacterial response and accelerated wound healing application via a 3D printed scaffold. Compos B Eng. 2021;227:109390.

125.

Liu

Wang

Wei

Chen

Luo

. 3D printed hydrogel/PCL core/shell fiber scaffolds with NIR-triggered drug release for cancer therapy and wound healing. Acta Biomater. 2021;131:314–25.

126.

Wang

Zhang

Shi

Tan

Peng

Liu

Wang

. Rhubarb charcoal-crosslinked chitosan/silk fibroin sponge scaffold with efficient hemostasis, inflammation, and angiogenesis for promoting diabetic wound healing. Int J Biol Macromol. 2023;253:126796.

127.

Haki

Shamloo

Eslami

Mir-Mohammad-Sadeghi

Maleki

Hajizadeh

. Fabrication and characterization of an antibacterial chitosan-coated allantoin-loaded NaCMC/SA skin scaffold for wound healing applications. Int J Biol Macromol. 2023;253:127051.

128.

Cakmak

Ege

Yilmaz

Agturk

Dal Yontem

Enguven

Sarmis

Cakmak

Gunduz

Ege

. 3D printed styrax liquidus (Liquidambar orientalis Miller)-loaded poly (L-lactic acid)/chitosan based wound dressing material: fabrication, characterization, and biocompatibility results. Int J Biol Macromol. 2023;248:125835.

129.

Zhu

Zheng

Jiao

Nie

Song

Liu

Song

. Evaluation of inhibitory effects of geniposide on a tumor model of human breast cancer based on 3D printed Cs/Gel hybrid scaffold. Mater Sci Eng C Mater Biol Appl. 2021;119:111509.

130.

Shi

Hao

Zhang

Liu

Wang

. Insight into role and mechanism of Li on the key aspects of biodegradable Zn[sbnd]Li alloys: Microstructure evolution, mechanical properties, corrosion behavior and cytotoxicity. Mater Sci Eng C. 2020;114:111049.

131.

Liu

Meng

Volinsky

Zhang

Wang

. Influences of albumin on in vitro corrosion of pure Zn in artificial plasma. Corros Sci. 2019;153:341–56.

132.

Lan

Liang

Vyhlidal

Erkut

Kunze

Mulet-Sierra

Osswald

Ansari

Seikaly

Boluk

Adesida

. In vitro maturation and in vivo stability of bioprinted human nasal cartilage. J Tissue Eng. 2022;13:20417314221086368. doi:10.1177/20417314221086368.

133.

Beketov

Isaeva

Yakovleva

Demyashkin

Arguchinskaya

Kisel

Lagoda

Malakhov

Kharlov

Osidak

Domogatsky

. Bioprinting of cartilage with bioink based on high-concentration collagen and chondrocytes. Int J Mol Sci. 2021;22:11351.

134.

Liu

Hao

Chen

Zhang

Huang

Dai

Zhang

. 3D bioprinted neural tissue constructs for spinal cord injury repair. Biomaterials. 2021;272:120771.

135.

Wang

Zhang

Liu

Wang

Liu

Wang

. Chondrocyte-laden gelatin/sodium alginate hydrogel integrating 3D printed PU scaffold for auricular cartilage reconstruction. Int J Biol Macromol. 2023;253:126294.

136.

Bejleri

Robeson

Brown

Hunter

Maxwell

Streeter

Brazhkina

Park

Christman

Davis

. In vivo evaluation of bioprinted cardiac patches composed of cardiac-specific extracellular matrix and progenitor cells in a model of pediatric heart failure. Biomater Sci. 2022;10:444–56.

137.

Noor

Shapira

Edri

Gal

Wertheim

Dvir

. 3D printing of personalized thick and perfusable cardiac patches and hearts. Advanced Science. 2019;6:1900344.

138.

Cuvellier

Rose

Ezan

Jarry

de Oliveira

Bruyère

La Rochelle

Legagneux

Langouët

Baffet

. In vitro long term differentiation and functionality of three-dimensional bioprinted primary human hepatocytes: application for in vivo engraftment. Biofabrication. 2022;14:035021.

139.

Liu

Yang

Chen

Xie

Tai

Wang

. Three-dimensional bioprinting sodium alginate/gelatin scaffold combined with neural stem cells and oligodendrocytes markedly promoting nerve regeneration after spinal cord injury. Regen Biomater. 2022;9:rbac038.

140.

Lai

Chen

Zhou

Wang

Cui

Zhang

Wang

Liu

. Repair of infected bone defect with Clindamycin-Tetrahedral DNA nanostructure Complex-loaded 3D bioprinted hybrid scaffold. Chem Eng J. 2022;435:134855.

141.

Jiao

Liang

Zhao

Tian

Wang

Shen

. A tailored hydroxyapatite/magnesium silicate 3D composite scaffold: Mechanical, degradation, and bioactivity properties. Ceram Int. 2023;49:35438–47.

142.

Pecci

Baiguera

Ioppolo

Bedini

Del Gaudio

. 3D printed scaffolds with random microarchitecture for bone tissue engineering applications: manufacturing and characterization. J Mech Behav Biomed Mater. 2020;103:103583.

143.

Iviglia

Cassinelli

Bollati

Baino

Torre

Morra

Vitale-Brovarone

. Engineered porous scaffolds for periprosthetic infection prevention. Mater Sci Eng C. 2016;68:701–15.

144.

Cheng

Zhang

Liu

Zhang

Qian

Peng

. Osteogenesis, angiogenesis and immune response of Mg-Al layered double hydroxide coating on pure Mg. Bioact Mater. 2021;6(1):91–105.

145.

Soleymani

Naghib

. 3D and 4D printing hydroxyapatite-based scaffolds for bone tissue engineering and regeneration. Heliyon. 2023;9(9):e19363. doi:10.1016/j.heliyon.2023.e19363.

146.

Zhang

George

Petersen

Jimenez-Vergara

Hahn

Grunlan

. A bioactive “self-fitting” shape memory polymer scaffold with potential to treat cranio-maxillo facial bone defects. Acta Biomater. 2014;10(11):4597–4605.

147.

Mohapatra

Behera

Mishra

. Prospective of functionalized graphene as shape memory and self-healing polymer: a review. Mater Today Proc. Epub 2023 Jul 7. doi:10.1016/j.matpr.2023.06.389.

148.

Podgórski

Wojasi’nski

Ciach

. Pushing boundaries in 3D printing: Economic pressure filament extruder for producing polymeric and polymer-ceramic filaments for 3D printers. HardwareX. 2023;16:e00486. doi:10.17605/OSF.IO/X3FZN.

149.

Mobarak

Islam

Hossain

Al Mahmud

Rayhan

Nishi

Chowdhury

. Recent advances of additive manufacturing in implant fabrication—a review. Appl Surf Sci 2023;18:100462.

150.

Kazemi Asl

Rahimzadegan

Ostadrahimi

. The recent advancement in the chitosan hybrid-based scaffolds for cardiac regeneration after myocardial infarction. Carbohydrate Polymers. 2023;300:120266.

151.

Almeida

PHT

Cacciacane

Junior

. TEN-YEAR follow-up of treatment with zygomatic implants and replacement of hybrid dental prosthesis by ceramic teeth: a case report. Ann Med Surg. 2020;50:1–5.

152.

Shuai

Feng

Liu

Lai

Gao

Peng

. A combined nanostructure constructed by graphene and boron nitride nanotubes reinforces ceramic scaffolds. Chem Eng J. 2017;313:487–97.

153.

Lee

Kim

Yeo

Lee

Hwang

Lee

. Systematic evaluation of antibiotic activity of a cefazolin-loaded scaffold with varying 3D printing temperatures and its application in treating osteomyelitis. J Ind Eng Chem. 2023;124:539–49.

154.

Khan

Zheng

Cui

Zhang

. Protection properties of organosilane-epoxy coating on Al Alloy 6101 in alkaline solution. Surf Eng and App Electrochem. 2022;58:281–89.

155.

Chang

James

Qassab

Zhou

Ando

Shi

Zhang

. 3D chitosan scaffolds support expansion of human neural stem cells in chemically defined condition. Matter. 2023;6:3631–60.

156.

Fang

Kang

Cheng

Nie

Wang

Liu

Song

. A 3D bioprinted decellularized extracellular matrix/gelatin/quaternized chitosan scaffold assembling with poly(ionic liquid)s for skin tissue engineering. Int J Biol Macromol. 2022;220:1253–66.

157.

Kumar

Kritika

Karthikeyan

Sujatha

Mahalaxmi

Ravichandran

. Development of cobalt-incorporated chitosan scaffold for regenerative potential in human dental pulp stem cells: an in vitro study. Int J Biol Macromol. 2023;253:126574.

158.

Liao

Peng

Ning

Gao

Zhang

Sui

Lin

Liu

Hao

, et al. Chitosan hydrogel/3D-printed poly(ε-caprolactone) hybrid scaffold containing synovial mesenchymal stem cells for cartilage regeneration based on tetrahedral framework nucleic acid recruitment. Biomaterials. 2021;278:121131.

159.

Nedunchezian

Banerjee

Lee

Lin

Chang

Wang

. Generating adipose stem cell-laden hyaluronic acid-based scaffolds using 3D bioprinting via the double crosslinked strategy for chondrogenesis. Mater Sci Eng C Mater Biol Appl. 2021;124:112072.

160.

Zhong

Cao

Cheng

Tang

Sun

Song

. Investigation on repairing diabetic foot ulcer based on 3D bio-printing Gel/dECM/Qcs composite scaffolds. Tissue Cell. 2023;85:102213.

161.

Islam

Sadaf

Gómez

Mager

Korvink

Lantada

. Carbon fiber/microlattice 3D hybrid architecture as multi-scale scaffold for tissue engineering. Mater Sci Eng C Mater Biol Appl. 2021;126:112140.

162.

Young

Tallia

Clark

Chellappan

Gavalda-Diaz

Alcocer

Ferreira

Rankin

Clark

Hanna

Jeffers

. Hybrid materials with continuous mechanical property gradients that can be 3D printed. Mater Today Adv. 2023;17:100344.

163.

Liu

Miao

Liang

Diao

Hao

Shi

Zhao

Wang

. 3D-printed bioactive ceramic scaffolds with biomimetic micro/nano-HAp surfaces mediated cell fate and promoted bone augmentation of the bone–implant interface in vivo. Bioact Mater. 2022;12:120–32.

164.

Gao

Xie

Wang

Xie

Sun

. 3D printed multi-scale scaffolds with ultrafine fibers for providing excellent biocompatibility. Mater Sci Eng C Mater Biol Appl. 2020;107:110269.

165.

Liu

Zhang

Wang

Dong

Zhao

Sun

. 3D-printed porous PEEK scaffold combined with CSMA/POSS bioactive surface: a strategy for enhancing osseointegration of PEEK implants. Compos B Eng. 2022;230:109512.

166.

Kivijärvi

Goksøyr

Yassin

Jain

Yamada

Morales-López

Mustafa

Finne-Wistrand

. Hybrid material based on hyaluronan hydrogels and poly(L-lactide-co-1,3-trimethylene carbonate) scaffolds toward a cell-instructive microenvironment with long-term in vivo degradability. Mater Today Bio. 2022;17:100483.

167.

Topsakal

Midha

Yuca

Tukay

Sasmazel

Kalaskar

Gunduz

. Study on the cytocompatibility, mechanical and antimicrobial properties of 3D printed composite scaffolds based on PVA/ Gold nanoparticles (AuNP)/ Ampicillin (AMP) for bone tissue engineering. Mater Today Commun. 2021;28:102458.

168.

Grewal

Batra

Kumar

Mahapatro

. Novel PA encapsulated PCL hybrid coating for corrosion inhibition of biodegradable Mg alloys: a triple triggered self-healing response for synergistic multiple protection. J Magnes Alloys. 2023;11:1440–60.

169.

Khan

Altalbe

. Potential impacts of Russo-Ukraine conflict and its psychological consequences among Ukrainian adults: the post-COVID-19 era. Front Public Health. 2023;11:1280423.

170.

Khan

Grewal

Zhou

Kunshan

Zhang

Jun

. Recent advances in biodegradable metals for implant applications: Exploring in vivo and in vitro responses. Results in Engineering; 20. Epub Ahead of Print 1 December. 2023. doi:10.1016/j.rineng.2023.101526.

171.

Khan

Zhao

Zheng

. Composite fabrication of epoxy and graphene oxide coating to enrich the anticorrosion and thermal properties of carbon-steel. Surf Rev Lett. 2022;29:2250072.

172.

Zhao

Zhang

Tian

Wang

Zhao

Huang

. 3D printed epoxy/acrylate hybrid polymers with excellent mechanical and shape memory properties via UV and thermal cationic dual-curing mechanism. Addit Manuf. 2024;79:103904.

173.

Gréant

Van Durme

Van Damme

Brancart

Van Hoorick

Van Vlierberghe

. Digital light processing of poly(ε-caprolactone)-based resins into porous shape memory scaffolds. Eur Polym J. 2023;195:112225.

174.

Baker

Tseng

Iannolo

Oest

Henderson

. Self-deploying shape memory polymer scaffolds for grafting and stabilizing complex bone defects: a mouse femoral segmental defect study. Biomaterials. 2016;76:388–98.

175.

Arif

Khalid

Tariq

Hossain

Umer

. 3D printing of stimuli-responsive hydrogel materials: Literature review and emerging applications. Giant. 2024;17:100209. doi:10.1016/j.giant.2023.100209.

176.

Pandey

Mohol

Kandi

. 4D printing of tracheal scaffold using shape-memory polymer composite. Mater Lett. 2022;329:133238.

177.

Zhang

Chen

Liang

. 4D printing of multi-stimuli responsive rigid smart composite materials with self-healing ability. Chem Eng J. 2023;466:143420.

178.

Khalaj

Tabriz

Okereke

Douroumis

. 3D printing advances in the development of stents. Int J Pharm. 2021;609:121153.

179.

Wang

Han

Zhou

Cai

Sun

Wang

. The combination of a 3D-Printed porous Ti–6Al–4V alloy scaffold and stem cell sheet technology for the construction of biomimetic engineered bone at an ectopic site. Mater Today Bio. 2022;16:100433.

180.

Foroughi

Liu

Razavi

. Simultaneous optimization of stiffness, permeability, and surface area in metallic bone scaffolds. Int J Eng Sci. 2023;193:103961.

181.

Dave

Mahmud

Gomes

. Superhydrophilic 3D-printed scaffolds using conjugated bioresorbable nanocomposites for enhanced bone regeneration. Chem Eng J. 2022;445:136639.

Raising the Bar: Progress in 3D-Printed Hybrid Bone Scaffolds for Clinical Applications: A Review

Abstract

Keywords

Introduction

Critical Requirements for 3D Printed Scaffolds

The Mechanism for Repairing Bone Tissue

The Scaffold Structure Design Ensures Safety and Efficiency on Construction Sites

Tissue Engineering

Bone Scaffold Formation

Clinical Applications of 3D-printed Scaffolds

Wound and Infection Healing

Tumor Therapy

Cartilage and Spine Injury

Heart Disease and Liver Failure

Hybrid Scaffolds

Future Perspectives

Conclusion

Footnotes

Authors Contribution

Ethical Approval

Statement of Human and Animal Rights

Statement of Informed Consent

Declaration of Conflicting Interests

Funding

ORCID iD

References