Multifunctional Integrated Hydrogels for Tissue Regeneration and Repair

Abstract

Multifunctional integrated hydrogels have emerged as advanced biomaterials that integrate diverse functional properties, including bioactivity, mechanical adaptability, controlled drug release, and electrical/magnetic responsiveness, exhibiting substantial potential in tissue regeneration and repair. These hydrogels provide a versatile platform to mimic the complex microenvironment of native tissues, thereby facilitating cell proliferation, differentiation, and tissue remodeling. Despite rapid progress in their design and development, optimizing performance for specific tissues (e.g., bone, cartilage, skin, nerve, myocardium) remains challenging. Current research focuses on innovative design strategies and the incorporation of key functional modules to tailor hydrogels for targeted regenerative applications. Moreover, translating these materials from bench to bedside requires overcoming barriers related to biocompatibility, scalability, regulatory approval, and long-term functional stability. This review comprehensively summarizes recent advances in multifunctional integrated hydrogels, highlights their applications across different tissue regeneration scenarios, and critically evaluates translational challenges. By synthesizing cutting-edge findings, this work aims to guide the development of next-generation smart tissue engineering scaffolds and accelerate their clinical adoption, ultimately advancing regenerative medicine.

Impact Statement

This review systematically and critically synthesizes the latest advances in multifunctional integrated hydrogels for tissue regeneration and repair, filling a key knowledge gap in the field by integrating modular design principles, core functional mechanisms, and translational challenges of these advanced biomaterials across major tissue types (bone, cartilage, skin, nerve, myocardium). By collating cutting-edge findings in material design, biological functionality, and tissue-specific applications, it establishes a unified theoretical framework for interdisciplinary researchers in materials science, bioengineering, and regenerative medicine and offers actionable guidance for the rational design of next-generation smart hydrogel scaffolds tailored to the dynamic biological demands of tissue healing. Beyond basic research insights, this work identifies and analyzes core translational bottlenecks, including biocompatibility evaluation, scalable clinical-grade manufacturing, and regulatory approval for combination biomaterials, and proposes practical strategies to address these barriers, thereby bridging fundamental hydrogel research and clinical practice. It also provides a scientific basis for clinicians to understand the therapeutic potential of hydrogel biomaterials in tissue repair and offers reference criteria for regulatory agencies to formulate evaluation standards for multifunctional biomaterial combination products. The review highlights the transformative potential of multifunctional integrated hydrogels in regenerative medicine, from personalized tissue scaffolds via three-dimensional/four-dimensional bioprinting to adaptive closed-loop treatment systems, and underscores the necessity of interdisciplinary collaboration among material scientists, biologists, clinicians, and industry partners. In doing so, it accelerates the clinical translation of hydrogel-based tissue engineering technologies, provides novel and effective biomaterial solutions for patients with tissue damage and functional loss, and drives the overall development of regenerative medicine with practical research and clinical value. The research perspectives and translational strategies presented herein deliver valuable research insights for the global advancement of smart biomaterials, contributing to the development of international tissue engineering and regenerative medicine research.