Effective drug delivery to target sites is critical for achieving desired therapeutic outcomes. However, the poor permeability of certain drugs poses significant challenges in achieving adequate drug concentrations at the desired locations. Biomimetic hydrogels have emerged as a promising approach to enhance the penetration of poorly permeable drugs. These hydrogels, designed to mimic natural biological systems, offer unique properties and functionalities that enable improved drug permeation. In this review, we provide a comprehensive appraisal of the role of biomimetic hydrogels in enhancing drug penetration. We discuss the design principles, properties, and mechanisms by which these hydrogels facilitate drug permeation. Specifically, we explore the applications and benefits of biomimetic hydrogels in controlled drug release, mimicking extracellular matrix microenvironments, promoting cell-mimetic interactions, and enabling targeted drug delivery. Through an examination of key studies and advancements, we highlight the potential of biomimetic hydrogels in enhancing drug penetration and their implications for therapeutic interventions. This review contributes to a deeper understanding of biomimetic hydrogels as a promising strategy for overcoming drug penetration challenges and advancing drug delivery systems, ultimately leading to improved therapeutic efficacy.
RichbourgNR, PeppasNA, SikavitsasVI. Tuning the biomimetic behavior of scaffolds for regenerative medicine through surface modifications. J Tissue Eng Regen Med, 2019; 13(8):1275–1293; doi: 10.1002/term.2859
3.
KamataH, LiX, ChungUI, et al.Design of hydrogels for biomedical applications. Adv Healthc Mater, 2015; 4(16):2360–2374; doi: 10.1002/adhm.201500076
4.
ZhangS. Fabrication of novel biomaterials through molecular self-assembly. Nat Biotechnol, 2003; 21(10):1171–1178; doi: 10.1038/nbt874
5.
ChaudhuriO, GuL, KlumpersD, et al.Hydrogels with tunable stress relaxation regulate stem cell fate and activity. Nat Mater, 2016; 15(3):326–334; doi: 10.1038/nmat4489
6.
LeeKY, RowleyJA, EiseltP, et al.Controlling mechanical and swelling properties of alginate hydrogels independently by cross-linker type and cross-linking density. Macromolecules, 2000; 33(11):4291–4294; doi: 10.1021/ma9921347
7.
WangX, YanY, PanY, et al.Fabrication of highly aligned collagen scaffolds by freeze-drying followed by hydrothermal treatment. J Biomed Mater Res A, 2010; 93(2):843–851; doi: 10.1021/acsbiomaterials.6b00036
8.
GongC, WuQ, WangY, et al.A biodegradable hydrogel system containing curcumin encapsulated in micelles for cutaneous wound healing. Biomaterials, 2013; 34(27):6377–6387; doi: 10.1016/j.biomaterials.2013.05.005
9.
HuangS, FuX. Naturally derived materials-based cell and drug delivery systems in skin regeneration. J Control Rel, 2010; 142(2):149–159; doi: 10.1016/j.jconrel.2009.10.018
10.
KharkarPM, KiickKL, KloxinAM. Designing degradable hydrogels for orthogonal control of cell microenvironments. Chem Soc Rev, 2013; 42(17):7335–7372; doi: 10.1039/C3CS60040H
11.
ZhaoX, LangQ, YildirimerL, et al.Photothermal-responsive nanosized hybrid polymersome as versatile therapeutics codelivery nanovehicle for effective tumor suppression. Small, 2014; 10(17):3464–3476; doi: 10.1073/pnas.1817251116
12.
BriquezPS, HubbellJA, MartinoMM. Extracellular matrix-inspired growth factor delivery systems for skin wound healing. Adv Wound Care (New Rochelle), 2015; 4(8):479–489; doi: 10.1089/wound.2014.0603
13.
SanejaA, KumarR, AroraD, et al.Recent advances in near-infrared light-responsive nanocarriers for cancer therapy. Drug Discov Today, 2018; 23(5):1115–1125; doi: 10.1016/j.drudis.2018.02.005
14.
AkagiT, NaguraM, HiuraA, et al.Construction of three-dimensional dermo–Epidermal skin equivalents using cell coating technology and their utilization as alternative skin for permeation studies and skin irritation tests. Tissue Eng A, 2017; 23(11–12):481–490; doi: 10.1089/ten.tea.2016.0529
15.
Sánchez-MoránH, AhmadiA, VoglerB, et al.Oxime cross-linked alginate hydrogels with tunable stress relaxation. Biomacromolecules, 2019; 20(12):4419–4429; doi: 10.1021/acs.biomac.9b01100
16.
PeppasNA, HiltJZ, KhademhosseiniA, et al.Hydrogels in biology and medicine: From molecular principles to bionanotechnology. Adv Mater, 2006; 18(11):1345–1360; doi: 10.1002/adma.200501612
AnnabiN, TamayolA, UquillasJA, et al.25th Anniversary Article: Rational design and applications of hydrogels in regenerative medicine. Adv Mater, 2014; 26(1):85–124.
19.
HoffmanAS. Hydrogels for biomedical applications. Adv Drug Deliv Rev, 2012; 64:18–23; doi: 10.1016/j.addr.2012.09.010
20.
StuartMAC, HuckWTS, GenzerJ, et al.Emerging applications of stimuli-responsive polymer materials. Nat Mater, 2010; 9(2):101–113; doi: 10.1038/nmat2614
21.
CensiR, Di MartinoP, VermondenT, et al.Hydrogels for protein delivery in tissue engineering. J Control Release, 2012; 161(2):680–692; doi: 10.1016/j.jconrel.2012.03.002
22.
TibbittMW, AnsethKS. Hydrogels as extracellular matrix mimics for 3D cell culture. Biotechnol Bioeng, 2009; 103(4):655–663; doi: 10.1002/bit.22361
23.
CaliariSR, BurdickJA. A practical guide to hydrogels for cell culture. Nat Methods, 2016; 13(5):405–414; doi: 10.1038/nmeth.3839
24.
DruryJL, MooneyDJ. Hydrogels for tissue engineering: Scaffold design variables and applications. Biomaterials, 2003; 24(24):4337–4351; doi: 10.1016/S0142-9612(03)00340-5
25.
BaroliB. From natural bone grafts to tissue engineering therapeutics: Brainstorming on pharmaceutical formulative requirements and challenges. J Pharm Sci, 2009; 98(4):1317–1375; doi: 10.1002/jps.21528
El-SherbinyIM, YacoubMH. Hydrogel scaffolds for tissue engineering: Progress and challenges. Glob Cardiol Sci Pract, 2013; 3:316–342; doi: 10.5339/gcsp.2013.38
28.
PlaceES, EvansND, StevensMM. Complexity in biomaterials for tissue engineering. Nat Mater, 2009; 8(6):457–470; doi: 10.5339/gcsp.2013.38
29.
D'AmicoF, SkarmoutsouE, StivalaF. State of the art in antigen retrieval for immunohistochemistry. J Immunol Methods, 2009; 341(1–2):1–18; doi: 10.1016/j.jim.2008.11.007
30.
RatnerBD, BryantSJ. Biomaterials: Where we have been and where we are going. Annu Rev Biomed Eng, 2004; 6:41–75; doi: 10.1146/annurev.bioeng.6.040803.140027
31.
LangerR. Biomaterials in drug delivery and tissue engineering: One laboratory's experience. Acc Chem Res, 2000; 33(2):94–101; doi: 10.1021/ar9800993
32.
HorcajadaP, ChalatiT, SerreC, et al.Porous metal–organic-framework nanoscale carriers as a potential platform for drug delivery and imaging. Nat Mater, 2010; 9(2):172–178; doi: 10.1038/nmat2608
SchmaljohannD. Thermo- and pH-responsive polymers in drug delivery. Adv Drug Deliv Rev, 2006; 58(15):1655–1670; doi: 10.1016/j.addr.2006.09.020
35.
HuangX, WangY, WangT, et al.Recent advances in engineering hydrogels for niche biomimicking and hematopoietic stem cell culturing. Front Bioeng Biotechnol, 2022; 10:1049965; doi: 10.3389/fbioe.2022.1049965
36.
ZhuW, ZhangJ, WeiZ, et al.Advances and progress in self-healing hydrogel and its application in regenerative medicine. Materials, 2023; 16(3):1215; doi: 10.3390/ma16031215.
37.
MorelloG, De IacoG, GigliG, et al.Chitosan and pectin hydrogels for tissue engineering and in vitro modeling. Gels, 2023; 9(2):132; doi: 10.3390/gels9020132
38.
Asim RazaM, ShahzadK, Dutt PurohitS, et al.The fabrication strategies for chitosan/poly (vinyl pyrrolidone) based hydrogels and their biomedical applications: A focused review. Polym Plast Tech Mat, 2023; 62:1–7; doi: 10.1080/25740881.2023.2252928
39.
KimYE, JungHY, ParkN, et al.Adhesive composite hydrogel patch for sustained transdermal drug delivery to treat atopic dermatitis. Chem Mater, 2023; 35(3):1209–1217; doi: 10.1021/acs.chemmater.2c03234
40.
ChenP, LiaoX. Kartogenin delivery systems for biomedical therapeutics and regenerative medicine. Drug Dev, 2023; 30(1):2254519; doi: 10.1080/10717544.2023.2254519
41.
SelvamA, MajoodM, ChaurasiaR, et al.Injectable organo-hydrogels influenced by click chemistry as a paramount stratagem in the conveyor belt of pharmaceutical revolution. J Mater Chem B, 2023 [Online ahead of print]; doi: 10.1039/D3TB01674A
42.
GanesonK, Tan Xue MayC, AbdullahAA, et al.Advantages and prospective implications of smart materials in tissue engineering: Piezoelectric, shape memory, and hydrogels. Pharmaceutics, 2023; 15(9):2356; doi: 10.3390/pharmaceutics15092356
43.
ConstantinoVR, FigueiredoMP, MagriVR, et al.Biomaterials based on organic polymers and layered double hydroxides nanocomposites: Drug delivery and tissue engineering. Pharmaceutics, 2023; 15(2):413; doi: 10.3390/pharmaceutics15020413
44.
KuznetsovaTA, AndryukovBG, BesednovaNN, et al.Marine algae polysaccharides as basis for wound dressings, drug delivery, and tissue engineering: A review. J Mar Sci Eng, 2020; 8(7):481; doi: 10.3390/jmse8070481
45.
SoodA, GuptaA, AgrawalG. Recent advances in polysaccharides based biomaterials for drug delivery and tissue engineering applications. Carbohydr Polym Technol Appl, 2021; 2:100067; doi: 10.1016/j.carpta.2021.100067
46.
KumarR, ButreddyA, KommineniN, et al.Lignin: Drug/gene delivery and tissue engineering applications. Int J Nanomed, 2021; 16:2419–2441; doi: 10.2147/IJN.S303462
47.
ElkhouryK, RussellCS, Sanchez-GonzalezL, et al.Soft-nanoparticle functionalization of natural hydrogels for tissue engineering applications. Adv Healthc Mater, 2019; 8(18):1900506; doi: 10.1002/adhm.201900506
48.
PatelS, AthirasalaA, MenezesPP, et al.Messenger RNA delivery for tissue engineering and regenerative medicine applications. Tissue Eng Part A, 2019; 25(1–2):91–112; doi: 10.1089/ten.tea.2017.0444
49.
LeeV, SinghG, TrasattiJP, et al.Design and fabrication of human skin by three-dimensional bioprinting. Tissue Eng Part C Methods, 2014; 20(6):473–484; doi: 10.1089/ten.TEC.2013.0335
50.
MaL, GaoC, MaoZ, et al.Collagen/chitosan porous scaffolds with improved biostability for skin tissue engineering. Biomaterials, 2003; 24(26):4833–4841; doi: 10.1016/S0142-9612(03)00374-0
VarkeyM, DingJ, TredgetEE. Advances in skin substitutes—Potential of tissue engineered skin for facilitating anti-fibrotic healing. J Funct Biomater, 2015; 6(3):547–563; doi: 10.3390/jfb6030547
53.
ZhangY, OuyangH, LimCT, et al.Electrospinning of gelatin fibers and gelatin/PCL composite fibrous scaffolds. J Biomed Mater Res B Appl Biomater, 2005; 72(1):156–165; doi: 10.1002/jbm.b.30128
54.
MurphySV, SkardalA, AtalaA. Evaluation of hydrogels for bio-printing applications. J Biomed Mater Res A, 2013; 101(1):272–284; doi: 10.1002/jbm.a.34302
55.
PereiraRF, SousaA, BarriasCC, et al.A single-component hydrogel bioink for bioprinting of bioengineered 3D constructs for dermal tissue engineering. Mater Horiz, 2018; 5(6):1100–1111; doi: 10.1039/C8MH00525G
56.
QuJ, ZhaoX, LiangY, et al.Antibacterial adhesive injectable hydrogels with rapid self-healing, extensibility and compressibility as wound dressing for joints skin wound healing. Biomaterials, 2018; 183:185–199; doi: 10.1016/j.biomaterials.2018.08.045
57.
Gholipour-KananiA, BahramiSH, JoghataieMT, et al.Preparation and evaluation of novel nano-bioglass/gelatin conduit for peripheral nerve regeneration. J Mater Sci Mater Med, 2013; 24(2):387–398; doi: 10.1007/s10856-013-5076-1
58.
ChaudhariAA, VigK, BaganiziDR, et al.Future prospects for scaffolding methods and biomaterials in skin tissue engineering: A review. Int J Mol Sci, 2016; 17(12):1974; doi: 10.3390/ijms17121974
59.
SunBK, SiprashviliZ, KhavariPA. Advances in skin grafting and treatment of cutaneous wounds. Science, 2014; 346(6212):941–945; doi: 10.1126/science.1253836
60.
LongX, XuX, SunD, et al.Biomimetic macroporous hydrogel with a triple-network structure for full-thickness skin regeneration. Appl Mater Today, 2022; 27:101442 doi: 10.1016/j.apmt.2022.101442
61.
SkardalA, MackD, KapetanovicE, et al.Bioprinted amniotic fluid-derived stem cells accelerate healing of large skin wounds. Stem Cells Transl Med, 2012; 1(11):792–802; doi: 10.5966/sctm.2012-0088
