Gelatin methacryloyl hydrogel loaded with injectable platelet-rich fibrin promotes skin wound repair

doi:10.12307/2025.588

Abstract

Abstract: BACKGROUND: Currently, gelatin methacryloyl and its composite materials are widely used in the field of skin wound repair, but single-function dressings only provide some passive protection and lack functions such as killing bacteria or regulating endogenous factors to promote skin wound healing. Injectable platelet-rich fibrin contains high concentrations of cytokines, which can promote skin wound healing.
OBJECTIVE: To observe the effect of gelatin methacryloyl hydrogel loaded with injectable platelet-rich fibrin on skin wound healing.
METHODS: (1) Injectable platelet-rich fibrin was isolated and extracted from rat venous blood. Gelatin methacryloyl/injectable platelet-rich fibrin hydrogel (denoted as GelMA/i-PRF hydrogel) was prepared by mixing equal volumes of gelatin methacryloyl and injectable platelet-rich fibrin. At the same time, pure gelatin methacryloyl hydrogel (denoted as GelMA hydrogel) was prepared. The morphology, swelling and degradation properties of the hydrogel were characterized. Staphylococcus aureus (or Escherichia coli) were inoculated on the surface of GelMA hydrogel and GelMA/i-PRF hydrogel to detect the antibacterial properties of the hydrogel. L929 cells were inoculated on the surface of the two hydrogels. The cell proliferation, viability, and migration ability were detected by CCK-8 assay, live/dead cell staining, and scratch test. (2) A full-thickness skin defect with a diameter of 10 mm was made on the back of 9 SD rats. They were randomly divided into three groups for intervention. The control group was injected with PBS at the defect site, and the other two groups were injected with GelMA hydrogel and GelMA/i-PRF hydrogel at the defect site, respectively. The wound healing was observed within 11 days after surgery. The samples were taken for hematoxylin-eosin and Sirius red staining 11 days later.
RESULTS AND CONCLUSION: (1) GelMA/i-PRF hydrogel had a good pore structure with an average pore size of (111.4±10.4) µm. The surface roughness and swelling rate were greater than those of GelMA hydrogel, and the degradation performance was not significantly different from that of GelMA hydrogel. Compared with GelMA/hydrogel, GelMA/i-PRF hydrogel had stronger antibacterial ability, could promote L929 cell proliferation, and improve cell viability and migration ability. (2) Compared with GelMA/hydrogel, GelMA/i-PRF hydrogel can promote the healing of rat skin wounds and improve the quality of skin wound healing. (3) Gelatin methacryloyl/injectable platelet-rich fibrin hydrogel can accelerate the healing of skin wounds by promoting the proliferation and migration of skin fibroblasts, and improve the quality of skin wound healing.

Key words: composite hydrogel, injectable platelet-rich fibrin, gelatin methacryloyl, wound dressing, skin tissue engineering, engineered skin material

CLC Number:

Wei Dongdong, Shi Meikun, Wang Lei. Gelatin methacryloyl hydrogel loaded with injectable platelet-rich fibrin promotes skin wound repair[J]. Chinese Journal of Tissue Engineering Research, 2026, 30(14): 3643-3651.

Figures/Tables 12

References

[1] LIANG C, HE J, CAO Y, et al. Advances in the application of Mxene nanoparticles in wound healing. J Biol Eng. 2023;17(1):39.
[2] XU C, ZHANG Y, LI H, et al. Carboxymethylated yeast β-glucan: Biological activity screening in zebrafish, sprayable hydrogel preparation, and wound healing study in diabetic mice. Int J Biol Macromol. 2024;285: 138178.
[3] ZHANG W, LIU W, LONG L, et al. Responsive multifunctional hydrogels emulating the chronic wounds healing cascade for skin repair. J Control Release. 2023;354:821-834.
[4] GE X, HU J, QI X, et al. An Immunomodulatory Hydrogel Featuring Antibacterial and Reactive Oxygen Species Scavenging Properties for Treating Periodontitis in Diabetes. Adv Mater. 2024:e2412240. doi:10.1002/adma.202412240.
[5] VAN DEN BULCKE AI, BOGDANOV B, DE ROOZE N, et al. Structural and rheological properties of methacrylamide modified gelatin hydrogels. Biomacromolecules. 2000;1(1):31-38.
[6] DO NASCIMENTO MF, DE OLIVEIRA CR, CARDOSO JC, et al. UV-polymerizable methacrylated gelatin (GelMA)-based hydrogel containing tannic acids for wound healing. Drug Deliv Transl Res. 2023;13(12):3223-3238.
[7] AUBIN H, NICHOL JW, HUTSON CB, et al. Directed 3D cell alignment and elongation in microengineered hydrogels. Biomaterials. 2010; 31(27):6941-6951.
[8] NIKKHAH M, ESHAK N, ZORLUTUNA P, et al. Directed endothelial cell morphogenesis in micropatterned gelatin methacrylate hydrogels. Biomaterials. 2012;33(35):9009-9018.
[9] FU C, QI Z, ZHAO C, et al. Enhanced wound repair ability of arginine-chitosan nanocomposite membrane through the antimicrobial peptides-loaded polydopamine-modified graphene oxide. J Biol Eng. 2021;15(1):17.
[10] LIANG C, WANG H, LIN Z, et al. Augmented wound healing potential of photosensitive GelMA hydrogel incorporating antimicrobial peptides and MXene nanoparticles. Front Bioeng Biotechnol. 2023;11:1310349.
[11] TIAN K, YE J, ZHONG Y, et al. Autologous i-PRF promotes healing of radiation-induced skin injury. Wound Repair Regen. 2023;31(4): 454-463.
[12] DOHAN DM, CHOUKROUN J, DISS A, et al. Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part II: platelet-related biologic features. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101(3):e45-50.
[13] OZSAGIR ZB, SAGLAM E, SEN YILMAZ B, et al. Injectable platelet-rich fibrin and microneedling for gingival augmentation in thin periodontal phenotype: A randomized controlled clinical trial. J Clin Periodontol. 2020;47(4):489-499.
[14] SALEH W, ABDELHALEEM M, ELMEADAWY S. Assessing the effectiveness of advanced platelet rich fibrin in treating gingival recession: a systematic review and meta-analysis. BMC Oral Health. 2024;24(1):1400.
[15] ŞEN DÖ, ŞENGÜL BI, YARKAÇ FU, et al. Impact of platelet-rich fibrin derivatives on patient morbidity and quality of life in palatal donor sites following free gingival graft surgery: a randomized clinical trial. Clin Oral Investig. 2024;28(12):631.
[16] GHADGE KK, SHETTY SK, KHARAT A, et al. Translational implications of a novel combination of iPRF and collagen scaffold for proliferation of gingival mesenchymal stem cells. Sci Rep. 2024;14(1):27789.
[17] GHANAATI S, BOOMS P, ORLOWSKA A, et al. Advanced platelet-rich fibrin: a new concept for cell-based tissue engineering by means of inflammatory cells. J Oral Implantol. 2014;40(6):679-689.
[18] ZENG R, XIONG Y, LIN Z, et al. Novel cocktail therapy based on multifunctional supramolecular hydrogel targeting immune-angiogenesis-nerve network for enhanced diabetic wound healing. J Nanobiotechnology. 2024;22(1):749.
[19] FUJIOKA-KOBAYASHI M, KATAGIRI H, KONO M, et al. Improved growth factor delivery and cellular activity using concentrated platelet-rich fibrin (C-PRF) when compared with traditional injectable (i-PRF) protocols. Clin Oral Investig. 2020;24(12):4373-4383.
[20] ZHANG W, LI Z, ZHANG Q, et al. Ionic conducting hydrogels as biomedical materials: classification, design strategies, and skin tissue engineering applications. J Biomater Sci Polym Ed. 2024:1-24. doi: 10.1080/09205063.2024.2434300.
[21] ALI EM, RAJENDRAN P, ABDALLAH BM. Mycosynthesis of silver nanoparticles from endophytic Aspergillus parasiticus and their antibacterial activity against methicillin-resistant Staphylococcus aureus in vitro and in vivo. Front Microbiol. 2024;15:1483637.
[22] WANG J, WANG W, LI K, et al. A functional hydrogel dressing based on glycyrrhizic acid with low-swelling and moisturizing properties for enhancing infected wound repair. J Mater Chem B. 2024. doi: 10.1039/d4tb01572j.
[23] EGLE K, SKADINS I, GRAVA A, et al. Injectable Platelet-Rich Fibrin as a Drug Carrier Increases the Antibacterial Susceptibility of Antibiotic-Clindamycin Phosphate. Int J Mol Sci. 2022;23(13):7407.
[24] CL K, JEYARAMAN M, JEYARAMAN N, et al. Antimicrobial Effects of Platelet-Rich Plasma and Platelet-Rich Fibrin: A Scoping Review. Cureus. 2023;15(12):e51360.
[25] LIU T, HAO J, LEI H, et al. Recombinant collagen for the repair of skin wounds and photo-aging damage. Regen Biomater. 2024;11:rbae108.
[26] WEI J, WANG B, WANG H, et al. Radiation-Induced Normal Tissue Damage: Oxidative Stress and Epigenetic Mechanisms. Oxid Med Cell Longev. 2019;2019:3010342.
[27] DUNNILL C, PATTON T, BRENNAN J, et al. Reactive oxygen species (ROS) and wound healing: the functional role of ROS and emerging ROS-modulating technologies for augmentation of the healing process. Int Wound J. 2017;14(1):89-96.
[28] ZHAO Y, CHEN J, ZHOU M, et al. Desferrioxamine-Laden Nanofibrous Scaffolds with Efficient Angiogenesis for Accelerating Diabetic Wound Healing. Int J Nanomedicine. 2024;19:10551-10568.
[29] DING L, LIN H, YANG Z, et al. Polycaprolactone/gelatin-QAS/bioglass nanofibres accelerate diabetic chronic wound healing by improving dysfunction of fibroblasts. Int J Biol Macromol. 2024;283(Pt 2): 136699.
[30] ANWAR MA, EL GEDAILY RA, SALAMA A, et al. Phytochemical analysis and wound healing properties of Malva parviflora L. ethanolic extract. J Ethnopharmacol. 2025;337(Pt 3):118983.
[31] NING X, WANG R, LIU N, et al. Three-dimensional structured PLCL/ADM bioactive aerogel for rapid repair of full-thickness skin defects. Biomater Sci. 2024;12(24):6325-6337.
[32] KIM J, JEONG SH, THIBAULT BC, et al. Large Scale Ultrafast Manufacturing of Wireless Soft Bioelectronics Enabled by Autonomous Robot Arm Printing Assisted by a Computer Vision-Enabled Guidance System for Personalized Wound Healing. Adv Healthc Mater. 2024: e2401735. doi: 10.1002/adhm.202401735.
[33] REHMAN SRU, AUGUSTINE R, ZAHID AA, et al. Reduced Graphene Oxide Incorporated GelMA Hydrogel Promotes Angiogenesis For Wound Healing Applications. Int J Nanomedicine. 2019;14: 9603-9617.