Methacrylated gelatin and platelet-rich plasma based hydrogels promote regeneration of critical-sized bone defects

Shichao Lian; Zhiyu Mu; Zhengchao Yuan; Muhammad Shafiq; Xiumei Mo; Weidong Mu

doi:10.1093/rb/rbae022

Methacrylated gelatin and platelet-rich plasma based hydrogels promote regeneration of critical-sized bone defects

Regen Biomater. 2024 Mar 5:11:rbae022. doi: 10.1093/rb/rbae022. eCollection 2024.

Authors

Shichao Lian^{1

2}, Zhiyu Mu³, Zhengchao Yuan⁴, Muhammad Shafiq⁵, Xiumei Mo⁴, Weidong Mu¹

Affiliations

¹ Department of Traumatic Orthopaedics, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250012, China.
² Zoucheng People's Hospital, Zoucheng, Shandong 273500, China.
³ Department of Medical Physics and Biomedical Engineering, University of London, London WC1E 6BT, UK.
⁴ State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai 201620, PR China.
⁵ Innovation Center of NanoMedicine (iCONM), Kawasaki Institute of Industrial Promotion, Kawasaki-Ku, Kawasaki 210-0821, Japan.

Abstract

Physiological repair of large-sized bone defects requires instructive scaffolds with appropriate mechanical properties, biocompatibility, biodegradability, vasculogenic ability and osteo-inductivity. The objective of this study was to fabricate in situ injectable hydrogels using platelet-rich plasma (PRP)-loaded gelatin methacrylate (GM) and employ them for the regeneration of large-sized bone defects. We performed various biological assays as well as assessed the mechanical properties of GM@PRP hydrogels alongside evaluating the release kinetics of growth factors (GFs) from hydrogels. The GM@PRP hydrogels manifested sufficient mechanical properties to support the filling of the tissue defects. For biofunction assay, the GM@PRP hydrogels significantly improved cell migration and angiogenesis. Especially, transcriptome RNA sequencing of human umbilical vein endothelial cells and bone marrow-derived stem cells were performed to delineate vascularization and biomineralization abilities of GM@PRP hydrogels. The GM@PRP hydrogels were subcutaneously implanted in rats for up to 4 weeks for preliminary biocompatibility followed by their transplantation into a tibial defect model for up to 8 weeks in rats. Tibial defects treated with GM@PRP hydrogels manifested significant bone regeneration as well as angiogenesis, biomineralization, and collagen deposition. Based on the biocompatibility and biological function of GM@PRP hydrogels, a new strategy is provided for the regenerative repair of large-size bone defects.

Keywords: gelatin methacrylate; hydrogel; large-sized bone defect repair; platelet-rich plasma; tissue scaffold.