Human Platelet Lysate-functionalized Hydrogels - A Novel Solution for Bone Regeneration

Abstract

Introduction Critical-size bone defects challenge bone regeneration, impacting healing and functional outcomes. Bone implants address these issues, but ttheir bio integration is complicated by increased defect sizes and their impact on biological processes, such as the transport of vital nutrients, and cell ingrowth.[1] This study focused on the development of bio-functionalised hydrogels based on modified Human Platelet Lysate (PL), which could potentially improve osseointegration of 3D-printed bone scaffolds. Experimental Methods After the modification of PL with photopolymerizable groups (i.e. allyl glycidyl ether (PLAGE)), the novel material was crosslinked using photopolymerization and its properties were compared to similar gelatin systems. Extensive in situ photorheology, swelling tests and in vitro studies enabled detailed characterization of the hydrogels. Preliminary in vivo tests also provided insight on the hydrogel’s performance in the living organism. Results and Discussion Various photocrosslinkable PL alternatives were synthesized and subsequently crosslinked. Crosslinking photopolymerizable motifs in the material's modified backbone allowed for the improvement of the unmodified lysates' poor mechanical properties. Noteworthy, hydrogel formation was observed in presence and in absence of thiols. Thiol groups in the protein backbone enhanced gel formation in PL, which is primarily based on serum albumin and has cysteine as its most prevalent amino acid. Since this project was focused on the development of hydrogels which may help artificial bone scaffolds produced by 3D printing integrate better, the material’s applicability in Tissue Engineering & Regenerative Medicine was investigated. An in vivo pilot test on dorsal subcutaneous mouse model was conducted for the most promising PL-based hydrogels, to evaluate the acute response, grade of inflammation, and degradation. Conclusions A promising versatile PL-based hydrogel platform was established for potentially improved osseointegration of artificial bone implants. Different crosslinking approaches were evaluated and the resulting mechanical properties were screened. By altering the parameters, a promising system for 3D biofabrication can be developed. Overall, this novel material platform exhibited promising results for bone tissue engineering.