Sustained release of multicomponent platelet-rich plasma proteins from hydrolytically degradable PEG hydrogels

Platelet-rich plasma (PRP), an autologous blood derived product is a concentrated mix of multiple growth factors and cytokines. Direct injections of PRP are clinically used for treatment of various musculoskeletal disorders and in wound healing. However, PRP therapy has met with limited clinical success possibly due to unpredictable and premature bolus delivery of PRP growth factors. The objective of this study was to predictably control the bioavailability of PRP growth factors using a hydrolytically degradable polyethylene glycol (PEG) hydrogel. We used a step-growth polymerization based on a Michael-type addition reaction between a 6-arm PEG-acrylate and a dithiol crosslinker, which led to the formation of a homogenous hydrogel network under mild, physiologically relevant conditions. Specifically, to model the release of multicomponent PRP through PEG hydrogels, we examined bulk diffusion of PRP as well as model proteins in a size range corresponding to that of growth factors found in PRP. Our results indicated that protein size and hydrogel degradation controlled diffusion of all proteins and that secondary structure of proteins encapsulated during gelation remained unaffected post-release. Analysis of specific PRP proteins released from the hydrogel showed sustained release until complete hydrogel degradation. PRP released from hydrogels promoted proliferation of human dermal fibroblast, indicating retained bioactivity upon encapsulation and release. The versatile hydrogel system holds clinical potential as a therapeutic drug delivery depot of multicomponent mixtures like PRP.