The Controlled Release of Platelet-Rich Plasma-Loaded Alginate Repairs Muscle Damage With Less Fibrosis.

Abstract

Muscle injuries often result in dysfunctional muscle repair and reduced muscle strength. While platelet-rich plasma (PRP) has emerged as a new treatment option in orthopaedics, its use for muscle injuries remains controversial. Encapsulating PRP within alginate hydrogels will achieve a localized and sustained release of growth factors at the site of the muscle injury, thereby enhancing skeletal muscle repair and reducing fibrosis. Controlled laboratory study. Bimodal blends of hydrogels were formulated using 1% oxidized high- and low-molecular weight alginate. There were 2 types of PRP prepared: leukocyte-rich PRP (L-PRP) and pure PRP (P-PRP). These PRP types were loaded onto 75L25H alginate hydrogels, and the release of TGF-β1 was quantified over time. A laceration injury was induced in mice, which was then treated with various agents: alginate only, L-PRP, L-PRP-loaded alginate (L-PRPA), P-PRP, and P-PRP-loaded alginate (P-PRPA). An additional 2 groups were formed: injury with no treatment and control with no treatment or injury. Our in vitro experiments showed that after an initial burst, TGF-β1 was released in a sustained manner for approximately 1 week after the encapsulation of both PRP preparations. The in vivo experiments showed that the groups treated with bolus injections of L-PRP or P-PRP did not show significant changes in the fibrotic area. However, the L-PRPA and P-PRPA groups demonstrated a 50% reduction in the fibrotic area (<i>P</i> < .05), resulting in a higher ratio of regenerating myofibers and higher levels of myogenic markers (myogenin and MyHC-emb) compared with all the other groups (<i>P</i> < .05). The L-PRPA group demonstrated significantly improved performance on the rotarod test; interestingly, this group also had more type I collagen than type III collagen. The administration of L-PRP and P-PRP after a muscle injury did not reduce fibrosis. However, when loaded onto alginate hydrogels, they led to benefits, resulting in a smaller area of fibrosis and greater tissue regeneration. The encapsulation of different preparations of PRP by alginate hydrogels was more effective in treating muscle lacerations than injections of PRP alone. This information is relevant for future clinical studies of PRP.