Silk-based injectable photocurable hydrogel loaded with autologous growth factors for patient-specific repair of meniscal defects in vivo

Meniscus tears and injuries in the avascular region often lead to pain, swelling and locking of the knee joint due to the non-healing nature of fibrocartilaginous tissue. The current mandate of partial meniscectomy leads to osteoarthritis and loss of integrity of the knee joint. Stabilisation of the torn meniscal tissue must be achieved at the earliest to prevent damage to articular cartilage. We have developed a patient-specific facile approach in the form of a silk-based injectable hydrogel blend comprising of silk fibroin methacrylate, gelatin methacrylate, polyethylene glycol diacrylate and patient-derived autologous platelet-rich-plasma lysate for ameliorating meniscal tears. Our hydrogel could be crosslinked promptly within 60 s and demonstrated robust physicochemical and mechanical resilience in vitro. The injectable hydrogel demonstrated amicable shear thinning, optimal water uptake behaviour (similar to 1.2 times), sustained release of PRP proteins (>70 %) over 40 days and an intricate microporous architecture. We could observe sustained degradability (similar to 40 %) over 85 days under enzymatic conditions in vitro. Photocrosslinking imparts our hydrogel composition with physiologically relevant compressive strength and ample tensile strength to retain their position and aids in their stability over 3 weeks of confined cyclic compression cycles. Hydrogel-encapsulated human-derived neonatal mesenchymal stem cells showed >3 times proliferation, in vitro migration, fibrochondrogenic differentiation and meniscus-specific extracellular matrix deposition after 3 weeks. Our hydrogel demonstrated minimal in vitro immunogenicity when presented to murine and human macrophages. A pilot-scale in vivo evaluation in rabbit meniscal tears demonstrated the healing capacity of the injectable hydrogel composition in full-thickness tears of rabbit menisci compared to untreated counterparts after 8 weeks of treatment. Our patient-specific photopolymerisable injectable hydrogel could be a potential translational treatment modality for various partial and full-thickness meniscal tears in vivo.