Injectable recombinant block polymer gel for sustained delivery of therapeutic protein in post traumatic osteoarthritis

Protein-based biomaterials offer several advantages over synthetic materials, owing to their unique stimuliresponsive properties, biocompatibility and modular nature. Here, we demonstrate that E5C, a recombinant protein block polymer, consisting of five repeats of elastin like polypeptide (E) and a coiled-coil domain of cartilage oligomeric matrix protein (C), is capable of forming a porous networked gel at physiological temperature, making it an excellent candidate for injectable biomaterials. Combination of E5C with Atsttrin, a chondroprotective engineered derivative of anti-inflammatory growth factor progranulin, provides a unique biochemical and biomechanical environment to protect against post-traumatic osteoarthritis (PTOA) onset and progression. E5C gel was demonstrated to provide prolonged release of Atsttrin and inhibit chondrocyte catabolism while facilitating anabolic signaling in vitro. We also provide in vivo evidence that prophylactic and therapeutic application of Atsttrin-loaded E5C gels protected against PTOA onset and progression in a rabbit anterior cruciate ligament transection model. Collectively, we have developed a unique protein-based gel capable of minimally invasive, sustained delivery of prospective therapeutics, particularly the progranulinderivative Atsttrin, for therapeutic application in OA.

Automated summary

Protein-based biomaterials, such as the E5C gel developed in this study, offer advantages in terms of stimuliresponsive properties, biocompatibility, and modularity. By combining E5C with Atsttrin, the gel can protect against the onset and progression of post-traumatic osteoarthritis. The study provides evidence of the potential therapeutic application of the E5C gel.