Injectable Progranulin-derivative Atsttrin loaded Protein Engineered Gels for Post Traumatic Osteoarthritis

Abstract

Protein-based biomaterials offer several advantages over synthetic materials, owing to their unique stimuli-responsive properties, biocompatibility and modular nature. We have successfully developed protein block polymers that consist of elastin like polypeptide (E) and the coiled-coil domain of cartilage oligomeric matrix protein (C). Here, we demonstrate that E5C, a construct consisting of five repeats of E and a single domain of 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 (PGRN), 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 hydrogels 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 PGRN-derivative Atsttrin, for prevention of OA onset and progression.

One-step stromal vascular fraction therapy in osteoarthritis with tropoelastin-enhanced autologous stromal vascular fraction gel

“…For example, a lyotropic liquid crystal (LLC) precursor-based gel, co-loaded with HA and celecoxib, which provides sustained OA treatment through antiinflammatory action and cartilage protection while maintaining biocompatibility and stress absorption (Mei et al, 2021). Besides, Priya Katyal et al developed a protein-based E5C gel that forms a network at physiological temperatures for sustained delivery of the chondroprotective agent Atsttrin, demonstrating both preventive and therapeutic effects against post-traumatic osteoarthritis in a rabbit model (Katyal et al, 2022). In addition, in a study comparing ibuprofen gel and cream phonophoresis for knee OA, gel phonophoresis demonstrated significantly greater improvements in pain and functionality as measured by VAS and WOMAC scores (Coskun Benlidayi et al, 2018).…”