Relaxin-2 as a Novel Protein Therapeutic for the Treatment of Arthrofibrosis: Treatment options for arthrofibrosis are limited. Specifically, treatment for shoulder arthrofibrosis requires months to years of physical therapy or even surgical procedures. Relaxin is a hormone that is primarily released during pregnancy, which helps expand the pelvis and increases the elasticity of ligaments. Thus, hRLX-2 effects are being studied in post-iatrogenic joint contractures in wild-type rats and in joint contractures induced by rats suffering from Duchenne Muscular Dystrophy.
· Kirsch JR, Williamson AK, Yeritsyan D, Blessing WA, Momenzadeh K, Leach TR, Williamson PM, Korunes-Miller JT, DeAngelis JP, Zurakowski D, Nazarian RM, Rodriguez EK, Nazarian A, Grinstaff MW. Minimally invasive, sustained-release relaxin-2 microparticles reverse arthrofibrosis. Sci Transl Med. 2022 Oct 12;14(666):eabo3357. doi: 10.1126/scitranslmed.abo3357. Epub 2022 Oct 12. PMID: 36223449.
· Blessing WA, Okajima SM, Cubria MB, Villa-Camacho JC, Perez-Viloria M, Williamson PM, Sabogal AN, Suarez S, Ang LH, White S, Flynn E, Rodriguez EK, Grinstaff MW, Nazarian A. Intraarticular injection of relaxin-2 alleviates shoulder arthrofibrosis. Proc Natl Acad Sci U S A. 2019 Jun 18;116(25):12183-12192. doi: 10.1073/pnas.1900355116. Epub 2019 Jun 3. PMID: 31160441; PMCID: PMC6589647.
Salt Inducible Kinase Inhibitors as a Potential Novel Therapeutic for Fracture Repair: Greater than 6.8 million fractures are reported annually in the United States, accounting for 20% of all musculoskeletal injuries. Approximately 10% of fractures will experience delayed- or non-union. Parathyroid Hormone (PTH) analogues are anabolic treatments for osteoporosis, which have shown efficacy in stimulating fracture repair in animal models and in patients with chronic nonunion. A key step in PTH intracellular action is its ability to inhibit the activity of salt inducible kinases (SIKs). Development of potent and selective small-molecule SIK inhibitors to unmet the clinical need for osteoinductive agents to enhance fracture repair is critical. As an innovative alternative to the limited options available today, the proposed bone targeting through Sik2/3 Inhibitors retains efficacy in callus formation and represents a paradigm shift in fracture repair management.
Evaluation of the Efficacy of PR1P on Fracture Repair: Several growth factors are expressed in distinct temporal and spatial patterns during fracture repair. Of these, Vascular Endothelial Growth Factor (VEGF), is of particular interest, because of its ability to induce neovascularization (angiogenesis). Recently developed 12-amino acid peptide (PR1P), whose sequence is derived from an extracellular VEGF-binding domain of the pro-angiogenic glycoprotein prominin-1, has demonstrated angiogenic effects in multiple tissues. PR1P acts to stabilize VEGF and help promote the angiogenic effects of VEGF. PR1P’s effect on fracture healing is currently being studied in an animal fracture model.
Evaluate the effect of cannabinoids on bone healing following various animal models: The opioid epidemic in the United States with its enormous health and economic burden necessitates the investigation of novel non-opiate analgesia. The use of cannabinoids has increased in the general population throughout the years. Medical marijuana is an option for a non-opioid analgesic that is under investigation for potential uses in fields such as oncology and chronic pain, but it is yet to be studied in the surgical setting. Specifically, its effects on bone healing are not fully understood, significantly affecting its potential analgesic efficacy for post orthopaedic surgical care. Thus, we are studying the bone healing effects of these substances in animal models that include fracture healing and spinal fusion.
Functionalized Silk Implants: Degradable orthopedic repair devices may have clinically significant benefits over traditional permanent metal devices, by addressing current limitations in bone remodeling, degradation kinetics, and bone integration. New materials and approaches to orthopaedic hardware are required to shift the focus from passive mechanical support to a biologically-oriented integrative approach. We propose a biodegradable silk-based system impregnated with an antibiotic agent that modulates inflammatory response and prevents peri-implant infections.
