Surgical mesh materials composed of extracellular matrix (ECM) can promote functional tissue remodeling by mechanisms that include stem cell maturation and differentiation and modulation of the host immune response toward a regulatory, pro-healing phenotype. There are two objectives for the present work: 1) to determine if an antibiotic coated version of a biologic scaffold (i.e., XenMatrix™ AB) that showed efficacy for promoting muscle regeneration in patients with volumetric muscle loss (VML) in a previous human cohort study could perform equally well, and 2) to develop and test an alternative antibiotic coating that has the added benefit of enhancing the strength of soft tissue repair.
From 2011 to 2015, we conducted a thirteen-patient cohort study in which ECM surgical meshes were used to treat VML. Results showed significant restoration of vascularized, innervated, and functional skeletal muscle with a marked improvement in the quality of life for all patients (ClinicalTrails.gov, identifier NCT01292876). The objective of the present proposal is to corroborate and extend the findings of the previous study by utilizing XENMATRIX™ AB, an FDA-approved ECM-based surgical mesh coated with a bioresorbable L-Tyrosine succinate polymer which serves as a carrier for the antibacterial agents Rifampin and Minocycline. The proposed study will assess structure and function in patients undergoing musculotendinous tissue unit repair and reinforcement with XENMATRIX™ AB. Herein, we will treat ten additional patients with XENMATRIX™ AB, an FDA-approved antibiotic-coated version of the same product used in the thirteen-patient cohort study.
We will simultaneously evaluate the effect of an enhanced version of XENMATRIX™ AB upon the healing response and functional outcome in established preclinical animal models of VML. The enhanced version involves a substitution of the antibiotic doxycycline for minocycline. The objective of the preclinical animal studies is to develop an off-the-shelf biologic prototype of XenMatrix™ with a Doxycycline plus Rifampin surface coating capable of treating traumatic large-volume muscle loss (VML) injuries of the extremities, decreasing the risk of infection, and maximizing the strength of new muscle tissue. Preliminary work in our laboratory and in studies by others shows a 33% increase in strength of the remodeled tissue with doxycycline. This project has been approved for Phase II funding of $11 million which would move forward with the enhanced version.