Incorporation of the Amniotic Membrane as an Immunomodulatory Design Element in Collagen Scaffolds for Tendon Repair

Tendon injuries often require surgical intervention and even then result in poor outcomes due to scar formation and repeated failure. Biomaterial implants offer the potential to address multiple underlying concerns preventing improved tendon repair. Here, we describe modifications to the composition of an anisotropic collagen-glycosaminoglycan (CG) scaffold biomaterial, incorporating amniotic membrane (AM)-derived matrix to alter the inflammatory response and establish conditions for improved regenerative repair. We explored two methods of AM matrix incorporation to address multiple concerns associated with tendon repair. Amniotic membrane-derived matrix was incorporated directly into the scaffold microstructure during fabrication to form a C/AM composite. Alternatively, decellularized amniotic matrix was wrapped around the traditional collagen-chondroitin sulfate (C/CS) scaffold to form a core-shell composite (C/CS plus AM wrap) in a manner similar to current collagen membrane wraps used in rotator cuff and Achilles tendon surgeries to improve the mechanical strength of the repair. Human mesenchymal stem cells (MSCs) cultured within these materials were evaluated for metabolic health and immunomodulatory gene expression in response to inflammatory media challenge of interleukin 1 β and tumor necrosis factor α. The scaffolds were able to maintain MSC metabolic activity in all media conditions over the course of a 7 day culture. Expression of genes encoding for pro-inflammatory cytokines were down-regulated in AM containing scaffolds, suggesting the potential to employ AM-modified CG scaffolds for tendon-repair applications.