Factors influencing the long-term behavior of extracellular matrix-derived scaffolds for musculoskeletal soft tissue repair

Musculoskeletal connective tissues such as tendon, ligament, and cartilage possess a limited ability for self-repair. Tissue engineering seeks to use combinations of cells, bioactive molecules, and biomaterials to develop new treatment options for the repair or replacement of damaged tissues. The use of native extracellular matrix as scaffold material for tissue engineering has become increasingly attractive because such tissues can not only provide structural support, but also regulate cell behavior. Although demineralized bone matrix has long been recognized for its osteoinductive abilities, recent studies have identified the ability of cartilage and tendon extracellular matrices to stimulate the differentiation of mesenchymal or adipose-derived adult stem cells toward chondrogenic or tenogenic lineages, respectively. This review discusses the motivation for fabricating scaffolds from musculoskeletal tissues, the in vitro and in vivo efficacy of these tissue-derived scaffolds, and various processing techniques such as decellularization or cross-linking that can mitigate immunogenic responses, moderate the degradation profile, and enhance the mechanical properties of these constructs following long-term implantation in vivo.