Off-the-shelf implantable biomaterials for tissue engineering and regenerative medicine (TERM) applications can treat numerous damaged organs/tissues. Such biomaterials have been investigated for their natural and synthetic biomimetic material properties to induce tissue regeneration in situ. Engineering biomaterials based off their mechanical properties like that of tensile strengths, porosity, nanofiber widths, or moduli can aid in tissue repair. However, tuning biomechanical properties alone is not always sufficient for biomaterials to induce effective tissue regeneration of large tissue/organ defects. The inclusion of biological properties to certain biomaterials such as stem/progenitor cells, growth factors, and/or cytokines can attenuate inflammation and stimulate proper tissue regeneration. In order to develop better off-the-shelf biomaterial implants for tissue repair, both the biomechanical and biological properties of the engineered biomaterial implant need to be assessed. In this dissertation, a decellularized polycaprolactone/chitosan hollow tube grown with MSC2s (De-PCL/CS) is investigated as a novel off-the-shelf tissue engineered graft (OTS-TEG) to repair hollow tubular organs like that of the esophagus. It is demonstrated that De-PCL/CS can retain extracellular matrix (ECM) factors from anti-inflammatory MSC2s post freeze-thaw decellularization. De-PCL/CS exhibits similar esophageal compressive biomechanics and is shown in an in vivo murine omentum model to be anti- inflammatory while robustly recruiting gastrointestinal (GI) cells. This gives great insight into De-PCL/CS as an immune modulating biomaterial to attenuate inflammation while promoting tissue repair for GI applications. Severe esophageal malignancies like esophageal cancer (EC), advanced Barrett’s Esophagus (BE), and pediatric atresia require GI reconstructive surgery (i.e. gastric pull up). De-PCL/CS has the translational capability as an implantable OTS-TEG to regenerate damaged esophageal tissue avoiding a gastric pull up. This not only increases the quality of life of the patient receiving this treatment but has an immediate potential impact of over $2.2 billion saved annually on the U.S. healthcare system. Nevertheless, the unique bioengineering patent-pending methods in developing De-PCL/CS allow it to be a platform OTS-TEG for treating a plethora of damaged organs/tissues. Translationally, De-PCL/CS can have a great therapeutic impact in the TERM global market that is expected to accrue over $100 billion by the mid 2020s.
