Decellularized tendon-based heparinized nanocomposite scaffolds for prospective regenerative applications: Chemical,...

The development of cell-free regenerative biomaterials is among the current approaches of tissue engineering (TE). While materials targeting homogeneous continuous tissues can be produced more easily, significant difficulties are encountered in composite tissue interfaces such as the tendon-bone. The complex bioactive and chemical contents of the microenvironment in neighboring tissues make this situation even more difficult. While target tissue can be significantly mimicked with decellularized tissues, there is a need for incorporation of inorganic components into composite interfaces. The regenerative properties of biomaterials can be regulated by enriching them with growth factors, and the mechanical properties can be imparted by developing nanocomposites of right composition. In the first phase of the study, protocols were optimized to obtain bovine tendon-based scaffolds with high bioactive content from decellularized hydrogels. The results showed that DNA could be removed from tissues (<50 ng/mg ECM) using 0.1% SDS and 0.1% EDTA after freeze-thaw, and the content of sGAGs, an important component for tendon tissue repair, was preserved in the final product at >50%. In the second stage, the scaffolds were produced in composite form containing different amounts of nanohydroxyapatite (HAp). In the final stage, tendon-based nanocomposite scaffolds were activated with heparin to impart growth factor binding affinity. The physical, chemical, thermal, mechanical and in vitro biological properties of the scaffolds were studied in detail. The findings revealed that HAp increased the thermal stability and compressive strength; and heparin could be successfully integrated into scaffolds. Nanocomposite scaffolds were found to be highly hemocompatible.