Developing Porcine Bone Extracellular Matrix (ECM) Hydrogel for Tissue Regeneration

Background: Bone is a dynamic tissue with the ability to heal and repair without scaring. Nevertheless, in cases of delayed recovery or large non-healing bone defect resulting from trauma, tumor or infection bone grafting is required. The extracellular matrix (ECM) naturally provides cells with a supportive framework of structural as well as functional proteins, carbohydrates, and signaling molecules. The ECM was proved to have an important role in creating the foundation for successful bone healing as it increases the interactions among osteoprogenitor cells and growth factors. Our aim is, therefore, to harness the natural advantages of ECM to develop a well-defined, tailor-made scaffold for bone regeneration. Methods: Porcine bone ECM (pbECM) was isolated from native bone tissue and decellularized. Then, the pbECM was enzymatically solubilized to produce a thermally-induced hydrogel. The hydrogel was further assessed to investigate its distinctive properties, and its consequent ability to support cells for biomedical applications. Results: Hydrogel characterization through collagen immunostaining revealed that the collagen fibrous structure is preserved through the solubilization process. Evaluating the rheological properties of the hydrogel revealed soft gel behavior. Mesenchymal stem cells and human induced pluripotent stem cells were successfully cultivated on the hydrogel and their viability, proliferation, ECM remodeling and differentiation towards bone were determined. Conclusion: We successfully developed porcine bone tissue decellularization and solubilization process to form a hydrogel, which has the potential to recruit cells and deliver growth factors. The hydrogel supports stem cells’ culture and viability. Therefore, pbECM is a promising candidate for bone regeneration applications.