Bone tissue engineering

Bone defects resulting from congenital anomalies, trauma, metabolic diseases, infections, and tumor removal are formidable clinical challenges for orthopedics and craniofacial surgeries. Bone tissue engineering is aimed to repair bone defects that fail to spontaneously heal. In the conventional tissue-engineering paradigm, combinations of cells and bioactive molecules are seeded onto three-dimensional (3D) biomaterial scaffolds to create an implantable “osteogenic” implant. To date and despite numerous exciting advances in investigative and preclinical models, bone tissue engineering has encountered a multitude of challenges including autologous donor cell deficiencies, immunorejections of delivered cells, excessive costs, and regulatory approval barriers. These hurdles have impeded the translation of innovative bone tissue engineering strategies from the bench to the bedside. Whereas the bone tissue engineering field continues to explore frontiers in investigative and innovative approaches toward bone defect repair, several translational advances have shown great promise toward development into potential clinical therapeutics. First, there are clinical case reports of ingenious reconstructions of challenging appendicular, axial, and craniofacial defects that, despite their origin from conventional tissue-engineering concepts of delivering cells and/or growth factors, may circumvent otherwise stringent regulatory process of cell transplantation therapies, but rather as the point-of-care treatments. However, caution must be exercised to distinguish between cell therapies that have been proven to be efficacious and safe following randomized clinical trials and those that are offered without clinical trials. Second, new or known molecules that demonstrate efficacy in repairing nonhealing bone defects are being developed with the general concept to augment endogenous bone regeneration. Relative to several other musculoskeletal tissues such as cartilage, intervertebral discs, and ligaments and tendons, bone has relatively robust endogenous capacity for repair. Delivery of new or existing osteogenic molecules that augment bone’s intrinsic capacity for self-repair has been termed cell homing, by recruiting endogenous stem/progenitor cells, that may serve as an alternative or adjunctive to cell transplantation. Third, innovative biomaterials and 3D printing offer unprecedented opportunities for bone tissue engineering and are being developed with translational goals to evolve into clinically viable therapeutics. Finally, we highlight clinical successes and opportunities for regenerating appendicular and craniofacial bone defects. In summary, bone tissue engineering continues to offer the only hope for repairing some of the bone defects that fail to heal.