Stem cells, growth factors and scaffolds in craniofacial regenerative medicine

Abstract

Current reconstructive approaches to large craniofacial skeletal defects are often complicated and challenging. Critical-sized defects are unable to heal via natural regenerative processes and require surgical intervention, traditionally involving autologous bone (mainly in the form of nonvascularized grafts) or alloplasts. Autologous bone grafts remain the gold standard of care in spite of the associated risk of donor site morbidity. Tissue engineering approaches represent a promising alternative that would serve to facilitate bone regeneration even in large craniofacial skeletal defects. This strategy has been tested in a myriad of iterations by utilizing a variety of osteoconductive scaffold materials, osteoblastic stem cells, as well as osteoinductive growth factors and small molecules. One of the major challenges facing tissue engineers is creating a scaffold fulfilling the properties necessary for controlled bone regeneration. These properties include osteoconduction, osetoinduction, biocompatibility, biodegradability, vascularization, and progenitor cell retention. This review will provide an overview of how optimization of the aforementioned scaffold parameters facilitates bone regenerative capabilities as well as a discussion of common osteoconductive scaffold materials.

Keywords: Scaffolds; bone regeneration; craniofacial defects; osteogenesis; regenerative medicine; tissue engineering.

Fig. 1

Case example of a pediatric craniofacial defect. A) Depicted is a large craniofacial skeletal defect resulting from resorption of an autogenous bone graft following emergency craniectomy and delayed replacement of the bone. B) Reconstruction was accomplished through a second autograft involving full-thickness resection of large portions of the frontal and right parietal bones. The donor site was repaired using demineralized bone matrix and particulate bone graft. The use of these CT images follows the guidelines of the University of Chicago Institutional Review Board.

Fig. 2

Tissue engineering paradigm for craniofacial defect repair. Illustration depicting ideal modality for craniofacial defect repair. The strategy involves growth factor-induced osteoblastic differentiation and bone formation within an osteoconductive and biodegradable scaffold.

Fig. 3

Osteoblastic stem cell sources. The potential sources of mesenchymal stem cells (MSCs) that can be used for bone tissue engineering and regeneration. The recently described urine-derived stem cells (USCs) may represent one of the most promising and convenient sources of MSCs for tissue engineering and regenerative medicine.