Tissue Engineered Bone Grafts: Biological Requirements, Tissue Culture and Clinical Relevance

Abstract

The tremendous need for bone tissue in numerous clinical situations and the limited availability of suitable bone grafts are driving the development of tissue engineering approaches to bone repair. In order to engineer viable bone grafts, one needs to understand the mechanisms of native bone development and fracture healing, as these processes should ideally guide the selection of optimal conditions for tissue culture and implantation. Engineered bone grafts have been shown to have capacity for osteogenesis, osteoconduction, osteoinduction and osteointegration - functional connection between the host bone and the graft. Cells from various anatomical sources in conjunction with scaffolds and osteogenic factors have been shown to form bone tissue in vitro. The use of bioreactor systems to culture cells on scaffolds before implantation further improved the quality of the resulting bone grafts. Animal studies confirmed the capability of engineered grafts to form bone and integrate with the host tissues. However, the vascularization of bone remains one of the hurdles that need to be overcome if clinically sized, fully viable bone grafts are to be engineered and implanted. We discuss here the biological guidelines for tissue engineering of bone, the bioreactor cultivation of human mesenchymal stem cells on three-dimensional scaffolds, and the need for vascularization and functional integration of bone grafts following implantation.

Enhanced osteoblastogenesis in three-dimensional collagen gels

“…Autologous bone grafts are being used for the repair of large bone defects that occur as a consequence of fracture, tumor, infection and congenital deformity, but harvest of bone for grafting is often associated with donor site morbidity, and only a limited quantity of bone can be used. 3,17 Tissue engineering is considered a promising alternative approach for the repair of bone defects, aiming to restore both the structural integrity and the normal remodeling activity of bone. The development of effective scaffolds is crucial for the successful engineering of new bone tissue.…”

“…The scaffolds have to provide an osteoinductive environment for cells to migrate, proliferate, differentiate and promote new bone formation, as well as provide mechanical support during the bone regeneration. 17 Tissue engineering for restoration of bone is also considered for maxillofacial use for the regeneration of alveolar bone after trauma, tumor resection and periodontal infection. 18 A scaffold made of a combination of an absorbable collagen sponge carrier and recombinant human bone morphogenetic protein-2 (INFUSE Bone Graft), which has been shown to induce bone formation, is currently Food and Drug Administration (FDA)-approved as a bone graft substitute.…”

Bone marrow mesenchymal stem cells differentiate into urothelial cells and the implications for reconstructing urinary bladder mucosa

“…Previous research has demonstrated that stem cell transplantation may provide significant therapeutic benefits for various cardiovascular, neurodegenerative and endocrine disorders, as well as other diseases (Yamada et al 2008;Tondreau et al 2008;Ianus et al 2003;Fröhlich et al 2008). To date, however, hematopoietic stem cells (HSCs) derived from adult peripheral blood, adult bone marrow, or umbilical cord blood have been used in human clinical transplantation (Chinen and Buckley 2010).…”

The role of the microenvironment on the fate of adult stem cells

“…Bioceramic-collagen scaffolds loaded with human adipose-tissue derived SCs enhanced bone regeneration and reconstruction and also served as appropriate structures in bone regenerative medicine [87]. Furthermore, the combination of biochemical and biophysical stimulatory signals in a three-dimensional setting could potentially enhance the development of mature osteoblasts [88]. A chitosan-gelatin hydrogel containing TGF-β1 was used to promote chondrogenesis, while a polylactic-co-glycolic acid (PLGA) scaffold loading BMP-2 was used to promote osteogenesis [89,90].…”