Abstract
Due to the limited supply of and numerous potential complications associated with current bone grafting materials, a tremendous clinical need exists for alternative biologically active implant materials capable of promoting bone regeneration in orthopaedic applications. Recent advances in tissue engineering technology have enabled the coating of biologically inactive materials, such as titanium fiber meshes, with a biologically active bone-like extracellular matrix produced by mesenchymal stem cells during in vitro culture. The resulting constructs can then be implanted as acellular scaffolds or as transplantation vehicles for mesenchymal stem cell populations to guide bone tissue regeneration in vivo. Such a novel tissue engineering strategy marks a paradigmatic shift in drug delivery approaches from delivering bioactive factors from a scaffold to generating constructs that contain biological signaling moieties produced by cells under engineered conditions in vitro. This chapter provides a brief introduction to general bone tissue engineering strategies and an overview of the seminal work from our laboratory in the application of mesenchymal stem cells in the in vitro generation of biologically active bone-like extracellular matrix constructs for bone tissue engineering.
Highlights
A commonly encountered challenge for reconstructive surgeons is the treatment of large bony defects resulting from traumatic injury, tumor resection, degenerative diseases, and congenital deformities
This study demonstrates that preformed bone-like extracellular matrix enhances the osteogenic differentiation of freshly seeded mesenchymal stem cells in vitro
It was found that the denatured titanium/extracellular matrix constructs resulted in significantly lower calcium content when compared to the untreated titanium/extracellular matrix constructs following 4 days of culture. These results demonstrate that fluid shear stresses act synergistically with the inherently osteogenic bone-like extracellular matrix generated during an initial flow perfusion culture period to enhance the osteogenic differentiation of mesenchymal stem cells seeded onto the extracellular matrix for a second culture period
Summary
A commonly encountered challenge for reconstructive surgeons is the treatment of large bony defects resulting from traumatic injury, tumor resection, degenerative diseases, and congenital deformities. In 2005, Nationwide Inpatient Statistics show that over 1,000,000 surgical procedures addressing the partial excision of bone, bone grafting, spinal fusion, and inpatient fracture repair were performed with total charges from these procedures exceeding $40 billion (2005), and beyond financial considerations, multiple studies have examined the psychosocial impact of orthopedic trauma and surgery (Crichlow et al, 2006; Starr et al, 2004). The cost of surgical treatment and subsequent impact on patient quality of life illustrate well the need to better address the functional and social impact of such defects
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