Development, characterization and clinical use of a biodegradable composite scaffold for bone engineering in oro-maxillo-facial surgery

Abstract

We have developed a biodegradable composite scaffold for bone tissue engineering applications with a pore size and interconnecting macroporosity similar to those of human trabecular bone. The scaffold is fabricated by a process of particle leaching and phase inversion from poly(lactideco-glycolide) (PLGA) and two calcium phosphate (CaP) phases both of which are resorbable by osteoclasts; the first a particulate within the polymer structure and the second a thin ubiquitous coating. The 3-5 μm thick osteoconductive surface CaP abrogates the putative foreign body giant cell response to the underlying polymer, while the internal CaP phase provides dimensional stability in an otherwise highly compliant structure. The scaffold may be used as a biomaterial alone, as a carrier for cells or a three-phase drug delivery device. Due to the highly interconnected macroporosity ranging from 81% to 91%, with macropores of 0.8∼1.8 mm, and an ability to wick up blood, the scaffold acts as both a clot-retention device and an osteoconductive support for host bone growth. As a cell delivery vehicle, the scaffold can be first seeded with human mesenchymal cells which can then contribute to bone formation in orthotopic implantation sites, as we show in immune-compromised animal hosts. We have also employed this scaffold in both lithomorph and particulate forms in human patients to maintain alveolar bone height following tooth extraction, and augment alveolar bone height through standard sinus lift approaches. We provide a clinical case report of both of these applications; and we show that the scaffold served to regenerate sufficient bone tissue in the wound site to provide a sound foundation for dental implant placement. At the time of writing, such implants have been in occlusal function for periods of up to 3 years in sites regenerated through the use of the scaffold.

Biomimetic tubular nanofiber mesh and platelet rich plasma-mediated delivery of BMP-7 for large bone defect regeneration

“…Comprehensive in vitro and in vivo studies have demonstrated the positive influence of biomimetic apatite coating on the proliferative and osteoconductive properties of PLGA scaffolds (Davies et al 2010). A comprehensive review was compiled by Kretlow and Mikos (Kretlow and Mikos 2007).…”

Umbilical Cord Perivascular Cells: A Mesenchymal Cell Source for Treatment of Tendon Injuries

“…However, we have shown in different studies that HUCPVCs can contribute to bone [25], cartilage [14], and dermal tissue [26] in vivo, and thus it may be reasonable to expect that the collagen expression data in this study would have reflected some synthetic activity in vivo. Indeed, the change from ovoid to elongated morphology by 30 days could be indicative of tenocytic differentiation, although our primers for decorin, tenomodulin, and tenascin-C were unable to distinguish between the human and rat tenocyte phenotypes.…”

Application of Synthetic Biology to Regenerative Medicine

“…The green line shows publications for laser surgery, chosen as a 'control' for the general gentle rise in medical publication. This graph was obtained by performing a PubMed search using the termthe formation of a collagen pattern in the shape of a human nipple [15], the formation of functional heart valves [16], reconstruction of cartilage [17], bone [18], oesophagus [19] and bladder wall [20]. In a variation on that theme, the engineering of structures that already incorporate cells in situ has been used to produce functional heart tissue [21].…”