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영어

Many clinical conditions in neurosurgery, orthopedics, and dental surgery require bone regeneration. The indications include bone fracture, trauma, spinal fusion, and dental implantation. Therapies for bone regeneration are various. Some of them are being used clinically and some are currently under preclinical or clinical studies. The therapies include bone grafts, bone morphogenetic protein-2 (BMP-2) protein delivery, stem cell transplantation, and gene delivery. Calcium phosphatebased ceramics, such as hydroxyapatite (HA) and tricalcium phosphate, have been used as bone substitutes, but these materials have poor mechanical performance. Recently, increasing interest has focused on using polymer/ceramic composite materials as bone substitutes to improve mechanical properties and control the biodegradation rate easily [1]. Polymer/ceramic composites have a non-uniform and limited exposure of the ceramics on the scaffolding surface. This is the result of the polymer solution enveloping the ceramic particles during the fabrication process. This problem can be overcome by two methods. One is fabricating polymer/ceramic composites using the gas-foaming method [1]. The other is exposing nano HA particles on the polymer/HA scaffolds acting as nucleation sites for apatite deposition and accelerating the apatite growth rate in a biomimetic coating approach using a simulated body fluid [2]. BMP-2 is one of the most potent growth factors for the induction of bone formation in vivo. The bone formation efficacy of BMP-2 depends on the protein delivery system, because BMPs administered in solution may lose their bioactivity over a short time and do not always exhibit the required efficacy in bone regeneration in vivo. We have developed BMP-2 delivery systems that allow for sustained and localized release of BMP-2 protein by conjugating heparin, a polysaccharide macromolecule that binds directly with BMP-2 and helps to retain BMP-2 activity, to polymer scaffolds [3], gels, or nanoparticles [4]. Stem cell
transplantation can also induce bone regeneration. Generally, bone formation by stem cell transplantation requires osteogenic differentiation of the cells prior to transplantation. However, the in vitro osteogenic differentiation requires additional culture periods of 3-4 weeks, during which patients should wait. Recently, we have developed a technology in which stem cells that are not differentiated osteogenically in vitro prior to transplantation extensively regenerate bone in vivo when exogenous BMP-2 is delivered to the transplantation site [5,6]. This method does not require an additional culture period for in vitro osteogenic differentiation and would be valuable for bone regeneration.