Summary: | 博士 === 國立陽明大學 === 醫學工程研究所 === 97 === For bone defects of different causes, reconstruction with bone graft or even vascularized bone flaps has become useful clinical modalities. Vascularized bone grafts have their own intrinsic blood supply and can therefore tolerate infection and mechanical loading better than conventional bone grafts and obtain a more rapid union. Recent advances in tissue-engineering techniques have enabled new procedures for bone regeneration that have the potential to evolve the present clinical strategies.
Collagen and (hydroxyl)apatite, the two major components of bone tissue, have been used as the bone substitute materials in orthopedic, oral-maxillo-facial and plastic surgery. In our previous studies, microspheres composed of hydroxyapatite and collagen were developed as the carrier of osteoblasts and growth factors (BMP) to assist bone healing. In this study, more in-depth application of this hydroxyapatite/collagen gel beads system for bone tissue engineering was explored.
From chapter two to four, we reported our studies on the fabrication of large segment tissue engineered bone graft (3 cm) with a predetermined shaped chamber. In chapter three, an animal model of in vivo tissue engineering of a protrusive bone was designed. We used particulate autogenous bone graft mimics that simulated potential clinical needs to create a 3D osseous tissue abundant in bone matrix and osteocytes enclosed in lacunae. Extensive fibrovascular networks were noted interstitially between these biomaterial beads in all parts of chamber. In a study reported in chapter four, we further combined guided bone regeneration technique and intermittent injection of the autologous platelet-rich-plasma into the collagen/ hydroxyapatite gel beads matrices. The specific 3D osseous tissues with fibrovascular network structure from pre-exist bony margin were also successfully created. In this study, the experimental group (group C) had significantly better engineered bone tissue (average calcified density 0.95, average calcified area 61.83%) generated as compared with other groups (p< 0.001).
In chapter five, we reported the results of combining the vascular bundle with large predetermined shape chamber to fabricate a vascularized tissue engineered bone graft. The construct of mesenchymal stem cells/hydroxyapatite/collagen gel bead composites were used. In this study, established extensive patent vascular network within the engineered bone segment was demonstrated. The matrixes had begun to degrade and surrounding osteoprogenitors and osteoblasts invaded the matrix forming new osteoids simultaneously. In our study, continually calcification in the chamber was noted and the newly formed bone tissue was found 6 months after implantation. The results of this study showed that successful in vivo engineering of vascularized tissue-engineered bone grafts is possible.
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