As the third therapy following reconstructive surgery and organ transplantation, the therapy of regenerative medicine has been currently expected. The objective of regenerative medical therapy is to induce regeneration and repairing of defective and injured tissues based on the natural-healing potential of patients themselves. For successful tissue regeneration, it is undoubtedly indispensable to create a local environment that enables cells to efficiently proliferate and differentiate, resulting in the natural induction of tissue regeneration. Tissue engineering is a biomedical technology or methodology to build up this regeneration environment. For example, the technology of drug delivery system (DDS) enhances the biological functions of growth factors and the related genes for promoted tissue regeneration. This paper overviews the recent status of tissue regeneration based on the technology of growth factor release to emphasize significance of DDS technology in regenerative medical therapy.

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Objective; The present investigation was designed to evaluate the regenerating effects of chip bone grafts harvested from implant drilling and biomaterials with or without combined application of guided bone regeneration (GBR) for the augmentation of peri-implant bone defects. Materials and methods; Four mongrel dogs were used. After the mandibular premolars were extracted for 12 weeks, surgical implantation of 4 titanium implants was performed on each side of the mandible. Chip bone was collected during the drilling procedure. Three-wall bone defects, about 2 mm high, 2 mm wide, and 3 mm long, were created at the buccal side of each implant. The osteotomy sites were separately filled with autogenous chip bone, Bio-oss mineral bone or mixture of both except one defect was left empty. The operation areas of the left mandibula were covered with titanium membranes. The right mandibles without membrane were used as controls. The dogs were sacrificed at either 9 or 16 weeks after the second operation. After the specimens containing experimental implants were resected, the resorption amount of the bone graft was measured. Then the specimens were processed for ground sectioning. The sections were stained with methylene blue and alkalescence fuchsin. Histological examination was performed and photographs were taken under photomicroscope. Results; The mean vertical distances of each bone defects were 2.64±0.17 mm in the D1 (control) group, 1.81±0.21 mm in D2 (autograft) group, 1.72±0.34 mm in D3 (Bio-oss) group, 1.51±0.22 mm in D4 (mixture) group. Statistical analysis demonstrated that there was significant difference between the results of D1 and the results of other three groups (p<0.01). No statistical differences were revealed between autograft group and Bio-oss group, as well as Bio-oss group and mixture group. It is confirmed there was significant difference between autograft group and mixture group (p<0.05). Histological observations revealed both quantity and quality of regenerated bone in the mixture grafted specimens were superior to that of single Bio-oss grafted or single autologous bone grafted specimens. Whether the membranes were utilized or not, vertical distances of the defects were larger at 16 weeks than those at 9 weeks in all the groups. Bone grafts with titanium membranes were subjected to greater resorption than those without membrane coverings at either 9 weeks or 16 weeks. Statistical analysis indicated there were significant differences in the results between the two groups (p<0.01). Conclusions: This investigation demonstrated the utilization of bone chip collected during implant drilling in combination with biomaterial was a feasible methods for repairing the limited bone defect around the implant. Using the mixture of autogenous bone and Bio-oss mineral as grafting material may significantly promote the bone regenerating effects. The functions of titanium membrane need to be further investigated.

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Rheumatoid disease (RA) is one of the complex diseases that showed multiple progression stages. At first inflammatory response is occurred by self antibodies, and then the proliferation of synoviocytes is abnormally promoted. These synoviocytes invade into articular structures and finally articular cartilage is destroyed. In order to analyze growth-promoting factors in synovial cells from articular tissues of RA, we performed DNA microarray analysis and compared the expression patterns of their mRNA to that of synoviocytes from osteoarthritis (OA). The results showed that the expression of many genes was up-regulated in RA synoviocytes comparing with OA synoviocytes. Among these genes, RT-PCR analysis revealed that Wnt-1-induced secreted protein 2 (WISP-2, CCN5) and protein 3 (WISP-3, CCN6) which are belong to the novel gene family, CCN, were highly up-regulated in RA synoviocytes. In addition, one truncated isoform of WISP-3 which may be related to the ongoing of some type of RA, was detected in RA synoviocytes. Furthermore, immunohistochemical analysis showed that the products of both CCN genes were highly distributed in active synoviocytes of articular tissues of RA. These results indicate that both CCN genes and their products play some roles in the progression of RA.

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To clarify what type of cells lead vascular invasion of epiphyseal growth plate in developing long bones, we conducted immunohistochemical and electron microscopic studies on the op/op mouse tibia which has an inheriting deficiency of macrophages and osteoclasts. Despite an absence of both TRAP-positive osteoclasts and F4/80-positive macrophages, resorption of epiphyseal cartilage followed by vascular invasion was evident in op/op mouse tibiae. Electron microscopic observation revealed that cells subjacent to the lowermost hypertrophic chondrocyte lacunae were almost exclusively vascular endothelial cells. Immunohistochemically, both cellular elements and extracellular matrix at the vascular invasion front of op/op mouse epiphysis were strongly positive for MMP-9. In situ hybridization revealed a distinct localization of mRNA for MMP-9 in cells located at the same region. From these findings, we hypothesize that vascular endothelial cells themselves are primarily responsible for resorbing the transverse septa of hypertrophic chondrocytes lacunae, and neither osteoclasts nor macrophages involve in this process.

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A new calcium silicate/vermiculite composite for building material has been prepared from unfired vermiculite, calcium hydroxide, silica and pulp by autoclaving at 187°C at a pressure of 1.08 MPa. The product exhibited the vermiculite crystals dispersed uniformly in a definite direction among the matrix of calcium silicate. The composite showed marked plastic deformation caused by interlayer sliding of vermiculite. The building material was fixed by nails and screws and also possible to cut and saw like artificial wood. The board had superior humidity control originated from chemical adsorption of water molecules at the interlayer of vermiculite, and relative humidity in an experimental house was maintained to be 50%. Formaldehyde was chemically adsorbed to the composite, and there was no release of formaldehyde at elevated temperature.

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