• Archives of Pharmacal Research
• /
• 제26권1호
• /
• pp.76-82
• /
• 2003

Drug releasing porous poly($\varepsilon$-caprolactone) (PCL)-chitosan matrices were fabricated for bone regenerative therapy. Porous matrices made of biodegradable polymers have been playing a crucial role as bone substitutes and as tissue-engineered scaffolds in bone regenerative therapy. The matrices provided mechanical support for the developing tissue and enhanced tissue formation by releasing active agent in controlled manner. Chitosan was employed to enhance hydrophilicity and biocompatibility of the PCL matrices. PDGF-BB was incorporated into PCL-chitosan matrices to induce enhanced bone regeneration efficacy. PCL-chitosan matrices retained a porous structure with a 100-200 $\mu$m pore diameter that was suitable for cellular migration and osteoid ingrowth. $NaHCO_3$ as a porogen was incorporated 5% ratio to polymer weight to form highly porous scaffolds. PDGF-BB was released from PCL-chitosan matrices maintaining therapeutic concentration for 4 week. High osteoblasts attachment level and proliferation was observed from PCL-chitosan matrices. Scanning electron microscopic examination indicated that cultured osteoblasts showed round form and spread pseudopods after 1 day and showed broad cytoplasmic extension after 14 days. PCL-chitosan matrices promoted bone regeneration and PDGF-BB loaded matrices obtained enhanced bone formation in rat calvarial defect. These results suggested that the PDGF-BB releasing PCL-chitosan porous matrices may be potentially used as tissue engineering scaffolds or bone substitutes with high bone regenerative efficacy.

• Journal of Periodontal and Implant Science
• /
• 제28권4호
• /
• pp.611-632
• /
• 1998

Chitosan has been known as a wound healing agent. The purpose of this study was to evaluate the biocompatibility and guided bone regenerative effect of chitosan and chitosan-cellulose membranes. The effects of chitosan and chitosan-cellulose membranes on the growth and survival of human periodontal ligament cells were examined by rapid colorimetric MTT(tetrazolium) assay, and the tissue response and resorption pattern were observed by implanting the membranes into the subcutaneous tissue of the back of rats for 6 weeks. To evaluate the guided bone regenerative potential of membranes, the amount of newly formed bone in the rat calvarial defects(8mm in diameter) was measured by histomorphometry and radiomorphometry 1,2 and 4 weeks after implantation of membranes. Chitosan and chitosan-cellulose membranes showed no adverse effect on the growth and survival of human periodontal ligament cells. When membranes were subcutaneously implanted, inflammatory reaction was observed at 1 week and which gradually subsided 2weeks after implantation. Membranes remained intact throughout the experimental period of 6 weeks. Radiomorphometric analysis of the craniotomy sites revealed that chitosan and chitosan-cellulose membrane implanted sites showed increased radiopacity over control. Statistically significant differences with control were found in chitosan-cellulose membrane implanted group at 2 and 4 weeks, and chitosan membrane implanted group at 4 weeks(P<0.05). Histomorphometric data indicated a pattern of osseous healing similar to radiomorphometric analysis. There was a statistically significant difference between control and chitosan-cellulose membrane implanted group at 4 weeks(P<0.05). These results implicate that chitosan and chitosan-cellulose membrane might be useful for guided bone regeneration.

• Journal of Periodontal and Implant Science
• /
• 제30권4호
• /
• pp.885-894
• /
• 2000

Deer antler has been widely prescribed in Chinese and Korean pharmacology. Although there have been several reports concerning the effects of deer antler, such as anti-aging action, anti-inflammatory activity, antifungal action and regulatory activity of the level of glucose, the effect on bone has not determined yet. The purpose of this study was to examine the effect of deer antler on osteoblast differentiation. Hexane extract(CN-H) and chloroform extract(CN-C) were acquired from deer antler(Cervus nippon) and MC3T3-E1 pre-osteoblasts were cultured in the presence or absence of each extract. Osteoblast differentiation was estimated with the formation of mineralized nodules and the mRNA expression of alkaline phosphatase(ALP), osteocalcin(OC) and bone sialoprotein(BSP) which are markers of osteoblast differentiation. Non-treated group did not show mineralized nodule. CN-C or CN-H-treated group showed minerlaized nodules in 16 days. In northern blot analysis, CN-C or CN-H-treated group showed the elevated expression of ALP, BSP and OC in 16 days. These results suggest the possibility to develop deer antler as a bone regenerative agent in periodontal therapy by showing the stimulating activity of deer antler on differentiation of osteoblast.

• BMB Reports
• /
• 제52권6호
• /
• pp.409-414
• /
• 2019

Natural compounds isolated from medicinal herbs and plants have immense significance in maintaining bone health. Hydrolysable tannins have been shown to possess a variety of medicinal properties including antiviral, anticancer, and anti-osteoclastogenic activities. As a part of a study on the discovery of alternative agent against skeletal diseases, we isolated a hydrolysable tannin, 2-O-digalloyl-1,3,4,6-tetra-O-galloyl-${\beta}$-D-glucose (DTOGG), from Galla Rhois and examined the effect on osteoclast formation and function. We found that DTOGG significantly inhibited receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation by downregulating the expression of the key regulator in osteoclastogenesis as well as osteoclast-related genes. Analysis of RANKL/RANK signaling revealed that DTOGG impaired activation of $I{\kappa}B{\alpha}$ and p65 in the nuclear factor kappa-lightchain-enhancer of activated B cells (NF-${\kappa}B$) signaling pathway. Furthermore, DTOGG reduced bone resorbing activity of osteoclasts, compared to the vehicle-treated control. These results suggest that DTOGG could be a useful natural compound to manage osteoclast-mediated skeletal diseases.

• Journal of Periodontal and Implant Science
• /
• 제38권2호
• /
• pp.125-134
• /
• 2008

Purpose: Bone morphogenetic protein (BMP) is a potent differentiating agent for cells of the osteoblastic lineage. It has been used in the oral cavity under a variety of indications and with different carriers. However, the optimal carrier for each indication is not known. This study evaluated the bone regenerative effect of rhBMP-2 delivered with different carrier systems. Materials and Methods: 8 mm critical-sized rat calvarial defects were used in 60 male Sprague-Dawley rats. The animals were divided into 6 groups containing 10 animals each. Two groups were controls that had no treatment and absorbable collagen membrane only. 4 groups were experimentals that contained rhBMP-2 only and applied with absorbable collagen sponge($Collatape^{(R)}$), $MBCP^{(R)}$, Bio-$Oss^{(R)}$ each. The histological and histometric parameters were used to evaluate the defects after 2- or 8-week healing period. The shape and total augmented area were stable in all groups over the healing time. Results: New bone formation was significantly greater in the rhBMP-2 with carrier group than control group. rhBMP-2/ACS was the highest in bone density but gained less new bone area than rhBMP-2/$MBCP^{(R)}$ and rhBMP-2/Bio-$Oss^{(R)}$. The bone density after 8 weeks was greater than that after 2 weeks in all groups. However, rhBMP-2 alone failed to show the statistically significant difference in new bone area and bone density compared to control group. Also $MBCP^{(R)}$ and Bio-$Oss^{(R)}$ particles remained after 8 weeks healing period. Conclusion: These results suggest that rhBMP-2 with carrier system is an excellent inductive agent for bone formation and we can use it as the predictable bone tissue engieering technique. Future study will likely focus on the kinetics of BMP release and development of carriers that is ideal for it.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• 제38권
• /
• pp.16.1-16.9
• /
• 2016

Background: The association of biomaterial combined with repair factor-like platelet-rich plasma (PRP) has prospective values. Bovine-derived xenograft has been identified as an osteoconductive and biocompatible grafting material that provides osseointegration ability. PRP has become a valuable adjunctive agent to promote healing in a lot of dental and oral surgery procedures. However, there are controversies with respect to the regenerative capacity of PRP and the real benefits of its use in bone grafts. The purpose of this study was to assess the influence of PRP combined with xenograft for the repair of peri-implant bone defects. Methods: Twelve rabbits were used in this study, and the experimental surgery with implant installation was performed simultaneously. Autologous PRP was prepared before the surgical procedure. An intrabony defect (7.0 mm in diameter and 3.0 mm deep) was created in the tibia of each rabbit; then, 24 titanium dental implants (3.0 mm in diameter and 8.5 mm long) were inserted into these osteotomy sites. Thus, a standardized gap (4.0 mm) was established between the surrounding bony walls and the implant surface. The gaps were treated with either xenograft alone (control group) or xenograft combined with PRP (experimental group). After healing for 1, 2, 3, 4, 5, and 6 weeks, the rabbits were sacrificed with an overdose of KCl solution. Two rabbits were killed at each time, and the samples including dental implants and surrounding bone were collected and processed for histological analysis. Results: More newly formed bone and a better bone healing process were observed in control group. The histomorphometric analysis revealed that the mean percentage of bone-to-implant contact in the control group was significantly higher than that of the experimental group (25.23 vs. 8.16 %; P < 0.05, independent-simple t test, analysis of variance [ANOVA]). Conclusions: The results indicate that in the addition of PRP to bovine-derived xenograft in the repair of bone defects around the implant, PRP may delay peri-implant bone healing.

• Journal of Periodontal and Implant Science
• /
• 제28권4호
• /
• pp.545-559
• /
• 1998

Magnoliae cortex has been used as a drug for treatment of fractures in Chinese medicine and safflower(Carthamus tinctorius $Linn{\acute{e}}$) has been traditionally used for treatment of blood stasis. The purpose of present study was to examine the biologic effects of magnoliae cortex extract and safflower extract mixture(MSM) on human periodontal ligament cells and fetal rat calvarial osteoblasts and on healing of rat calvarial defects. The ethanolic extracts of magnoliae cortex(MCE), safflower seed(SSE), Zea May L(ZML) were prepared as positive control group. MSM mixed to the ratios of 1 : 1, 1 : 2, 1 : 5 and 1 : 10 were used as test group. The effects of each agents on the growth and survival, ALPase activity, cell proliferation and tissue regenerative effect of each extracts was evaluated by histomorphometric measuring of newly formed bone on the 8 mm defect in rat calvaria after oral administration of 2 ratio groups(1 : 5 and 1 : 10) at 3 different doses (0.1, 0.25 and 0.5g/kg per day). MSM stimulated the growth and survival rate of osteoblasts and PDL cells more than any other agents. The growth and survival rate were increased as the proportion of safflower seed extract was increased. MCE, SSE, ZML stimulated the ALPase activity of osteoblast and PDL cell in comparison to the negative control group. But all groups of MSM regardless of ratio of safflower seed extract stimulated the ALPase activity than any other agent. The ALPase activity was also increased as the proportion of safflower seed extract was increased. Although MCE, SSE, ZML stimulated the proliferation of osteoblasts. 1 : 5 and 1 : 10 ratio MSM showed significant increase in stimulation of proliferation of osteoblasts. No agent significantly increased proliferation of PDL cells. Significant new bone formation were seen where 1 : 5 ratio, 0.5g/kg group and 1 : 10 ratio, 0.25, 0.5g/kg groups were used. These results show that magnoliae cortex extract and safflower seed extract mixture can potentially increase bone regeneration ability.