Bu-Kyu Lee

Bone regeneration using a microstereolithography-produced customized poly (propylene fumarate)/diethyl fumarate photopolymer 3D scaffold incorporating BMP-2 loaded PLGA microspheres

Bony defects have been three-dimensionally (3D) created in many clinical circumstances; however, many defects cannot be reconstructed because most of the current bony substitutes cannot provide the necessary exact 3D structure. Therefore, to overcome this limitation, a 3D scaffold with embedded growth factor-delivering microspheres was developed by solid free-form fabrication (SFF) technology using computer-aided design/manufacturing (CAD/CAM). In this study, BMP-2-loaded poly(DL-lactic-co-glycolic acid) (PLGA) microspheres were incorporated into a 3D scaffold that was fabricated using a microstereolithography (MSTL) system with a suspension of microspheres and a poly(propylene fumarate) (PPF)/diethyl fumarate (DEF) photopolymer. By measuring release profiles in vitro, we verified that the fabricated microsphere-containing 3D scaffold could gradually release growth factor. The effects of BMP-2 were also assessed in vitro by observing cell differentiation using MC3T3-E1 pre-osteoblasts. Finally, we confirmed that SFF scaffolds created by MSTL were superior to traditional scaffolds produced using a particulate leaching/gas foaming method. In addition, based on in vivo tests, the scaffolds that released BMP-2 promoted bone formation. Based on these results, we concluded that our 3D scaffold might be a useful tool for enhancing reconstruction quality in many complex bony defects that should be reconstructed using a customized 3D scaffold.

In Vitro Osteogenic Differentiation of Human Mesenchymal Stem Cells and In Vivo Bone Formation in Composite Nanofiber Meshes

Tissue engineering has become an alternative method to traditional surgical treatments for the repair of bone defects, and an appropriate scaffold supporting bone formation is a key element in this approach. In the present study, nanofibrous organic and inorganic composite scaffolds containing nano-sized demineralized bone powders (DBPs) with biodegradable poly(L-lactide) (PLA) were developed using an electrospinning process for engineering bone. To assess their biocompatibility, in vitro osteogenic differentiation of human mandible-derived mesenchymal stem cells (hMSCs) cultured on PLA or PLA/DBP composite nanofiber scaffolds were examined. The mineralization of hMSCs cultured with osteogenic supplements on the PLA/DBP nanofiber scaffolds was remarkably greater than on the PLA nanofiber scaffold during the first 14 days of culture but reached the same level after 21 days. The in vivo osteoconductive effect of PLA/DBP nanofibrous scaffolds was further investigated using rats with critical-sized skull defects. Micro-computerized tomography revealed that a greater amount of newly formed bone extended across the defect area in PLA/DBP scaffolds than in the nonimplant and PLA scaffolds 12 weeks after implantation and that the defect size was almost 90% smaller. Therefore, PLA/DBP composite nanofiber scaffolds may serve as a favorable matrix for the regeneration of bone tissue.

The effect of in vitro formation of acetylcholine receptor (AChR) clusters in engineered muscle fibers on subsequent innervation of constructs in vivo

Timely innervation of muscle tissue is critical in the recovery of function, and this time-sensitive process relies heavily on the host tissue microenvironment after implantation. However, restoration of muscle tissue mass and function has been a challenge. We investigated whether pre-forming acetylcholine receptor (AChR) clusters on engineered muscle fibers using an AChR cluster-inducing factor (agrin) prior to implantation would facilitate established contacts between implanted muscle tissues and nerves and result in rapid innervation of engineered muscle in vivo. We showed that agrin treatment significantly increased the formation of AChR clusters on culture differentiated myotubes (C2C12), enhanced contacts with nerves in vitro and in vivo, and increased angiogenesis. Pre-fabrication of AChR clusters on engineered skeletal muscle using a released neurotrophic factor can accelerate innervations following implantation in vivo. This technique has considerable potential for enhancing muscle tissue function.

One-stage operation of large oroantral fistula closure, sinus lifting, and autogenous bone grafting for dental implant installation

Bone grafts to the maxillary sinus are often required after closure of an oroantral fistula (OAF) to allow for subsequent implant installation. This report describes a single procedure that closes a large OAF using bone grafting to the involved sinus. This technique involves sinus mucosal lifting via elevating the sinus membrane, which is recovered as a continuous layer by combining the residual sinus membranes with a rotated part of oral mucosa around the OAF. Autogenous bone from the ilium was grafted into the prepared sinus space, and the oral side of the graft was covered by a rotated palatal flap. This technique was used to treat 3 patients who had large OAFs in the atrophied posterior maxillary region owing to previous multiple implant failures after sinus lifting. The treatment was successful in all cases. This technique appears to be suitable for large OAFs where implants are subsequently desired.

Auricular Reconstruction Using Tissue-engineered Alloplastic Implants for Improved Clinical Outcomes

Background: Alloplastic implants have been used clinically to treat congenital abnormalities and traumatic injuries. However, these implants are often associated with complications, including inflammation, infection, erosion, and dislodgment. To minimize these complications, the authors have developed a system in which tissue-engineered cartilage serves as a shell that entirely covers the implant. This system is designed to improve the structural and functional stability between the implant and recipient tissue. Methods: Chondrocytes isolated from rabbit ear cartilage were expanded in vitro. The cells were mixed with fibrin hydrogel for spray-coating a human ear–shaped implant. The surface of the implant was modified using an oxidizing solution to provide hydrophilic characteristic; thus, the cell-fibrin suspension readily adhered onto the surface of the implants. The engineered cartilage–covered implants were implanted into the dorsal subcutaneous space of athymic mice. Histologic and gross examinations of the implants were performed at 2, 4, 8, and 12 weeks after implantation. Results: None of the engineered cartilage–covered implants showed evidence of skin necrosis, implant exposure, or extrusion (n = 10). However, the control implants developed extensive necrosis following implantation (n = 10). In the experimental group, histologic evaluations showed the formation of neocartilage covering the implants. The presence of sulfated glycosaminoglycans was evident in the engineered cartilage tissue. Conclusions: These results demonstrate that engineered cartilage tissues can be used as a biological cover for an alloplastic implant. This system may improve the structural and functional interactions between the implant and the recipient’s tissues and thus enhance the outcome of total auricular reconstruction.

Efficacy of mechanically modified electrospun poly(l-lactide-co-ε-caprolactone)/gelatin membrane on full-thickness wound healing in rats

Bioengineered skin substitute offers new opportunities for treating various skin ailments. To compensate the structural integrity problems of scaffolds prepared from natural components, we mechanically developed highly modified electrospun nanofibrous membranes, incorporating poly(l-lactide-co-ε-caprolactone) (PLCL) into gelatin [poly(l-lactide-co-ε-caprolactone)/ gelatin membrane, (P/G (3/7)]. Subsequent to our previous in vitro study, our goal was to evaluate the in vivo performance of PLCL, gelatin, and P/G (3/7) membranes, and investigate the feasibility of the newly developed P/G (3/7) membrane for wound healing. Histological analysis using the mathematical model of wound healing and contraction, revealed the association between stiffness of skin substitute with cytokeratin production and wound contraction rate, and the defect site covered with the stiffer membrane showed lower cytokeratin production, and inversely, higher wound contraction rate. Overall, the P/G (3/7) membrane induced a satisfactory wound healing outcome. However, lower cytokeratin production rate with the mechanically modified P/G membrane involves the importance of the conditional blending of PLCL. Conversely, the condition of PLCL showed some incompatibility and hindrance of skin regeneration, consistent with previous in vitro results. With proper mechanical strength and cell viability, the P/G (3/7) membrane could successfully be used as a suitable skin substitute scaffold.

Effectiveness of Autogenous Tooth Bone Graft Combined with Growth Factor

Purpose: Autogenous tooth bone graft is proven to be efficient. We evaluated the bone healing effect and clinical capabilities of autogenous tooth bone materials as a scaffold when growth factor is used together with this material. Materials and Methods: Subjects were those who needed implant placement and bone graft because of missing tooth or alveolar bone defect and who kept their autogenous tooth or needed extraction of other tooth. Group I included autogenous tooth bone graft with growth factor, whereas Group II had only autogenous tooth bone graft. We investigated the bone healing state through computed tomography taken just before surgery and 3 to 4 months after surgery to evaluate the effectiveness of bone graft. Group I had 9 patients, whereas Group II had 5 patients. We compared the pre- and post-operative increase of the Hounsfield unit and bone height by analyzing the computed tomography images. Result: Sinus bone grafts numbered 8 cases, and vertical ridge augmentation was performed together with 3 cases of these. Vertical ridge augmentation was performed in 2 cases, and horizontal ridge augmentation in 1 case alone. Socket graft was done in 3 cases. The post-operative mean value of the Hounsfield unit was 960 in Group I and 836.7 in Group II, but the increase was almost similar, i.e., 636.9 in Group I and 634.7 in Group II on the average. Increase of bone height was 7.6 mm in Group I and 11.1 mm in Group II on the average. This difference was attributable to the fact that most of the cases were sinus bone graft in Group II. Conclusion: In this study, we suggest the possibility of autogenous tooth bone graft materials as a scaffold besides their bone healing ability.

Hydroxyapatite-coated implant: Clinical prognosis assessment via a retrospective follow-up study for the average of 3 years

PURPOSE This research evaluated clinical outcomes of two types of hydroxyapatite (HA)-coated implants: OT (Osstem TS III-HA, Osstem implant Co., Busan, Korea) and ZM (Zimmer TSV-HA, Zimmer dental, Carlsbad, USA). MATERIALS AND METHODS The research was conducted on 303 implants (89 of OT, 214 of ZM), which were placed from January 16, 2010 to December 20, 2012. The prognosis was evaluated in terms of success rates, survival rates, annual marginal bone loss, and implant stability quotients (ISQ). The samples were classified into immediate, early, conventional, and delayed groups according to the loading time. RESULTS Overall, there were no significant differences between OT and ZM in success rates, survival rates, and annual marginal bone loss, except for the result of secondary stability. OT showed 77.83 ± 8.23 ISQ, which was marginally higher than 76.09 ± 6.90 ISQ of ZM (P<.05). In terms of healing periods, only immediate loading showed statistically significant differences (P<.05). Differences between OT and ZM were observed in terms of two indices, the annual marginal bone loss (0.17 ± 0.58 mm/year < 0.45 ± 0.80 mm/year) and secondary stability (84.36 ± 3.80 ISQ > 82.48 ± 3.69 ISQ) (P<.05). OT and ZM did not have any statistically significant differences in early, conventional, and delayed loading (P>.05). CONCLUSION OT (97.75%) and ZM (98.50%) showed relatively good outcomes in terms of survival rates. In general, OT and ZM did not show statistically significant differences in most indices (P>.05), although OT performed marginally better than ZM in the immediate loading and 1-stage surgery (P<.05).

P.063 Oral bisphosphonate related osteonecrosis of the jaws: a case report

Bisphosphonates are the most widely prescribed medications for the treatment of osteoporosis. However, bisphosphonate- related osteonecrosis of the jaw (BRONJ) is recently recog-nized as a serious complication among patients receiving bisphosphonate therapy. Most reports relate to BRONJ result from intravenous bisphosphonate or dental procedure. We report a case of mandible osteonecrosis related with oral bisphosphonate medication. A-63-year old woman suffered from toothache, cheek swelling and heating sense visited our dental clinic. She had taken oral alendronate and antihy-pertensive agents for 4 years because of osteoporosis and hypertension. Dental physical examination, radiologic study and pathologic study showed the severe inflammation and osteonecrosis of the mandible. Therefore we diagnosed the patient as having BRONJ and she stopped to take bispho-sphonate and received surgical treatment with bone curet-tage. After surgical treatment and stopping bisphosphonate, her symptoms were improved. (J Korean Acad Rehab Med 2010; 34: 599-602)Key Words: Osteoporosis, Bisphosphonate, Osteonecrosis서론