Erratum to “Collagen Sponge Functionalized with Chimeric Anti-BMP-2 Monoclonal Antibody Mediates Repair of Critical-Size Mandibular Continuity Defects in a Nonhuman Primate Model”

Antibody-mediated osseous regeneration (AMOR) has been introduced by our research group as a tissue engineering approach to capture of endogenous growth factors through the application of specific monoclonal antibodies (mAbs) immobilized on a scaffold. Specifically, anti-Bone Morphogenetic Protein- (BMP-) 2 mAbs have been demonstrated to be efficacious in mediating bone repair in a number of bone defects. The present study sought to investigate the application of AMOR for repair of mandibular continuity defect in nonhuman primates. Critical-sized mandibular continuity defects were created in Macaca fascicularis locally implanted with absorbable collagen sponges (ACS) functionalized with chimeric anti-BMP-2 mAb or isotype control mAb. 2D and 3D analysis of cone beam computed tomography (CBCT) imaging demonstrated increased bone density and volume observed within mandibular continuity defects implanted with collagen scaffolds functionalized with anti-BMP-2 mAb, compared with isotype-matched control mAb. Both CBCT imaging and histologic examination demonstrated de novo bone formation that was in direct apposition to the margins of the resected bone. It is hypothesized that bone injury may be necessary for AMOR. This is evidenced by de novo bone formation adjacent to resected bone margins, which may be the source of endogenous BMPs captured by anti-BMP-2 mAb, in turn mediating bone repair

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It is an empirical research on the form and presentation of the SFS in Singapore. The areas covered are with regard to the explanation of the terms, the linguististic and graphical presentation of information in SFS. It is an exploratory study

Neutrophil‐mediated enhancement of angiogenesis and osteogenesis in a novel triple cell co‐culture model with endothelial cells and osteoblasts

Repair and regeneration of critical‐sized bone defects remain a major challenge in orthopaedic and craniomaxillofacial surgery. Until now, attempts to bioengineer bone tissue have been hindered by the inability to establish proper angiogenesis and osteogenesis in the tissue construct. In the present study, we established a novel triple cell co‐culture model consisting of osteoblasts, endothelial cells, and neutrophils and conducted a systematic investigation of the effects of neutrophils on angiogenesis and osteogenesis. Neutrophils significantly increased angiogenesis in the tissue construct, evidenced by the formation of microvessel‐like structures with an extensive lattice‐like, stable tubular network in the co‐culture model. Moreover, neutrophils significantly induced the expression of pro‐angiogenic markers, such as VEGF‐A, CD34, EGF, and FGF‐2 in a dose‐ and time‐dependent manner. Subsequently, PCR arrays corroborated that neutrophils upregulate the important angiogenic markers and MMPs. Moreover, neutrophils also enhanced osteogenic markers, such as ALP, OCN, OPN, and COL‐1 compared with the controls. As shown by the osteogenic gene arrays, neutrophils significantly regulated major osteogenic markers such as BMP2, BMP3, BMP4, BMP5, TGF‐β2, RUNX2, and ECM proteins. Significantly higher mineralization was observed in triple cell co‐culture compared with controls. Foregoing data indicate that the triple cell co‐culture model can be used to stimulate the growth of microvasculature within a bone bioengineering construct to improve cell viability. Neutrophil‐mediated enhancement of angiogenesis and osteogenesis could be a viable, clinically relevant tissue engineering strategy to obtain optimal bone growth in defect sites, in the field of oral and maxillofacial surgery.NMRC (Natl Medical Research Council, S’pore

Preliminary investigation on the geometric accuracy of 3D printed dental implant using a monkey maxilla incisor model

Additive manufacturing has proven to be a viable alternative to conventional manufacturing methodologies for metallic implants due to its capability to customize and fabricate novel and complex geometries. Specific to its use in dental applications, various groups have reported successful outcomes for customized root-analog dental implants in preclinical and clinical studies. However, geometrical accuracy of the fabricated samples has never been analyzed. In this article, we studied the geometric accuracy of a 3D printed titanium dental implant design against the tooth root of the monkey maxilla incisor. Monkey maxillas were scanned using cone-beam computed tomography, then segmentation of the incisor tooth roots was performed before the fabrication of titanium dental implants using a laser powder bed fusion (PBF) process. Our results showed 68.70% ± 5.63 accuracy of the 3D printed dental implant compared to the actual tooth (n = 8), where main regions of inaccuracies were found at the tooth apex. The laser PBF fabrication process of the dental implants showed a relatively high level of accuracy of 90.59% ± 4.75 accuracy (n = 8). Our eventual goal is to develop an accurate workflow methodology to support the fabrication of patient-specific 3D-printed titanium dental implants that mimic patients’ tooth anatomy and fit precisely within the socket upon tooth extraction. This is essential for promoting primary stability and osseointegration of dental implants in the longer termNational Research Foundation (NRF)Published versionThis work is funded by the National Health Innovation Centre Singapore (NHIC-I2D-1712189) and National Research Foundation, Prime Minister’s Office, Singapore under its Medium-Sized Centre funding scheme

Modular Endoprosthesis for Mandibular Reconstruction — A Thematic Research Study at the National Dental Centre Singapore

Introduction: A thematic research project was undertaken by the National Dental Centre Singapore to study the feasibility of using a novel modular endoprosthesis for reconstruction of the mandible. Successful application of this technique potentially eliminates the need for a donor site. Methods: Three sub-projects done in a monkey model are presented. In the first two sub-projects, a titanium modular endoprosthesis was inserted in surgically created defects for reconstruction of the ascending ramus and condyle; and body of the mandible respectively. In the third sub-project, a polycaprolactone scaffold with calcium phosphate (CaP) surface coating modular endoprosthesis was used for reconstruction of the body of the mandible. The animals were sacrificed at three to six months. Microcomputed tomographic and histologic analyses were done. Results: At the time of sacrifice, signs of infection were present in a few animals treated either with the titanium or the polycaprolactone endoprosthesis for replacement of the body of the mandible. None of the animals who received the ascending ramus and condyle titanium endoprosthesis had an infection. New bone formation was noted around the stems of the titanium devices and inflammatory reaction was much reduced from three to six months. For the polycaprolactone device, more de novo bone formation was seen in the group using Human-BMP-2. Conclusion: The use of a modular endoprosthesis for mandibular reconstruction seemed to result in a physiologic replacement of the lost part of the mandible, although the biomechanics of the system need further evaluation so as to improve its long term stability

In vivo degradation of a new concept of magnesium-based rivet-screws in the minipig mandibular bone

Self-tapping of magnesium screws in hard bone may be a challenge due to the limited torsional strength of magnesium alloys in comparison with titanium. To avoid screw failure upon implantation, the new concept of a rivet-screw was applied to a WE43 magnesium alloy. Hollow cylinders with threads on the outside were expanded inside drill holes of minipig mandibles. During the expansion with a hexagonal mandrel, the threads engaged the surrounding bone and the inside of the screw transformed into a hexagonal screw drive to allow further screwing in or out of the implant. The in vivo degradation of the magnesium implants and the performance of the used coating were studied in a human standard-sized animal model. Four magnesium alloy rivet-screws were implanted in each mandible of 12 minipigs. Six animals received the plasmaelectrolytically coated magnesium alloy implants; another six received the uncoated magnesium alloy rivet-screws. Two further animals received one titanium rivet-screw each as control. In vivo radiologic examination was performed at one, four, and eight weeks. Euthanasia was performed for one group of seven animals (three animals with coated, three with uncoated magnesium alloy implants and one with titanium implant) at 12weeks and for the remaining seven animals at 24weeks. After euthanasia, micro-computed tomography and histological examination with histomorphometry were performed. Significantly less void formation as well as higher bone volume density (BV/TV) and bone-implant contact area (BIC) were measured around the coated implants compared to the uncoated ones. The surface coating was effective in delaying degradation despite plastic deformation. The results showed potential for further development of magnesium hollow coated screws for bone fixation

The use of a polycaprolactone-tricalcium phosphate scaffold for bone regeneration of tooth socket facial wall defects and simultaneous immediate dental implant placement in Macaca fascicularis

Bone regeneration and aesthetic outcomes may be compromised when immediate implants are placed at extraction sites with dehiscence defects. The aim of this study was to compare, in a monkey model, peri-implant bone regeneration and implant stability after immediate implant placement into tooth sockets with facial wall defects in two treatment groups. In eight control monkeys, the bony defect was reconstructed with autogenous particulate bone, whereas in 10 test monkeys a polycaprolactone–tricalcium phosphate (PCL–TCP) scaffold was used. The monkeys were sacrificed after 6 months and the specimens were analyzed by histology and histomorphometry. Better maintenance of facial bone contour was noted in the test group; however, bone regeneration was seen only at areas adjacent to a bony wall of the defect. The mean bone-to-implant contact was 27.6 ± 19.1% (control group) versus 6.8 ± 7.9% (test group). The mean bone area percentage was 11.8 ± 10.1% (control group) versus 6.8 ± 6.9% (test group). Implant survival was 100% at 6 months for both the groups. It was concluded that although the use of a PCL–TCP scaffold showed better maintenance of the alveolar contour as compared to autogenous particulate bone at 6 months, there was minimal bone regeneration within the defect