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      Bone Regeneration Capability of 3D Printed Ceramic Scaffolds

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          Abstract

          In this study, we evaluated the bone regenerative capability of a customizable hydroxyapatite (HA) and tricalcium phosphate (TCP) scaffold using a digital light processing (DLP)-type 3D printing system. Twelve healthy adult male beagle dogs were the study subjects. A total of 48 defects were created, with two defects on each side of the mandible in all the dogs. The defect sites in the negative control group (sixteen defects) were left untreated (the NS group), whereas those in the positive control group (sixteen defects) were filled with a particle-type substitute (the PS group). The defect sites in the experimental groups (sixteen defects) were filled with a 3D printed substitute (the 3DS group). Six dogs each were exterminated after healing periods of 4 and 8 weeks. Radiological and histomorphometrical evaluations were then performed. None of the groups showed any specific problems. In radiological evaluation, there was a significant difference in the amount of new bone formation after 4 weeks ( p < 0.05) between the PS and 3DS groups. For both of the evaluations, the difference in the total amount of bone after 8 weeks was statistically significant ( p < 0.05). There was no statistically significant difference in new bone between the PS and 3DS groups in both evaluations after 8 weeks ( p > 0.05). The proposed HA/TCP scaffold without polymers, obtained using the DLP-type 3D printing system, can be applied for bone regeneration. The 3D printing of a HA/TCP scaffold without polymers can be used for fabricating customized bone grafting substitutes.

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          Most cited references54

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          Calcium phosphate ceramics in bone tissue engineering: a review of properties and their influence on cell behavior.

          Calcium phosphate ceramics (CPCs) have been widely used as biomaterials for the regeneration of bone tissue because of their ability to induce osteoblastic differentiation in progenitor cells. Despite the progress made towards fabricating CPCs possessing a range of surface features and chemistries, the influence of material properties in orchestrating cellular events such as adhesion and differentiation is still poorly understood. Specifically, questions such as why certain CPCs may be more osteoinductive than others, and how material properties contribute to osteoinductivity/osteoconductivity remain unanswered. Therefore, this review article systematically discusses the effects of the physical (e.g. surface roughness) and chemical properties (e.g. solubility) of CPCs on protein adsorption, cell adhesion and osteoblastic differentiation in vitro. The review also provides a summary of possible signaling pathways involved in osteoblastic differentiation in the presence of CPCs. In summary, these insights on the contribution of material properties towards osteoinductivity and the role of signaling molecules involved in osteoblastic differentiation can potentially aid the design of CPC-based biomaterials that support bone regeneration without the need for additional biochemical supplements.
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            Current State of Fabrication Technologies and Materials for Bone Tissue Engineering

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              Pore size of porous hydroxyapatite as the cell-substratum controls BMP-induced osteogenesis.

              To elucidate the biochemical mechanism of osteogenesis, the effect of matrix geometry upon the osteogenesis induced by bone morphogenetic protein (BMP) was studied. A series of five porous hydroxyapatites with different pore sizes, 106-212, 212-300, 300-400, 400-500, and 500-600 microns, was prepared. A block (approximately 5 x 5 x 1 mm, 40.0 mg) of each hydroxyapatite ceramics was combined with 4 micrograms of recombinant human BMP-2 and implanted subcutaneously into the back skin of rat. Osteoinductive ability of each implant was estimated by quantifying osteocalcin content and alkaline phosphatase activity in the implant up to 4 wk after implantation. In the ceramics of 106-212 microns, the highest alkaline phosphatase activity was found 2 wk after implantation, and the highest osteocalcin content 4 wk after implantation, consistent with the results observed with particulate porous hydroxyapatite [Kuboki, Y. et al. (1995) Connect. Tissue Res. 32: 219-226]. Comparison of the alkaline phosphatase activities at 2 wk and the osteocalcin contents at 4 wk after implantation revealed that the highest amount of bone was produced in the ceramics implants with pore size of 300-400 microns. In the ceramics with smaller or larger pore sizes, the amount of bone formation decreased as the pore size deviated from 300-400 microns. The results indicated that the optimal pore size for attachment, differentiation and growth of osteoblasts and vascularization is approximately 300-400 microns. This study using chemically identical but geometrically different cell substrata is the first demonstration that a matrix with a certain geometrical size is most favorable for cell differentiation.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                08 July 2020
                July 2020
                : 21
                : 14
                : 4837
                Affiliations
                [1 ]Department of Oral and Maxillofacial Surgery, Dentistry, Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068, Korea; kjw9199@ 123456hanmail.net (J.-W.K.); face@ 123456hallym.or.kr (B.-E.Y.)
                [2 ]Graduate School of Clinical Dentistry, Hallym University, Chuncheon 24252, Korea
                [3 ]Department of Otorhinolaryngology-Head & Neck Surgery, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Dongtan 18450, Korea; enthsj@ 123456hanmail.net
                [4 ]Department of Otorhinolaryngology-Head & Neck Surgery, Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068, Korea; pupen@ 123456naver.com
                [5 ]Department of Pathology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Dongtan 18450, Korea; byeon.sunju@ 123456welovedoctor.com
                [6 ]Department of Oral and Maxillofacial Surgery, Dentistry, Korea University Guro Hospital, Seoul 08308, Korea; ungassi@ 123456naver.com
                [7 ]R&D Center, Genoss, Suwon 16229, Korea; soodentist@ 123456naver.com
                [8 ]Department of Oral & Maxillofacial Surgery, School of Dentistry, Seoul National University, Seoul 03080, Korea; leejongh@ 123456snu.ac.kr
                Author notes
                [* ]Correspondence: purheit@ 123456daum.net ; Tel.: +82-10-8787-2640
                Author information
                https://orcid.org/0000-0002-9061-0552
                https://orcid.org/0000-0003-1655-9549
                https://orcid.org/0000-0002-9599-4970
                https://orcid.org/0000-0002-8843-545X
                https://orcid.org/0000-0003-0739-7971
                Article
                ijms-21-04837
                10.3390/ijms21144837
                7402304
                32650589
                c7ff71f8-4d49-42c5-a40b-90ebe93d7ce0
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 30 May 2020
                : 07 July 2020
                Categories
                Article

                Molecular biology
                hydroxyapatite,tricalcium phosphate,3d printing,digital light processing,customizable

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