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一种用于骨组织工程的、可注射的、负载人牙周膜干细胞的抗菌磷酸钙支架。

An antibacterial and injectable calcium phosphate scaffold delivering human periodontal ligament stem cells for bone tissue engineering.

作者信息

Chen Hong, Yang Hui, Weir Michael D, Schneider Abraham, Ren Ke, Homayounfar Negar, Oates Thomas W, Zhang Ke, Liu Jin, Hu Tao, Xu Hockin H K

机构信息

Department of Endodontics, College of Stomatological, Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education Chongqing China.

State Key Laboratory of Oral Diseases, Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, National Clinical Research Centre for Oral Diseases, Sichuan University Chengdu China

出版信息

RSC Adv. 2020 Nov 4;10(66):40157-40170. doi: 10.1039/d0ra06873j. eCollection 2020 Nov 2.

Abstract

Osteomyelitis and post-operative infections are major problems in orthopedic, dental and craniofacial surgeries. It is highly desirable for a tissue engineering construct to kill bacteria, while simultaneously delivering stem cells and enhancing cell function and tissue regeneration. The objectives of this study were to: (1) develop a novel injectable calcium phosphate cement (CPC) scaffold containing antibiotic ornidazole (ORZ) while encapsulating human periodontal ligament stem cells (hPDLSCs), and (2) investigate the inhibition efficacy against () and the promotion of hPDLSC function for osteogenesis for the first time. ORZ was incorporated into a CPC-chitosan scaffold. hPDLSCs were encapsulated in alginate microbeads (denoted hPDLSCbeads). The ORZ-loaded CPCC+hPDLSCbeads scaffold was fully injectable, and had a flexural strength of 3.50 ± 0.92 MPa and an elastic modulus of 1.30 ± 0.45 GPa, matching those of natural cancellous bone. With 6 days of sustained ORZ release, the CPCC+10ORZ (10% ORZ) scaffold had strong antibacterial effects on , with an inhibition zone of 12.47 ± 1.01 mm. No colonies were observed in the CPCC+10ORZ group from 3 to 7 days. ORZ-containing scaffolds were biocompatible with hPDLSCs. CPCC+10ORZ+hPDLSCbeads scaffold with osteogenic medium had 2.4-fold increase in alkaline phosphatase (ALP) activity and bone mineral synthesis by hPDLSCs, as compared to the control group ( < 0.05). In conclusion, the novel antibacterial construct with stem cell delivery had injectability, good strength, strong antibacterial effects and biocompatibility, supporting osteogenic differentiation and bone mineral synthesis of hPDLSCs. The injectable and mechanically-strong CPCC+10ORZ+hPDLSCbeads construct has great potential for treating bone infections and promoting bone regeneration.

摘要

骨髓炎和术后感染是骨科、牙科和颅面外科手术中的主要问题。对于组织工程构建体而言,非常希望其能够杀灭细菌,同时递送干细胞并增强细胞功能和组织再生。本研究的目的是:(1)开发一种新型的可注射磷酸钙骨水泥(CPC)支架,其含有抗生素奥硝唑(ORZ)并封装人牙周膜干细胞(hPDLSCs),以及(2)首次研究其对(此处原文缺失细菌名称)的抑制效果和对hPDLSCs成骨功能的促进作用。将ORZ掺入CPC-壳聚糖支架中。将hPDLSCs封装在海藻酸盐微珠中(记为hPDLSCbeads)。负载ORZ的CPCC+hPDLSCbeads支架完全可注射,其弯曲强度为3.50±0.92MPa,弹性模量为1.30±0.45GPa,与天然松质骨相匹配。随着ORZ持续释放6天,CPCC+10ORZ(10%ORZ)支架对(此处原文缺失细菌名称)具有强大的抗菌作用,抑菌圈为12.47±1.01mm。在CPCC+10ORZ组3至7天未观察到菌落。含ORZ的支架与hPDLSCs具有生物相容性。与对照组相比,在成骨培养基中的CPCC+10ORZ+hPDLSCbeads支架使hPDLSCs的碱性磷酸酶(ALP)活性和骨矿物质合成增加了2.4倍(P<0.05)。总之,这种新型的具有干细胞递送功能的抗菌构建体具有可注射性、良好的强度、强大的抗菌作用和生物相容性,支持hPDLSCs的成骨分化和骨矿物质合成。可注射且机械强度高的CPCC+10ORZ+hPDLSCbeads构建体在治疗骨感染和促进骨再生方面具有巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f214/9057516/77326964c0b3/d0ra06873j-f1.jpg

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