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

被引:16
作者
Chen, Hong [1 ,2 ,3 ]
Yang, Hui [2 ]
Weir, Michael D. [3 ]
Schneider, Abraham [4 ,5 ]
Ren, Ke [6 ]
Homayounfar, Negar [3 ]
Oates, Thomas W. [3 ]
Zhang, Ke [7 ]
Liu, Jin [3 ,8 ]
Hu, Tao [2 ]
Xu, Hockin H. K. [3 ,5 ,9 ]
机构
[1] Chongqing Med Univ, Coll Stomatol, Dept Endodont, Chongqing Key Lab Oral Dis & Biomed Sci,Chongqing, Chongqing, Peoples R China
[2] Sichuan Univ, West China Hosp Stomatol, Natl Clin Res Ctr Oral Dis, Dept Operat Dent & Endodont,State Key Lab Oral Di, Chengdu, Peoples R China
[3] Univ Maryland, Dept Adv Oral Sci & Therapeut, Dent Sch, Baltimore, MD 21201 USA
[4] Univ Maryland, Dept Oncol & Diagnost Sci, Dent Sch, Baltimore, MD 21201 USA
[5] Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Sch Med, Baltimore, MD 21201 USA
[6] Univ Maryland, Sch Dent, Dept Neural & Pain Sci, Program Neurosci, Baltimore, MD 21201 USA
[7] Capital Med Univ, Sch Stomatol, Dept Orthodont, Beijing, Peoples R China
[8] Xi An Jiao Tong Univ, Coll Stomatol, Key Lab Shannxi Prov Craniofacial Precis Med Res, Xian, Shannxi, Peoples R China
[9] Univ Maryland, Ctr Stem Cell Biol & Regenerat Med, Sch Med, Baltimore, MD 21201 USA
基金
英国科研创新办公室;
关键词
STAPHYLOCOCCUS-AUREUS BIOFILMS; HUMAN INDUCED PLURIPOTENT; UMBILICAL-CORD; DRUG-DELIVERY; IN-VITRO; CEMENT; REGENERATION; COMPOSITE; RELEASE; OSTEOMYELITIS;
D O I
10.1039/d0ra06873j
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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 Staphylococcus aureus (S. aureus) 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 S. aureus, 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 (p < 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.
引用
收藏
页码:40157 / 40170
页数:14
相关论文
共 79 条
[61]   Bone tissue engineering via human induced pluripotent, umbilical cord and bone marrow mesenchymal stem cells in rat cranium [J].
Wang, Ping ;
Liu, Xian ;
Zhao, Liang ;
Weir, Michael D. ;
Sun, Jirun ;
Chen, Wenchuan ;
Man, Yi ;
Xu, Hockin H. K. .
ACTA BIOMATERIALIA, 2015, 18 :236-248
[62]   Strong calcium phosphate cement-chitosan-mesh construct containing cell-encapsulating hydrogel beads for bone tissue engineering [J].
Weir, Michael D. ;
Xu, Hockin H. K. ;
Simon, Carl G., Jr. .
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, 2006, 77A (03) :487-496
[63]   Human bone marrow stem cell-encapsulating calcium phosphate scaffolds for bone repair [J].
Weir, Michael D. ;
Xu, Hockin H. K. .
ACTA BIOMATERIALIA, 2010, 6 (10) :4118-4126
[64]   Treatment of Chronic Bone Infection [J].
Winkler, Heinz ;
Haiden, Peter .
OPERATIVE TECHNIQUES IN ORTHOPAEDICS, 2016, 26 (01) :2-11
[65]   Novel magnetic calcium phosphate-stem cell construct with magnetic field enhances osteogenic differentiation and bone tissue engineering [J].
Xia, Yang ;
Chen, Huimin ;
Zhao, Yantao ;
Zhang, Feimin ;
Li, Xiaodong ;
Wang, Lin ;
Weir, Michael D. ;
Ma, Junqing ;
Reynolds, Mark A. ;
Gu, Ning ;
Xu, Hockin H. K. .
MATERIALS SCIENCE AND ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS, 2019, 98 :30-41
[66]   Fast-setting calcium phosphate scaffolds with tailored macropore formation rates for bone regeneration [J].
Xu, HHK ;
Takagi, S ;
Quinn, JB ;
Chow, LC .
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, 2004, 68A (04) :725-734
[67]   Synergistic reinforcement of in situ hardening calcium phosphate composite scaffold for bone tissue engineering [J].
Xu, HHK ;
Quinn, JB ;
Takagi, S ;
Chow, LC .
BIOMATERIALS, 2004, 25 (06) :1029-1037
[68]  
Xu HHK, 2001, J BIOMED MATER RES, V57, P457, DOI 10.1002/1097-4636(20011205)57:3<457::AID-JBM1189>3.0.CO
[69]  
2-X
[70]   Calcium phosphate cements for bone engineering and their biological properties [J].
Xu, Hockin H. K. ;
Wang, Ping ;
Wang, Lin ;
Bao, Chongyun ;
Chen, Qianming ;
Weir, Michael D. ;
Chow, Laurence C. ;
Zhao, Liang ;
Zhou, Xuedong ;
Reynolds, Mark A. .
BONE RESEARCH, 2017, 5