Antibacterial calcium phosphate cement with human periodontal ligament stem cell-microbeads to enhance bone regeneration and combat infection
Gengtao Qiu
Department of Trauma and Joint Surgery, Shunde Hospital, Southern Medical University, Foshan, Guangdong, China
Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, Maryland, USA
Search for more papers by this authorMingguang Huang
Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
Search for more papers by this authorJin Liu
Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, Maryland, USA
Key Laboratory of Shannxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shannxi, China
Search for more papers by this authorPing Wang
Kornberg School of Dentistry, Temple University, Philadelphia, Pennsylvania, USA
Search for more papers by this authorAbraham Schneider
Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, Baltimore, Maryland, USA
Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, USA
Search for more papers by this authorKe Ren
Department of Neural and Pain Sciences, School of Dentistry, Program in Neuroscience, University of Maryland, Baltimore, Maryland, USA
Search for more papers by this authorThomas W. Oates
Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, Maryland, USA
Search for more papers by this authorCorresponding Author
Michael D. Weir
Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, Maryland, USA
Correspondence
Michael D. Weir, Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, Maryland, USA.
Email: [email protected]
Liang Zhao, Department of Trauma and Joint Surgery, Shunde Hospital, Southern Medical University, Foshan, Guangdong, China.
Email: [email protected]
Hockin H. K. Xu, Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, Maryland, USA.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Hockin H. K. Xu
Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, Maryland, USA
Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, USA
Center for Stem Cell Biology and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
Correspondence
Michael D. Weir, Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, Maryland, USA.
Email: [email protected]
Liang Zhao, Department of Trauma and Joint Surgery, Shunde Hospital, Southern Medical University, Foshan, Guangdong, China.
Email: [email protected]
Hockin H. K. Xu, Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, Maryland, USA.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Liang Zhao
Department of Trauma and Joint Surgery, Shunde Hospital, Southern Medical University, Foshan, Guangdong, China
Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
Correspondence
Michael D. Weir, Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, Maryland, USA.
Email: [email protected]
Liang Zhao, Department of Trauma and Joint Surgery, Shunde Hospital, Southern Medical University, Foshan, Guangdong, China.
Email: [email protected]
Hockin H. K. Xu, Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, Maryland, USA.
Email: [email protected]
Search for more papers by this authorGengtao Qiu
Department of Trauma and Joint Surgery, Shunde Hospital, Southern Medical University, Foshan, Guangdong, China
Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, Maryland, USA
Search for more papers by this authorMingguang Huang
Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
Search for more papers by this authorJin Liu
Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, Maryland, USA
Key Laboratory of Shannxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shannxi, China
Search for more papers by this authorPing Wang
Kornberg School of Dentistry, Temple University, Philadelphia, Pennsylvania, USA
Search for more papers by this authorAbraham Schneider
Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, Baltimore, Maryland, USA
Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, USA
Search for more papers by this authorKe Ren
Department of Neural and Pain Sciences, School of Dentistry, Program in Neuroscience, University of Maryland, Baltimore, Maryland, USA
Search for more papers by this authorThomas W. Oates
Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, Maryland, USA
Search for more papers by this authorCorresponding Author
Michael D. Weir
Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, Maryland, USA
Correspondence
Michael D. Weir, Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, Maryland, USA.
Email: [email protected]
Liang Zhao, Department of Trauma and Joint Surgery, Shunde Hospital, Southern Medical University, Foshan, Guangdong, China.
Email: [email protected]
Hockin H. K. Xu, Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, Maryland, USA.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Hockin H. K. Xu
Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, Maryland, USA
Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, USA
Center for Stem Cell Biology and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
Correspondence
Michael D. Weir, Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, Maryland, USA.
Email: [email protected]
Liang Zhao, Department of Trauma and Joint Surgery, Shunde Hospital, Southern Medical University, Foshan, Guangdong, China.
Email: [email protected]
Hockin H. K. Xu, Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, Maryland, USA.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Liang Zhao
Department of Trauma and Joint Surgery, Shunde Hospital, Southern Medical University, Foshan, Guangdong, China
Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
Correspondence
Michael D. Weir, Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, Maryland, USA.
Email: [email protected]
Liang Zhao, Department of Trauma and Joint Surgery, Shunde Hospital, Southern Medical University, Foshan, Guangdong, China.
Email: [email protected]
Hockin H. K. Xu, Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, Maryland, USA.
Email: [email protected]
Search for more papers by this authorMichael D. Weir and Liang Zhao contributed equally to this study.
Abstract
Infectious bone defects remain a significant challenge in orthopedics and dentistry. Calcium phosphate cement (CPC) have attracted significant interest in use as local drug delivery system, which with great potential to control release of antibiotics for the treatment of infectious bone defects. Within the current study, a novel antibacterial scaffold of chitosan-reinforced calcium phosphate cement delivering doxycycline hyclate (CPCC + DOX) was developed. Furthermore, the capacity of CPCC + DOX scaffolds for bone regeneration was enhanced by the human periodontal ligament stem cells (hPDLSCs) encapsulated in alginate beads. CPCC + DOX scaffolds were fabricated to contain different concentrations of DOX. Flexural strength of CPCC + DOX ranged from 5.56 ± 0.70 to 6.2 ± 0.72 MPa, which exceeded the reported strength of cancellous bone. Scaffolds exhibited continual DOX release, reaching 80% at 21 days. Scaffold with 5 mg/ml DOX (CPCC + DOX5mg) had a strong antibacterial effect, with a 4-log colony forming unit reduction against S. aureus and P. gingivalis. The proliferation and osteogenic differentiation of hPDLSCs encapsulated in alginate hydrogel microbeads were investigated in culture with CPCC + DOX scaffolds. CPCC + DOX5mg had no negative effect on proliferation of hPDLSCs. Alkaline phosphatase activity, mineral synthesis, and osteogenic gene expressions for CPCC + DOX5mg group were much higher than control group. DOX did not compromise the osteogenic induction. In summary, the novel CPCC + DOX scaffold exhibited excellent mechanical properties and strong antibacterial activity, while supporting the proliferation and osteogenic differentiation of hPDLSCs. The CPCC + DOX + hPDLSCs construct is promising to enhance bone regeneration and combat bone infections in dental, craniofacial, and orthopedic applications.
CONFLICT OF INTERESTS
No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication.
Supporting Information
| Filename | Description |
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| term3169-sup-0001-fig_s1.pptx736.3 KB | Figure S1 |
| term3169-sup-0002-fig_s2.pptx46.2 KB | Figure S2 |
| term3169-sup-0003-fig_s3.pptx4.7 MB | Figure S3 |
| term3169-sup-0004-fig_s4.pptx369.2 KB | Figure S4 |
| term3169-sup-0005-fig_s5.pptx80.4 KB | Supplementary Figure 5 |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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