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.
J Tissue Eng Regen Med. 2021 Mar;15(3):232-243. doi: 10.1002/term.3169. Epub 2021 Feb 3.
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.
感染性骨缺损仍然是骨科和牙科领域的重大挑战。磷酸钙水泥（CPC）作为局部药物递送系统引起了人们的极大兴趣，它具有控制抗生素释放的巨大潜力，可用于治疗感染性骨缺损。在本研究中，开发了一种新型的壳聚糖增强磷酸钙水泥载多西环素（CPCC+DOX）的抗菌支架。此外，通过将人牙周膜干细胞（hPDLSCs）包封在海藻酸钠珠中来增强 CPCC+DOX 支架的骨再生能力。CPCC+DOX 支架被制成含有不同浓度 DOX 的支架。CPCC+DOX 的弯曲强度范围为 5.56±0.70 至 6.2±0.72 MPa，超过了松质骨的报道强度。支架表现出持续的 DOX 释放，在 21 天达到 80%。含有 5mg/ml DOX 的支架（CPCC+DOX5mg）对金黄色葡萄球菌和牙龈卟啉单胞菌具有很强的抗菌作用，减少了 4 个对数的菌落形成单位。在 CPCC+DOX 支架中培养时，研究了包封在海藻酸钠水凝胶微珠中的 hPDLSCs 的增殖和成骨分化。CPCC+DOX5mg 对 hPDLSCs 的增殖没有负面影响。碱性磷酸酶活性、矿物合成和 CPCC+DOX5mg 组的成骨基因表达均高于对照组。DOX 并未损害成骨诱导。总之，新型 CPCC+DOX 支架具有优异的机械性能和强大的抗菌活性，同时支持 hPDLSCs 的增殖和成骨分化。CPCC+DOX+hPDLSCs 构建体有望增强牙科、颅面和骨科应用中的骨再生和对抗骨感染。
