Novel calcium phosphate cement with biofilm-inhibition and platelet lysate delivery to enhance osteogenesis of encapsulated human periodontal ligament stem cells.

Novel calcium phosphate cement with biofilm-inhibition and platelet lysate delivery to enhance osteogenesis of encapsulated human periodontal ligament stem cells.
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DOI:
10.1016/j.msec.2021.112306
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发表时间:
2021-09
期刊:
Materials science & engineering. C, Materials for biological applications
影响因子:
--
通讯作者:
Zhao L
Zhao L
中科院分区:
其他
文献类型:
--
作者:
Qiu G;Wu H;Huang M;Ma T;Schneider A;Oates TW;Weir MD;Xu HHK;Zhao L

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骨髓炎是由金黄色葡萄球菌(S。金黄色葡萄球菌),伴有进行性骨丢失。本研究首次开发了一种磷酸钙骨水泥(CPC),用于递送强力霉素(DOX)和人血小板裂解物(hPL),以对抗S。金黄色葡萄球菌感染,并增强人牙周膜干细胞(hPDLSCs)的成骨作用。在不存在(CPCC)或存在DOX(CPCC+DOX)的情况下制备含有壳聚糖的CPC支架。此外,将hPL包封在藻酸盐微珠中并掺入CPCC+DOX(CPCC+DOX+ hPL)中。CPCC+DOX+hPL的弯曲强度为(5.56 ± 0.55)MPa,低于CPCC+DOX的(8.26 ± 1.6)MPa(p < 0.05),但超过了文献报道的松质骨强度。CPCC+DOX和CPCC+DOX+hPL对S.金黄色葡萄球菌,使生物膜CFU减少4个数量级。将包封在微珠中的hPDLSC与CPC共培养。hPDLSC能够从微珠中释放,并显示出高增殖率,所有组在14天时增加约8倍。hPL从支架中释放出来,促进hPDLSCs的成骨分化。CPCC+DOX+hPL组ALP活性为28.07 ± 5.15mU/mg,高于CPCC+DOX组的17.36 ± 2.37mU/mg和CPCC组的1.34 ± 0.37mU/mg(p < 0.05)。在第7天,CPCC+DOX+hPL中的成骨基因(ALP、RUNX 2、COL-1和OPN)是对照的3-10倍。CPCC+DOX+hPL组hPDLSC合成骨矿物质的量是CPCC组的3.8倍(p < 0.05)。综上所述,新型CPC+DOX+hPL-hPDLSCs支架具有较强的抗菌活性、良好的细胞相容性和hPDLSCs的成骨分化能力,为骨感染的防治和骨再生的促进提供了新的途径。
Osteomyelitis is caused by Staphylococcus aureus (S. aureus), with associated progressive bone loss. This study developed for the first time a calcium phosphate cement (CPC) for delivery of doxycycline (DOX) and human platelet lysate (hPL) to fight against S. aureus infection and enhance the osteogenesis of human periodontal ligament stem cells (hPDLSCs). Chitosan-containing CPC scaffolds were fabricated in the absence (CPCC) or presence of DOX (CPCC+DOX). In addition, hPL was encapsulated in alginate microbeads and incorporated into CPCC+DOX (CPCC+DOX+ hPL). Flexural strength of CPCC+DOX+hPL was (5.56 ± 0.55) MPa, lower than (8.26 ± 1.6) MPa of CPCC+DOX (p < 0.05), but exceeding the reported strength of cancellous bone. CPCC+DOX and CPCC+DOX+hPL exhibited strong antibacterial activity against S. aureus, reducing biofilm CFU by 4 orders of magnitude. The hPDLSCs encapsulated in microbeads were co-cultured with the CPCs. The hPDLSCs were able to be released from the microbeads and showed a high proliferation rate, increasing by about 8 folds at 14 days for all groups. The hPL was released from the scaffold and promoted the osteogenic differentiation of hPDLSCs. ALP activity was 28.07 ± 5.15 mU/mg for CPCC+DOX+hPL, higher than 17.36 ± 2.37 mU/mg and 1.34 ± 0.37 mU/mg of CPCC+DOX and CPCC, respectively (p < 0.05). At 7 days, osteogenic genes (ALP, RUNX2, COL-1, and OPN) in CPCC+DOX+hPL were 3–10 folds those of control. The amount of hPDLSC-synthesized bone mineral with CPCC+DOX+hPL was 3.8 folds that of CPCC (p < 0.05). In summary, the novel CPC+DOX+hPL-hPDLSCs scaffold exhibited strong antibacterial activity, excellent cytocompatibility and hPDLSC osteogenic differentiation, showing a promising approach for treatment and prevention of bone infection and enhancement of bone regeneration.
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影响因子: --
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