Anti-infective efficacy, cytocompatibility and biocompatibility of a 3D-printed osteoconductive composite scaffold functionalized with quaternized chitosan.
Anti-infective efficacy, cytocompatibility and biocompatibility of a 3D-printed osteoconductive composite scaffold functionalized with quaternized chitosan.
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DOI：
10.1016/j.actbio.2016.09.035
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发表时间：
2016-12
影响因子：
9.7
通讯作者：
Ying Yang;Shengbing Yang;Yu-gang Wang;Zhifeng Yu;Haiyong Ao;Hongbo Zhang;L. Qin;O. Guillaume
中科院分区：
文献类型：
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作者：
Ying Yang;Shengbing Yang;Yu-gang Wang;Zhifeng Yu;Haiyong Ao;Hongbo Zhang;L. Qin;O. Guillaume
污染或感染的骨缺损仍然是临床创伤和骨科的严重挑战，具有骨传导性和抗菌性能的骨替代物代表了治疗策略的改进。本研究将季铵化壳聚糖（羟丙基三甲基氯化铵壳聚糖，HACC）接枝到由聚乳酸-羟基乙酸共聚物（PLGA）和羟基磷灰石（HA）组成的3D打印支架上，以设计具有抗菌和骨传导性能的骨工程支架。我们发现PLGA/HA/HACC和PLGA/HACC复合支架在体外和体内条件下都能减少细菌的粘附和生物膜的形成。ATP渗漏实验表明，HACC固定在支架上可以有效地破坏微生物膜。使用人骨髓来源的间充质干细胞（hBMSCs），我们证明，HA纳入支架，包括PLGA/HA和PLGA/HA/HACC，有利于细胞附着，增殖，扩散和成骨分化相比，HA-自由PLGA或PLGA/HACC支架。最后，在大鼠体内进行的生物相容性试验表明，HA掺入的支架（包括PLGA/HA和PLGA/HA/HACC支架）具有良好的新生血管和组织整合。综上所述，我们的研究结果支持了开发具有潜在临床应用前景的多孔PLGA/HA/HACC复合支架材料的方法，用于感染骨的治疗。重要性声明虽然大量的导电支架生物材料已被开发用于促进感染下的骨再生，但高浓度下潜在的组织毒性和耐药性是它们的主要缺点。该研究表明，采用创新的3D打印技术和共价接枝策略制备的HACC接枝PLGA/HA复合支架显示出显著增强的抗菌活性，特别是对耐药菌株的抗菌活性，以及良好的成骨活性和生物相容性。因此，它为临床治疗感染性骨缺损提供了一种有效的多孔复合支架，降低了细菌耐药的风险，为骨再生和抗感染相关的支架界面改性提供了一种可行的策略。
Contaminated or infected bone defects remain serious challenges in clinical trauma and orthopaedics, and a bone substitute with both osteoconductivity and antibacterial properties represents an improvement for treatment strategy. In this study, quaternized chitosan (hydroxypropyltrimethyl ammonium chloride chitosan, HACC) was grafted to 3D-printed scaffolds composed of polylactide-co-glycolide (PLGA) and hydroxyapatite (HA), in order to design bone engineering scaffolds endowed with antibacterial and osteoconductive properties. We found that both the PLGA/HA/HACC and PLGA/HACC composite scaffolds decreased bacterial adhesion and biofilm formation underin vitroandin vivoconditions. Additionally, ATP leakage assay indicated that immobilizing HACC on the scaffolds could effectively disrupt microbial membranes. Using human bone marrow-derived mesenchymal stem cells (hBMSCs), we demonstrated that HA incorporated scaffolds, including PLGA/HA and PLGA/HA/HACC, favoured cell attachment, proliferation, spreading and osteogenic differentiation compared to HA-free PLGA or PLGA/HACC scaffolds. Finally, anin vivobiocompatibility assay conducted on rats, showed that HA incorporated scaffolds (including PLGA/HA and PLGA/HA/HACC scaffolds) exhibited good neovascularization and tissue integration. Taken together, our findings support the approach for developing porous PLGA/HA/HACC composite scaffold with potential clinical application in the treatment of infected bone.Statement of SignificanceAlthough plenty of conductive scaffold biomaterials have been exploited to improve bone regeneration under infection, potential tissue toxicity under high concentration and antibiotic-resistance are their main deficiencies. This study indicated that HACC-grafted PLGA/HA composite scaffold prepared using an innovative 3D-printing technique and covalent grafting strategy showed significantly enhanced antibacterial activities, especially against the antibiotic-resistant strains, together with good osteogenic activity and biocompatibility. Therefore, it provides an effective porous composite scaffold to combat the infected bone defect in clinic with decreased risks of bacterial resistance and open a feasible strategy for the modification of scaffold interfaces involved in the bone regeneration and anti-infection.