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3D 打印双相支架同时再生骨软骨组织。

3D-printed biphasic scaffolds for the simultaneous regeneration of osteochondral tissues.

机构信息

Division of Tissue Engineering and Regeneration Technologies, Department of Applied Biology, Biomedical Technology Wing, Sree Chitra Tirunal Institute of Medical Sciences and Technology, Thiruvananthapuram, Kerala 695012, India.

出版信息

Biomed Mater. 2021 Jul 29;16(5). doi: 10.1088/1748-605X/ac14cb.

Abstract

Osteochondral tissue engineering (OCTE) involves the simulation of highly complex tissues with disparate biomechanical properties. OCTE is regarded as the best option for treating osteochondral defects, most of the drawbacks of current treatment methodologies can be addressed by this method. In recent years, the conventional scaffolds used in cartilage and bone regeneration are gradually being replaced by 3D printed scaffolds (3DP). In the present study, we devised the strategy of 3D printing for fabricating biphasic and integrated scaffolds that are loaded with bioactive factors for enhancing the osteochondral tissue regeneration. Polycaprolactone (PCL) and poly(lactic-co-glycolic acid) (PLGA), is used along with bioactive factors (chondroitin sulphate and beta-tricalcium phosphate (βTCP)) for the upper cartilage and lower bone layer respectively. The 3D printed bi-layered scaffolds with varying infill density, to mimic the native tissue, are not previously explored for OCTE. Hence, we tested the simultaneous osteochondrogenic differentiation inducing potential of the aforesaid 3D printed biphasic scaffolds, using rabbit adipose derived mesenchymal stem cells (ADMSCs). Further, the biphasic scaffolds were highly cytocompatible, with excellent cell adhesion properties and cellular morphology. Most importantly, these biphasic scaffolds directed the simultaneous differentiation of a single stem cell population in to two cell lineages (simultaneous differentiation of rabbit ADMSCs into chondrocytes and osteoblasts). Further, these scaffolds enhanced the production of ECM and induced robust expression of marker genes that is specific for respective cartilage and bone layers. The 3D printed OCTE scaffold of our study hence can simulate the native osteochondral unit and could be potential futuristic biomimetic scaffold for osteochondral defects. Furtherstudies are warranted.

摘要

骨软骨组织工程(OCTE)涉及模拟具有不同生物力学特性的高度复杂组织。OCTE 被认为是治疗骨软骨缺陷的最佳选择,这种方法可以解决当前治疗方法的大多数缺点。近年来,用于软骨和骨再生的传统支架逐渐被 3D 打印支架(3DP)取代。在本研究中,我们设计了 3D 打印制造双相和集成支架的策略,这些支架负载有生物活性因子,以增强骨软骨组织再生。聚己内酯(PCL)和聚(乳酸-共-乙醇酸)(PLGA)与生物活性因子(硫酸软骨素和β-磷酸三钙(βTCP))一起用于上软骨层和下骨层。3D 打印的双层支架具有不同的填充密度,以模拟天然组织,这在 OCTE 中尚未被探索。因此,我们使用兔脂肪间充质干细胞(ADMSCs)测试了上述 3D 打印双相支架同时诱导成骨软骨分化的潜力。此外,双相支架具有高度的细胞相容性,具有良好的细胞粘附特性和细胞形态。最重要的是,这些双相支架指导单个干细胞群体同时向两种细胞谱系分化(兔 ADMSCs 同时分化为软骨细胞和成骨细胞)。此外,这些支架增强了细胞外基质的产生,并诱导了特定于相应软骨和骨层的标记基因的强烈表达。因此,我们研究的 3D 打印 OCTE 支架可以模拟天然骨软骨单元,并且可能是骨软骨缺陷的潜在未来仿生支架。需要进一步研究。

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