Biofabrication of nanocomposite-based scaffolds containing human bone extracellular matrix for the differentiation of skeletal stem and progenitor cells

IF 8.1 1区 医学 Q1 ENGINEERING, BIOMEDICAL Bio-Design and Manufacturing Pub Date : 2024-03-05 DOI:10.1007/s42242-023-00265-z
Yang-Hee Kim, Janos M. Kanczler, Stuart Lanham, Andrew Rawlings, Marta Roldo, Gianluca Tozzi, Jonathan I. Dawson, Gianluca Cidonio, Richard O. C. Oreffo
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Abstract

Autograft or metal implants are routinely used in skeletal repair. However, they fail to provide long-term clinical resolution, necessitating a functional biomimetic tissue engineering alternative. The use of native human bone tissue for synthesizing a biomimetic material ink for three-dimensional (3D) bioprinting of skeletal tissue is an attractive strategy for tissue regeneration. Thus, human bone extracellular matrix (bone-ECM) offers an exciting potential for the development of an appropriate microenvironment for human bone marrow stromal cells (HBMSCs) to proliferate and differentiate along the osteogenic lineage. In this study, we engineered a novel material ink (LAB) by blending human bone-ECM (B) with nanoclay (L, Laponite®) and alginate (A) polymers using extrusion-based deposition. The inclusion of the nanofiller and polymeric material increased the rheology, printability, and drug retention properties and, critically, the preservation of HBMSCs viability upon printing. The composite of human bone-ECM-based 3D constructs containing vascular endothelial growth factor (VEGF) enhanced vascularization after implantation in an ex vivo chick chorioallantoic membrane (CAM) model. The inclusion of bone morphogenetic protein-2 (BMP-2) with the HBMSCs further enhanced vascularization and mineralization after only seven days. This study demonstrates the synergistic combination of nanoclay with biomimetic materials (alginate and bone-ECM) to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalized skeletal tissue repair.

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含有人骨细胞外基质的纳米复合材料支架的生物制造,用于骨骼干细胞和祖细胞的分化
自体移植或金属植入物是骨骼修复的常规方法。然而,它们无法提供长期的临床解决方案,因此需要一种功能性生物仿生组织工程替代方法。利用原生人体骨组织合成生物仿生材料墨水,用于骨骼组织的三维(3D)生物打印,是一种极具吸引力的组织再生策略。因此,人骨细胞外基质(bone-ECM)为人骨髓基质细胞(HBMSCs)沿着成骨系增殖和分化提供了令人兴奋的发展潜力。在这项研究中,我们采用挤压沉积法将人骨-ECM(B)与纳米粘土(L,Laponite®)和海藻酸盐(A)聚合物混合,制成了一种新型材料墨水(LAB)。纳米填料和聚合物材料的加入增加了流变性、可印刷性和药物保留特性,关键是在印刷时保持了 HBMSCs 的活力。含有血管内皮生长因子(VEGF)的基于人骨-ECM 的三维复合构建体在体内外小鸡绒毛膜(CAM)模型中植入后增强了血管生成。在 HBMSCs 中加入骨形态发生蛋白-2(BMP-2),仅七天后就能进一步增强血管生成和矿化。这项研究证明了纳米粘土与生物仿生材料(藻酸盐和骨-ECM)的协同组合可支持体外和体内成骨组织的形成,并为个性化骨骼组织修复提供了一种前景广阔的新型三维生物打印方法。
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来源期刊
Bio-Design and Manufacturing
Bio-Design and Manufacturing Materials Science-Materials Science (miscellaneous)
CiteScore
13.30
自引率
7.60%
发文量
148
期刊介绍: Bio-Design and Manufacturing reports new research, new technology and new applications in the field of biomanufacturing, especially 3D bioprinting. Topics of Bio-Design and Manufacturing cover tissue engineering, regenerative medicine, mechanical devices from the perspectives of materials, biology, medicine and mechanical engineering, with a focus on manufacturing science and technology to fulfil the requirement of bio-design.
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