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基于脱细胞细胞外基质的各向异性关节软骨生物制造。

Biofabrication of anisotropic articular cartilage based on decellularized extracellular matrix.

作者信息

Puiggalí-Jou Anna, Hui Isabel, Baldi Lucrezia, Frischknecht Rea, Asadikorayem Maryam, Janiak Jakub, Chansoria Parth, McCabe Maxwell C, Stoddart Martin J, Hansen Kirk C, Christman Karen L, Zenobi-Wong Marcy

机构信息

Tissue Engineering + Biofabrication Laboratory, Department of Health Sciences & Technology, ETH Zürich, Otto-Stern-Weg 7, 8093 Zürich, Switzerland.

Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado, 12801 E 17th Ave., Aurora, CO 80045, United States of America.

出版信息

Biofabrication. 2025 Jan 6;17(1). doi: 10.1088/1758-5090/ad9cc2.

DOI:10.1088/1758-5090/ad9cc2
PMID:39757574
Abstract

Tissue-engineered grafts that mimic articular cartilage show promise for treating cartilage injuries. However, engineering cartilage cell-based therapies to match zonal architecture and biochemical composition remains challenging. Decellularized articular cartilage extracellular matrix (dECM) has gained attention for its chondro-inductive properties, yet dECM-based bioinks have limitations in mechanical stability and printability. This study proposes a rapid light-based bioprinting method using a tyrosine-based crosslinking mechanism, which does not require chemical modifications of dECM and thereby preserves its structure and bioactivity. Combining this resin with Filamented Light (FLight) biofabrication enables the creation of cellular, porous, and anisotropic dECM scaffolds composed of aligned microfilaments. Specifically, we focus on the effects of various biopolymer compositions (i.e. hyaluronic acid, collagen I, and dECM) and inner architecture (i.e. bulk light vs FLight) on immune response and cell morphology, and we investigate their influence on nascent ECM production and long-term tissue maturation. Our findings highlight the importance of FLight scaffolds in directing collagen deposition resembling articular cartilage structure and promoting construct maturation, and they emphasize the superiority of biological-rich dECM over single-component materials for engineering articular cartilage, thereby offering new avenues for the development of effective cartilage tissue engineering strategies.

摘要

模仿关节软骨的组织工程移植物在治疗软骨损伤方面显示出前景。然而,设计基于软骨细胞的疗法以匹配区域结构和生化组成仍然具有挑战性。脱细胞关节软骨细胞外基质(dECM)因其软骨诱导特性而受到关注,但基于dECM的生物墨水在机械稳定性和可打印性方面存在局限性。本研究提出了一种基于光的快速生物打印方法,该方法使用基于酪氨酸的交联机制,不需要对dECM进行化学修饰,从而保留其结构和生物活性。将这种树脂与丝状光(FLight)生物制造相结合,能够创建由排列的微丝组成的细胞性、多孔性和各向异性的dECM支架。具体而言,我们关注各种生物聚合物组成(即透明质酸、I型胶原蛋白和dECM)和内部结构(即体光与FLight)对免疫反应和细胞形态的影响,并研究它们对新生细胞外基质产生和长期组织成熟的影响。我们的研究结果突出了FLight支架在引导类似于关节软骨结构的胶原蛋白沉积和促进构建体成熟方面的重要性,并强调了富含生物成分的dECM相对于单一组分材料在工程化关节软骨方面的优越性,从而为开发有效的软骨组织工程策略提供了新途径。

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