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具有软骨生成和成骨特性的脱细胞软骨生物活性固体泡沫支架的研制。

Development of bioactive solid-foam scaffolds from decellularized cartilage with chondrogenic and osteogenic properties.

作者信息

Mendibil Unai, Lópiz-Morales Yaiza, Arnaiz Blanca, Ruiz-Hernández Raquel, Martín Pablo, Di-Silvio Desiré, Garcia-Urquia Nerea, Elortza Felix, Azkargorta Mikel, Olalde Beatriz, Abarrategi Ander

机构信息

Center for Cooperative Research in Biomaterials (CIC BiomaGUNE), Basque Research and Technology Alliance (BRTA), 20014, Donostia-San Sebastian, Spain.

TECNALIA, Basque Research and Technology Alliance (BRTA), 20009, Donostia-San Sebastian, Spain.

出版信息

Mater Today Bio. 2024 Sep 3;28:101228. doi: 10.1016/j.mtbio.2024.101228. eCollection 2024 Oct.

Abstract

Full osteochondral regeneration remains a major clinical challenge. Among other experimental cartilage regenerative approaches, decellularized cartilage (DCC) is considered a promising material for generating potentially implantable scaffolds useful as cartilage repair strategy. In this work, we focus on screening and comparing different decellularization methods, aiming to generate DCC potentially useful in biomedical context, and therefore, with biological activity and functional properties in terms of induction of differentiation and regeneration. Data indicates that enzymatic and detergents-based decellularization methods differentially affect ECM components, and that it has consequences in further biological behavior. SDS-treated DCC powder is not useful to be further processed in 2D or 3D structures, because these structures tend to rapidly solubilize, or disaggregate, in physiologic media conditions. Conversely, Trypsin-treated DCC powders can be processed to mechanically stable 2D films and 3D solid-foam scaffolds, presumably due to partial digestion of collagens during decellularization, which would ease crosslinking at DCC during solubilization and processing. cell culture studies indicate that these structures are biocompatible and induce and potentiate chondrogenic differentiation. implantation of DCC derived 3D porous scaffolds in rabbit osteochondral defects induce subchondral bone regeneration and fibrocartilage tissue formation after implantation. Therefore, this work defines an optimal cartilage tissue decellularization protocol able to generate DCC powders processable to biocompatible and bioactive 2D and 3D structures. These structures are useful for cartilage research and subchondral bone regeneration, while hyaline cartilage regeneration with DCC alone as implantable material remains elusive.

摘要

全层骨软骨再生仍然是一项重大的临床挑战。在其他实验性软骨再生方法中,脱细胞软骨(DCC)被认为是一种有前景的材料,可用于制造潜在可植入的支架,作为软骨修复策略。在这项工作中,我们专注于筛选和比较不同的脱细胞方法,旨在生成在生物医学背景下可能有用的DCC,因此,在诱导分化和再生方面具有生物活性和功能特性。数据表明,基于酶和洗涤剂的脱细胞方法对细胞外基质(ECM)成分有不同影响,并且这会对进一步的生物学行为产生影响。经十二烷基硫酸钠(SDS)处理的DCC粉末无法进一步加工成二维或三维结构,因为这些结构在生理介质条件下往往会迅速溶解或分解。相反,经胰蛋白酶处理的DCC粉末可以加工成机械稳定的二维薄膜和三维固体泡沫支架,这可能是由于脱细胞过程中胶原蛋白的部分消化,这将在溶解和加工过程中使DCC更容易交联。细胞培养研究表明,这些结构具有生物相容性,并能诱导和增强软骨形成分化。将源自DCC的三维多孔支架植入兔骨软骨缺损处,植入后可诱导软骨下骨再生和纤维软骨组织形成。因此,这项工作定义了一种最佳的软骨组织脱细胞方案,能够生成可加工成生物相容性和生物活性二维及三维结构的DCC粉末。这些结构可用于软骨研究和软骨下骨再生,而仅使用DCC作为可植入材料实现透明软骨再生仍然难以实现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/251f/11408866/95c410f8589b/ga1.jpg

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