Biomechanically matched and multistage hybrid porous scaffolds for stem cell-based osteochondral regeneration

IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
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Abstract

Osteochondral tissue has limited self-repair ability owing to its ischemic microenvironment and mechanically challenging conditions. Cell-based tissue engineering, a promising strategy for osteochondral regeneration, is influenced by the osteochondral-inducing scaffolds, such as bioactive agents and bionic microstructures, and mechanical properties. The current platforms are unsatisfactory because they fail to match the mechanical strength of natural osteochondral tissue while retaining high porosity and bioactivity. Hence, we developed growth factor-free multistage porous hybrid scaffolds composed of poly(lactic-co-glycolic acid) (PLGA) backbones with milli-micrometer two-stage pores and bioactive poly(γ-ethyl-l-glutamate) (PELG) thermo-responsive hydrogel. Highly porous pure PLGA backbones with controllable pore structures and tunable mechanical strength were prepared using low-temperature deposition modeling 3D printing and salt-leaching method with sodium chloride (NaCl) as a porogen. The arginine-glycine-aspartic acid (RGD) peptide and the chondrogenic molecule kartogenin (KGN) were conjugated to the terminals of poly(ethylene glycol) and PELG to enhance cell proliferation and induce cartilage differentiation, respectively. Moreover, the multistage PLGA/RGDPELGKGN porous hybrid scaffolds provided conducive environments for the proliferation and chondrogenesis of peripheral blood-derived mesenchymal stem cells (PBMSCs) and successfully repaired critical-sized osteochondral defects in the rabbit femoral trochlea, indicating its clinical potential for osteochondral repair.
用于干细胞骨软骨再生的生物力学匹配多级混合多孔支架
骨软骨组织由于其缺血微环境和具有机械挑战性的条件,自我修复能力有限。基于细胞的组织工程是一种很有前景的骨软骨再生策略,它受到骨软骨诱导支架(如生物活性剂和仿生微结构)和机械性能的影响。目前的平台不能令人满意,因为它们无法在保持高孔隙率和生物活性的同时,达到天然骨软骨组织的机械强度。因此,我们开发了不含生长因子的多级多孔混合支架,由具有毫微米级两级孔隙的聚乳酸-共聚乙醇酸(PLGA)骨架和生物活性聚γ-乙基-谷氨酸(PELG)热响应水凝胶组成。以氯化钠(NaCl)为成孔剂,采用低温沉积建模三维打印和盐浸法制备了具有可控孔隙结构和可调机械强度的高多孔纯聚乳酸乙二胺(PLGA)骨架。精氨酸-甘氨酸-天冬氨酸(RGD)肽和软骨生成分子卡托原蛋白(KGN)分别被连接到聚乙二醇和PELG的末端,以增强细胞增殖和诱导软骨分化。此外,多级PLGA/RGDPELGKGN多孔杂化支架为外周血间充质干细胞(PBMSCs)的增殖和软骨生成提供了有利的环境,并成功修复了家兔股骨蹄部临界大小的骨软骨缺损,显示了其在骨软骨修复方面的临床潜力。
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来源期刊
Nano Today
Nano Today 工程技术-材料科学:综合
CiteScore
21.50
自引率
3.40%
发文量
305
审稿时长
40 days
期刊介绍: Nano Today is a journal dedicated to publishing influential and innovative work in the field of nanoscience and technology. It covers a wide range of subject areas including biomaterials, materials chemistry, materials science, chemistry, bioengineering, biochemistry, genetics and molecular biology, engineering, and nanotechnology. The journal considers articles that inform readers about the latest research, breakthroughs, and topical issues in these fields. It provides comprehensive coverage through a mixture of peer-reviewed articles, research news, and information on key developments. Nano Today is abstracted and indexed in Science Citation Index, Ei Compendex, Embase, Scopus, and INSPEC.
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