Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Medicinal Chemistry, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
Drug Deliv Transl Res. 2022 Dec;12(12):2960-2978. doi: 10.1007/s13346-022-01161-2. Epub 2022 Jun 1.
Since cartilage has a limited capacity for self-regeneration, treating cartilage degenerative disorders is a long-standing difficulty in orthopedic medicine. Researchers have scrutinized cartilage tissue regeneration to handle the deficiency of cartilage restoration capacity. This investigation proposed to compose an innovative nanocomposite biomaterial that enhances growth factor delivery to the injured cartilage site. Here, we describe the design and development of the biocompatible poly(lactide-co-glycolide) acid-collagen/poly(lactide-co-glycolide)-poly(ethylene glycol)-poly(lactide-co-glycolide) (PLGA-collagen/PLGA-PEG-PLGA) nanocomposite hydrogel containing transforming growth factor-β1 (TGF-β1). PLGA-PEG-PLGA nanoparticles were employed as a delivery system embedding TGF-β1 as an articular cartilage repair therapeutic agent. This study evaluates various physicochemical aspects of fabricated scaffolds by HNMR, FT-IR, SEM, BET, and DLS methods. The physicochemical features of the developed scaffolds, including porosity, density, degradation, swelling ratio, mechanical properties, morphologies, BET, ELISA, and cytotoxicity were assessed. The cell viability was investigated with the MTT test. Chondrogenic differentiation was assessed via Alcian blue staining and RT-PCR. In real-time PCR testing, the expression of Sox-9, collagen type II, and aggrecan genes was monitored. According to the results, human dental pulp stem cells (hDPSCs) exhibited high adhesion, proliferation, and differentiation on PLGA-collagen/PLGA-PEG-PLGA-TGFβ1 nanocomposite scaffolds compared to the control groups. SEM images displayed suitable cell adhesion and distribution of hDPSCs throughout the scaffolds. RT-PCR assay data displayed that TGF-β1 loaded PLGA-PEG-PLGA nanoparticles puts forward chondroblast differentiation in hDPSCs through the expression of chondrogenic genes. The findings revealed that PLGA-collagen/PLGA-PEG-PLGA-TGF-β1 nanocomposite hydrogel can be utilized as a supportive platform to support hDPSCs differentiation by implementing specific physio-chemical features.
由于软骨自我再生能力有限,因此治疗软骨退行性疾病一直是矫形医学领域的难题。研究人员一直在仔细研究软骨组织再生,以解决软骨修复能力不足的问题。本研究旨在构建一种创新的纳米复合生物材料,以增强生长因子在受损软骨部位的递送。在这里,我们描述了设计和开发含有转化生长因子-β1(TGF-β1)的生物相容性聚(乳酸-共-乙醇酸)酸-胶原/聚(乳酸-共-乙醇酸)-聚(乙二醇)-聚(乳酸-共-乙醇酸)(PLGA-胶原/PLGA-PEG-PLGA)纳米复合水凝胶。PLGA-PEG-PLGA 纳米粒子被用作包埋 TGF-β1 的递送系统,作为关节软骨修复治疗剂。本研究通过 HNMR、FT-IR、SEM、BET 和 DLS 方法评估了所制备支架的各种物理化学方面。通过孔隙率、密度、降解、溶胀比、机械性能、形态、BET、ELISA 和细胞毒性评估了开发的支架的物理化学特性。通过 MTT 试验研究了细胞活力。通过阿利辛蓝染色和 RT-PCR 评估了软骨分化。在实时 PCR 测试中,监测 Sox-9、胶原 II 型和聚集蛋白聚糖基因的表达。结果表明,与人牙髓干细胞(hDPSCs)相比,PLGA-胶原/PLGA-PEG-PLGA-TGFβ1 纳米复合支架具有更高的粘附、增殖和分化能力。SEM 图像显示 hDPSCs 适合在支架上粘附和分布。RT-PCR 检测数据显示,负载 TGF-β1 的 PLGA-PEG-PLGA 纳米粒子通过表达软骨形成基因在 hDPSCs 中提出成软骨分化。研究结果表明,PLGA-胶原/PLGA-PEG-PLGA-TGF-β1 纳米复合水凝胶可用作支持平台,通过实施特定的物理化学特性来支持 hDPSCs 的分化。