Researchers have scrutinized cartilage tissue regeneration to handle the de ciency 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 PLGA-collagen / PLGA-PEG-PLGA nanocomposite scaffold containing 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 1 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, ELIZA, and cytotoxicity were assessed. SEM images displayed suitable cell adhesion and distribution of hDPSCs throughout the scaffolds. The cell viability was investigated with the MTT test. In real-time PCR testing, the expression of Sox-9, collagen type II, and aggrecan genes was monitored. According to the results, h-DPSCs exhibited high adhesion, proliferation, and differentiation on PLGA-collagen/PLGA-PEG-PLGA-TGF-β1 hydrogels compared to the control groups. 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. Due to its potential for the growth and differentiation of hDPSCc, PLGA-collagen/PLGA-PEG-PLGA-TGF-β1 hydrogel is likely to be a suitable biomaterial for cartilage regeneration.