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Enhancing the function of PLGA-collagen scaffold by incorporating TGF-β1-loaded PLGA-PEG-PLGA nanoparticles for cartilage tissue engineering using human dental pulp stem cells

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Abstract

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 1HNMR, 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.

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Availability of data and materials

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

PBS:

Phosphate-buffered saline

FBS:

Fetal bovine serum

DMEM:

Dulbecco modified Eagle’s medium

h-DPSCs:

Human dental pulp-derived mesenchymal stem cells

ELISA:

Enzyme-linked immunosorbent assay

PLGA-PEG-PLGA:

Poly D, L (lactide-co-glycolide)-b-poly (ethylene glycol)-b-poly D, L (lactide-co-glycolide

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

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Acknowledgements

This project was fulfilled at the Stem Cell Research Center, Tabriz, Iran. The authors would like to thank everybody who assisted us in this regard.

Funding

This investigation was funded by a grant from Tabriz University of Medical Sciences, Tabriz, Iran, Grant No: 64103.

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Parisa Ghandforoushan: conceptualization, methodology, software, investigation, and writing - original; Jalal Hanaee: validation and supervision; Zahra Aghazadeh: methodology, validation, and data curation; Shahin Ahmadian: conceptualization and methodology; Mohammad Samiei: data curation and validation; Amir Mohammad Navali: investigation and writing - reviewing and editing; Ali Khatibi: investigation, software, and data curation; Soodabeh Davaran: conceptualization, methodology, validation, and supervision.

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Correspondence to Soodabeh Davaran.

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Ghandforoushan, P., Hanaee, J., Aghazadeh, Z. et al. Enhancing the function of PLGA-collagen scaffold by incorporating TGF-β1-loaded PLGA-PEG-PLGA nanoparticles for cartilage tissue engineering using human dental pulp stem cells. Drug Deliv. and Transl. Res. 12, 2960–2978 (2022). https://doi.org/10.1007/s13346-022-01161-2

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