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Current Stem Cell Research & Therapy

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ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

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Research Article

RADA-16-based Self-assembled Peptide Nanofiber Scaffolds Loaded with TGF-β1 Enhance the Chondrogenic Differentiation Potential of BMSCs In vitro

Author(s): Peng Yu, Lian Duan, Zhen Yan, Jun Li and Dao-Zhang Cai*

Volume 19, Issue 2, 2024

Published on: 13 September, 2023

Page: [257 - 266] Pages: 10

DOI: 10.2174/1574888X18666230316112847

Price: $65

Abstract

Objective: At present, cartilage repair does not offer ideal efficacy. Fortunately, recent studies have claimed that RADA-16 peptide is an attractive therapeutic strategy for repairing cartilage defects. Therefore, this study tried to explore the effect of RADA-16 loaded with transforming growth factor-beta (TGF-β) 1 on cartilage differentiation of bone marrow mesenchymal stem cells (BMSCs).

Methods: First, the RADA-16 peptide was synthesized by solid phase peptide, and a well-defined hydrogel was formed by supramolecular peptide self-assembly. Then, TGF-β1 (loading concentration of 10 ng/mL) was loaded into RADA-16, with scanning electron microscopy to observe the morphology of the TGF-β1/RADA-16 hydrogel and detect its related properties. Next, BMSCs were isolated from bone marrow samples and identified. TGF-β1/RADA-16 was co-cultured with L929, BMSCs, and C28/I2 cells, respectively, and the survival and proliferation ability of the cells was determined by live/dead cell staining and MTT assay. Chondrogenic differentiation and sGAG production of BMSCs were determined by Alcian blue staining and Blyscan assay, the expression of cartilage-associated genes by qRT-PCR, and the levels of inflammatory factors by ELISA. As for mechanism investigation, the Smad and ERK/MAPK signaling pathways were detected by western blot.

Results: RADA-16 hydrogel exhibited a well-distributed and interconnected porous surface structure, with a loading rate of 91.9% for TGF-β1. The TGF-β1/RADA-16 hydrogel had good release and degradation properties, and had no negative effect on the survival and proliferation ability of BMSCs, L929, and C28/I2 cells. Importantly, TGF-β1/RADA-16 hydrogel significantly accelerated chondrogenic differentiation and sGAG generation in BMSCs, and decreased pro-inflammatory factor production. In addition, the hydrogel also significantly activated the Smad and ERK/MAPK pathways of BMSCs.

Conclusion: RADA-16 loaded with TGF-β1 has good biological properties and can enhance the chondrogenic differentiation ability of BMSCs.

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[1]
Ojanen SP, Finnilä MAJ, Mäkelä JTA, et al. Anterior cruciate ligament transection of rabbits alters composition, structure and biomechanics of articular cartilage and chondrocyte deformation 2 weeks post-surgery in a site-specific manner. J Biomech 2020; 98: 109450.
[http://dx.doi.org/10.1016/j.jbiomech.2019.109450] [PMID: 31740016]
[2]
Murphy MP, Koepke LS, Lopez MT, et al. Articular cartilage regeneration by activated skeletal stem cells. Nat Med 2020; 26(10): 1583-92.
[http://dx.doi.org/10.1038/s41591-020-1013-2] [PMID: 32807933]
[3]
Maruotti N, Corrado A, Cantatore FP. Osteoblast role in osteoarthritis pathogenesis. J Cell Physiol 2017; 232(11): 2957-63.
[http://dx.doi.org/10.1002/jcp.25969] [PMID: 28425564]
[4]
Andrade R, Vasta S, Pereira R, et al. Knee donor-site morbidity after mosaicplasty – a systematic review. J Exp Orthop 2016; 3(1): 31.
[http://dx.doi.org/10.1186/s40634-016-0066-0] [PMID: 27813019]
[5]
Fu X, Liu G, Halim A, Ju Y, Luo Q, Song AG. Mesenchymal stem cell migration and tissue repair. Cells 2019; 8(8): 784.
[http://dx.doi.org/10.3390/cells8080784] [PMID: 31357692]
[6]
Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284(5411): 143-7.
[http://dx.doi.org/10.1126/science.284.5411.143] [PMID: 10102814]
[7]
Djouad F, Delorme B, Maurice M, et al. Microenvironmental changes during differentiation of mesenchymal stem cells towards chondrocytes. Arthritis Res Ther 2007; 9(2): R33.
[http://dx.doi.org/10.1186/ar2153] [PMID: 17391539]
[8]
Birmingham E, Niebur GL, McHugh PE, Shaw G, Barry FP, McNamara LM. Osteogenic differentiation of mesenchymal stem cells is regulated by osteocyte and osteoblast cells in a simplified bone niche. Eur Cell Mater 2012; 23: 13-27.
[http://dx.doi.org/10.22203/eCM.v023a02] [PMID: 22241610]
[9]
Dallas SL, Rosser JL, Mundy GR, Bonewald LF. Proteolysis of latent transforming growth factor-beta (TGF-beta)-binding protein-1 by osteoclasts. A cellular mechanism for release of TGF-beta from bone matrix. J Biol Chem 2002; 277(24): 21352-60.
[http://dx.doi.org/10.1074/jbc.M111663200] [PMID: 11929865]
[10]
Ji X, Lei Z, Yuan M, et al. Cartilage repair mediated by thermosensitive photocrosslinkable TGFβ1-loaded GM-HPCH via immunomodulating macrophages, recruiting MSCs and promoting chondrogenesis. Theranostics 2020; 10(6): 2872-87.
[http://dx.doi.org/10.7150/thno.41622] [PMID: 32194841]
[11]
Yuan M, Bi B, Huang J, Zhuo R, Jiang X. Thermosensitive and photocrosslinkable hydroxypropyl chitin-based hydrogels for biomedical applications. Carbohydr Polym 2018; 192: 10-8.
[http://dx.doi.org/10.1016/j.carbpol.2018.03.031] [PMID: 29691000]
[12]
He B, Yuan X, Zhang H, Jiang D. Research progress of self-assembling peptide nanofiber scaffold for bone repair. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2014; 28(10): 1303-6.
[PMID: 25591312]
[13]
Jasty S, Suriyanarayanan S, Krishnakumar S. Influence of self-assembling peptide nanofibre scaffolds on retinal differentiation potential of stem/progenitor cells derived from ciliary pigment epithelial cells. J Tissue Eng Regen Med 2017; 11(2): 509-18.
[http://dx.doi.org/10.1002/term.1947] [PMID: 25066608]
[14]
Bagrov D, Gazizova Y, Podgorsky V, et al. Morphology and aggregation of RADA-16-I peptide Studied by AFM, NMR and molecular dynamics simulations. Biopolymers 2016; 106(1): 72-81.
[http://dx.doi.org/10.1002/bip.22755] [PMID: 26501800]
[15]
Zhang S, Holmes TC, DiPersio CM, Hynes RO, Su X, Rich A. Self-complementary oligopeptide matrices support mammalian cell attachment. Biomaterials 1995; 16(18): 1385-93.
[http://dx.doi.org/10.1016/0142-9612(95)96874-Y] [PMID: 8590765]
[16]
Ellis-Behnke RG, Liang YX, Tay DKC, et al. Nano hemostat solution: Immediate hemostasis at the nanoscale. Nanomedicine 2006; 2(4): 207-15.
[http://dx.doi.org/10.1016/j.nano.2006.08.001] [PMID: 17292144]
[17]
Sankar S, O’Neill K, Bagot D’Arc M, et al. Clinical use of the self-assembling peptide RADA16: A review of current and future trends in biomedicine. Front Bioeng Biotechnol 2021; 9: 679525.
[http://dx.doi.org/10.3389/fbioe.2021.679525] [PMID: 34164387]
[18]
Yang X, Zhang Y, Huang C, Lu L, Chen J, Weng Y. Biomimetic hydrogel scaffolds with copper peptide‐functionalized RADA16 nanofiber improve wound healing in diabetes. Macromol Biosci 2022; 22(8): 2200019.
[http://dx.doi.org/10.1002/mabi.202200019] [PMID: 35598070]
[19]
Wang R, Wang Z, Guo Y, Li H, Chen Z. Design of a RADA16-based self-assembling peptide nanofiber scaffold for biomedical applications. J Biomater Sci Polym Ed 2019; 30(9): 713-36.
[http://dx.doi.org/10.1080/09205063.2019.1605868] [PMID: 31018781]
[20]
Velot É, Elkhoury K, Kahn C, et al. Efficient TGF-β1 delivery to articular chondrocytes in vitro using agro-based liposomes. Int J Mol Sci 2022; 23(5): 2864.
[http://dx.doi.org/10.3390/ijms23052864] [PMID: 35270005]
[21]
Liu F, Yuan Y, Bai L, et al. LRRc17 controls BMSC senescence via mitophagy and inhibits the therapeutic effect of BMSCs on ovariectomy-induced bone loss. Redox Biol 2021; 43: 101963.
[http://dx.doi.org/10.1016/j.redox.2021.101963] [PMID: 33865167]
[22]
Liu G, Wu Y, Kong F, Ma S, Fu L, Geng J. BMSCs differentiated into neurons, astrocytes and oligodendrocytes alleviated the inflammation and demyelination of EAE mice models. PLoS One 2021; 16(5): e0243014.
[http://dx.doi.org/10.1371/journal.pone.0243014] [PMID: 33983943]
[23]
Yao Y, Chen R, Wang G, Zhang Y, Liu F. Exosomes derived from mesenchymal stem cells reverse EMT via TGF-β1/Smad pathway and promote repair of damaged endometrium. Stem Cell Res Ther 2019; 10(1): 225.
[http://dx.doi.org/10.1186/s13287-019-1332-8] [PMID: 31358049]
[24]
Busseron E, Ruff Y, Moulin E, Giuseppone N. Supramolecular self-assemblies as functional nanomaterials. Nanoscale 2013; 5(16): 7098-140.
[http://dx.doi.org/10.1039/c3nr02176a] [PMID: 23832165]
[25]
Xu XD, Liang L, Chen CS, et al. Peptide hydrogel as an intraocular drug delivery system for inhibition of postoperative scarring formation. ACS Appl Mater Interfaces 2010; 2(9): 2663-71.
[http://dx.doi.org/10.1021/am100484c] [PMID: 20707334]
[26]
Panek M, Antunović M, Pribolšan L, et al. Bone tissue engineering in a perfusion bioreactor using dexamethasone-loaded peptide hydrogel. Materials 2019; 12(6): 919.
[http://dx.doi.org/10.3390/ma12060919] [PMID: 30893951]
[27]
Vishwakarma A, Bhise NS, Evangelista MB, et al. Engineering immunomodulatory biomaterials to tune the inflammatory response. Trends Biotechnol 2016; 34(6): 470-82.
[http://dx.doi.org/10.1016/j.tibtech.2016.03.009] [PMID: 27138899]
[28]
Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-β family signalling. Nature 2003; 425(6958): 577-84.
[http://dx.doi.org/10.1038/nature02006] [PMID: 14534577]
[29]
Li J, Wang J, Zou Y, et al. The influence of delayed compressive stress on TGF-β1-induced chondrogenic differentiation of rat BMSCs through Smad-dependent and Smad-independent pathways. Biomaterials 2012; 33(33): 8395-405.
[http://dx.doi.org/10.1016/j.biomaterials.2012.08.019] [PMID: 22922021]
[30]
Zhang J, Shi H, Zhang N, Hu L, Jing W, Pan J. Interleukin‐4‐loaded hydrogel scaffold regulates macrophages polarization to promote bone mesenchymal stem cells osteogenic differentiation via TGF‐β1/Smad pathway for repair of bone defect. Cell Prolif 2020; 53(10): e12907.
[http://dx.doi.org/10.1111/cpr.12907] [PMID: 32951298]
[31]
Bobick BE, Kulyk WM. MEK-ERK signaling plays diverse roles in the regulation of facial chondrogenesis. Exp Cell Res 2006; 312(7): 1079-92.
[http://dx.doi.org/10.1016/j.yexcr.2005.12.028] [PMID: 16457813]
[32]
Mao Y, Chen Y, Li W, et al. Physiology‐inspired multilayer nanofibrous membranes modulating endogenous stem cell recruitment and osteo‐differentiation for staged bone regeneration. Adv Healthc Mater 2022; 11(21): 2201457.
[http://dx.doi.org/10.1002/adhm.202201457] [PMID: 36027596]
[33]
Wang Q, Zhou C, Zhang D, et al. The involvement of the ERK-MAPK pathway in TGF-β1–mediated connexin43-gap junction formation in chondrocytes. Connect Tissue Res 2019; 60(5): 477-86.
[http://dx.doi.org/10.1080/03008207.2019.1593394] [PMID: 30897973]

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