Function and Mechanism of RGD in Bone and Cartilage Tissue Engineering

Yang, Meng; Zhang, Zhengchu; Liu, Yan; Chen, You‐Rong; Deng, Rong‐Hui; Zhang, Zining; Yu, Jia‐Kuo; Yuan, Fu‐Zhen

doi:10.3389/fbioe.2021.773636

Cited by 38 publications

(24 citation statements)

References 104 publications

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“…It has been shown that the RGD motif is a crucial component of adhesive proteins in the ECM, working through integrin transmembrane receptors by transmitting the cell survival signaling within the cells [ 41 ]. However, it has been shown that this tri-peptide exerts controversial issues in cartilage tissue engineering [ 42 ]. It has been demonstrated that the hydrogel modified with RGD peptide (VG-RGD) can be easily injected for the treatment of the intervertebral disc in rats, promoting the proliferation and differentiation of nucleus pulposus (NP)-derived MSCs (NPMSCs), and also promoting the NPMSC’s long-term retention and survival in the degenerated intervertebral disc, with the formation of a neo-ECM [ 38 ].…”

Section: Introductionmentioning

confidence: 99%

RGD-Functionalized Hydrogel Supports the Chondrogenic Commitment of Adipose Mesenchymal Stromal Cells

Manferdini

Trucco

Saleh

et al. 2022

Gels

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Articular cartilage is known to have limited intrinsic self-healing capacity when a defect or a degeneration process occurs. Hydrogels represent promising biomaterials for cell encapsulation and injection in cartilage defects by creating an environment that mimics the cartilage extracellular matrix. The aim of this study is the analysis of two different concentrations (1:1 and 1:2) of VitroGel® (VG) hydrogels without (VG-3D) and with arginine-glycine-aspartic acid (RGD) motifs, (VG-RGD), verifying their ability to support chondrogenic differentiation of encapsulated human adipose mesenchymal stromal cells (hASCs). We analyzed the hydrogel properties in terms of rheometric measurements, cell viability, cytotoxicity, and the expression of chondrogenic markers using gene expression, histology, and immunohistochemical tests. We highlighted a shear-thinning behavior of both hydrogels, which showed good injectability. We demonstrated a good morphology and high viability of hASCs in both hydrogels. VG-RGD 1:2 hydrogels were the most effective, both at the gene and protein levels, to support the expression of the typical chondrogenic markers, including collagen type 2, SOX9, aggrecan, glycosaminoglycan, and cartilage oligomeric matrix protein and to decrease the proliferation marker MKI67 and the fibrotic marker collagen type 1. This study demonstrated that both hydrogels, at different concentrations, and the presence of RGD motifs, significantly contributed to the chondrogenic commitment of the laden hASCs.

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Section: Introductionmentioning

confidence: 99%

RGD-Functionalized Hydrogel Supports the Chondrogenic Commitment of Adipose Mesenchymal Stromal Cells

Manferdini

Trucco

Saleh

et al. 2022

Gels

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show abstract

“…Therefore, the RGD peptide family is considered a suitable candidate for the treatment of multiple diseases and organ regeneration in various tissues. 16 All peptide solutions were prepared with bio-grade sterile deionized water, filtered through 0.22 μm syringe-driven filters (Millipore, USA), and stored at −20°C. The initial concentration of the peptide solution was 10 mg/mL (1%).…”

Section: Methodsmentioning

confidence: 99%

Self-Assembled Nano-Peptide Hydrogels with Human Umbilical Cord Mesenchymal Stem Cell Spheroids Accelerate Diabetic Skin Wound Healing by Inhibiting Inflammation and Promoting Angiogenesis

Xue¹,

Sun²,

Liu³

2022

IJN

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Background Non-healing skin wounds are a common complication in diabetic patients. Vector biomaterials embedded with mesenchymal stem cells (MSCs) are considered a promising treatment approach. In this study, we presented a novel and effective approach to accelerate diabetic skin wound healing. Methods and Materials Human umbilical cord mesenchymal stem cells (hUC-MSCs) were shaped into spheres. RADA16-I, KLT, and RGD nanopeptides were selected for self-assembly into hydrogels. hUC-MSCs spheroids (hUC-MSCsp) were combined in vitro with self-assembled nanopeptide hydrogels and subsequently transplanted into a mouse model of diabetic skin trauma. Results Compared with the PBS, hUC-MSCs, hUC-MSCsp, and hUC-MSCs with hydrogel groups, hUC-MSCsp with hydrogel significantly accelerated wound healing (p<0.01) and shortened the healing time (10 vs 14 vs 21 days). The expressions of IL-6, IL-10, IL-1β, and TNF-α were significantly decreased (p<0.001). The expression of VEGF was significantly higher in the hUC-MSCsp with hydrogel group (p<0.05), and the density of neovascularization in the fresh skin tissue at the wound was also remarkably increased (p<0.01). Conclusion Nanopeptide hydrogels loaded with hUC-MSCsp accelerated diabetic skin wound healing by inhibiting inflammation and promoting angiogenesis compared with conventional stem cell transplantation, which deserves further investigation.

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“…RGD is normally used to improve the bio-inertness of synthetic materials. Indeed, several studies have reported enhanced cell attachment, vitality and enhanced differentiation with biomaterials coated with RGD peptides [103]. To date, RGD peptides suitably immobilized on different biomaterials such as natural (i.e., alginate collagen, hyaluronic acid, cellulose) and synthetic polymers (polyethylene glycol (PEG) or titanium oxide nanotubes) have been associated with the increased biological performance of MSCs in tissue regeneration.…”

Section: Rgd Sequence Peptidesmentioning

confidence: 99%

Multipotential Role of Growth Factor Mimetic Peptides for Osteochondral Tissue Engineering

Rizzo

Palermo

D’Amora

et al. 2022

IJMS

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Articular cartilage is characterized by a poor self-healing capacity due to its aneural and avascular nature. Once injured, it undergoes a series of catabolic processes which lead to its progressive degeneration and the onset of a severe chronic disease called osteoarthritis (OA). In OA, important alterations of the morpho-functional organization occur in the cartilage extracellular matrix, involving all the nearby tissues, including the subchondral bone. Osteochondral engineering, based on a perfect combination of cells, biomaterials and biomolecules, is becoming increasingly successful for the regeneration of injured cartilage and underlying subchondral bone tissue. To this end, recently, several peptides have been explored as active molecules and enrichment motifs for the functionalization of biomaterials due to their ability to be easily chemically synthesized, as well as their tunable physico-chemical features, low immunogenicity issues and functional group modeling properties. In addition, they have shown a good aptitude to penetrate into the tissue due to their small size and stability at room temperature. In particular, growth-factor-derived peptides can play multiple functions in bone and cartilage repair, exhibiting chondrogenic/osteogenic differentiation properties. Among the most studied peptides, great attention has been paid to transforming growth factor-β and bone morphogenetic protein mimetic peptides, cell-penetrating peptides, cell-binding peptides, self-assembling peptides and extracellular matrix-derived peptides. Moreover, recently, phage display technology is emerging as a powerful selection technique for obtaining functional peptides on a large scale and at a low cost. In particular, these peptides have demonstrated advantages such as high biocompatibility; the ability to be immobilized directly on chondro- and osteoinductive nanomaterials; and improving the cell attachment, differentiation, development and regeneration of osteochondral tissue. In this context, the aim of the present review was to go through the recent literature underlining the importance of studying novel functional motifs related to growth factor mimetic peptides that could be a useful tool in osteochondral repair strategies. Moreover, the review summarizes the current knowledge of the use of phage display peptides in osteochondral tissue regeneration.

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Function and Mechanism of RGD in Bone and Cartilage Tissue Engineering

Cited by 38 publications

References 104 publications

RGD-Functionalized Hydrogel Supports the Chondrogenic Commitment of Adipose Mesenchymal Stromal Cells

RGD-Functionalized Hydrogel Supports the Chondrogenic Commitment of Adipose Mesenchymal Stromal Cells

Self-Assembled Nano-Peptide Hydrogels with Human Umbilical Cord Mesenchymal Stem Cell Spheroids Accelerate Diabetic Skin Wound Healing by Inhibiting Inflammation and Promoting Angiogenesis

Multipotential Role of Growth Factor Mimetic Peptides for Osteochondral Tissue Engineering

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