Temporal regulation of soluble VE-cadherin from endothelialized gene-free scaffold and SDF-1α GAS. SDF-1α GAS strongly affects the vascular growth of endothelial cells by suppressing the release of soluble VE-cadherin. Coculturing with ADSCs offers further control on the release of soluble VE-cadherin from endothelial cells. HUVECs on SDF-1α GAS demonstrated significant reduction in the levels of soluble VE-cadherin at days 7 (p < 0.05) and 10 (p < 0.0005) relative to HUVECs on gene-free scaffold. Coculture on SDF-1α GAS strongly attenuated the release of VE-cadherin at all time points. Data are presented as mean ± standard deviation. One-way ANOVA was used to deduce statistical significance. *, **, ***, and **** indicate statistical significance of p < 0.05, p < 0.01, p < 0.005, and p < 0.0005, respectively
Novel biomaterials can be used to provide a better environment for cross talk between vessel forming endothelial cells and wound healing instructor stem cells for tissue regeneration. This study seeks to investigate if a collagen scaffold containing a proangiogenic gene encoding for the chemokine stromal-derived factor-1 alpha (SDF-1α GAS) could be...
... The lymphangiogenic function increases with infiltrating macrophages that produce (VEGF-C) . In addition to lymphangiogenesis, VEGF-C may regulate physiological angiogenesis [35,36]. Studies have also shown that SIM can suppress the growth of bacterial pathogens [37,38]. ...
Since wound dressing has been considered a promising strategy to improve wound healing, recent attention has been focused on the development of modern wound dressings based on synthetic and bioactive polymers. In this study, we prepared a multifunctional wound dressing based on carboxymethyl chitosan/sodium alginate hydrogel containing a nanostructured lipid carrier in which simvastatin has been encapsulated. This dressing aimed to act as a barrier against pathogens, eliminate excess exudates, and accelerate wound healing by increasing the production of vascular endothelial growth factor (VEGF). Among various fabricated composites of dressing, the hydrogel composite with a carboxymethyl chitosan/sodium alginate ratio of 1:2 had an average pore size of about 98.44 ± 26.9 μm and showed 707 ± 31.9 % swelling and a 2116 ± 79.2 g/m2.per day water vapor transfer rate (WVTR), demonstrating appropriate properties for absorbing exudates and maintaining wound moisture. The nanostructured lipid carrier with optimum composition and properties had a spherical shape and uniform particle size distribution (74.46 ±7.9 nm). The prepared nanocomposite hydrogel displayed excellent antibacterial activity against Escherichia coli and Staphylococcus aureus bacteria as well as high biocompatibility on L929 mouse fibroblast cells. It can release the loaded simvastatin drug slowly and over a prolonged period of time. The highest drug release occurred (80%) within 14 days. The results showed that this novel nanocomposite could be a promising candidate as a wound dressing for treating various chronic wounds in skin tissues.
Wound healing requires a tight orchestration of complex cellular events. Disruption in the cell-signaling events can severely impair healing. The application of biomaterial scaffolds has shown healing potential; however, the potential is insufficient for optimal wound maturation. This study explored the functional impact of a collagen-chondroitin sulfate scaffold functionalized with nanoparticles carrying an anti-aging gene β-Klotho on human adipose-derived stem cells (ADSCs) for rejuvenative healing applications. We studied the response in the ADSCs in three phases: (1) transcriptional activities of pluripotency factors (Oct-4, Nanog and Sox-2), proliferation marker (Ki-67), wound healing regulators (TGF-β3 and TGF-β1); (2) paracrine bioactivity of the secretome generated by the ADSCs; and (3) regeneration of basement membrane (fibronectin, laminin, and collagen IV proteins) and expression of scar-associated proteins (α-SMA and elastin proteins) towards maturation. Overall, we found that the β-Klotho gene-activated scaffold offers controlled activation of ADSCs’ regenerative abilities. On day 3, the ADSCs on the gene-activated scaffold showed enhanced (2.5-fold) activation of transcription factor Oct-4 that was regulated transiently. This response was accompanied by a 3.6-fold increase in the expression of the anti-fibrotic gene TGF-β3. Through paracrine signaling, the ADSCs-laden gene-activated scaffold also controlled human endothelial angiogenesis and pro-fibrotic response in dermal fibroblasts. Towards maturation, the ADSCs-laden gene-activated scaffold further showed an enhanced regeneration of the basement membrane through increases in laminin (2.1-fold) and collagen IV (8.8-fold) deposition. The ADSCs also expressed 2-fold lower amounts of the scar-associated α-SMA protein with improved qualitative elastin matrix deposition. Collectively, we determined that the β-Klotho gene-activated scaffold possesses tremendous potential for wound healing and could advance stem cell-based therapy for rejuvenative healing applications.