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.
Objective This study aimed to observe the cell growth status and multidirectional differentiation ability in a 3D-bioprinted tissue model of self-assembled nanopeptides and human adipose-derived mesenchymal stem cells (Ad-MSCs). Methods Primary Ad-MSCs were isolated, cultured, and identified by flow cytometry. Tissue models were printed via 3D bioprinting technology using a "biological ink" consisting of a mixed solution of self-assembled nanopeptides and Ad-MSCs. Ad-MSCs were induced into osteogenic, adipogenic, and endothelial differentiation and compared with the control groups by staining. Results The nanopeptide fiber was 10-30 nm in diameter and 200-500 nm in length under the atomic-force microscope. It had the characteristics of nano-scale materials. Flow cytometry showed that the isolated and cultured cells were positive for CD29 (98.51%), CD90 (97.87%), and CD166 (98.32%) but did not express CD31 (1.58%), CD34 (2.42%), CD45 (2.95%), or human leukocyte antigen (HLA)-DR (0.53%), consistent with the immunophenotype of Ad-MSCs. Then, a tissue model was printed using the biological ink, followed by induction of differentiation of Ad-MSCs within the tissue model. Alizarin red S staining showed the formation of calcium nodules in the osteogenesis induction experimental group, and oil red O stained lipid droplets in Ad-MSCs in the adipogenesis induction experimental group, whereas the two control groups were not stained. Conclusion Ad-MSCs from primary cultures have the characteristics of stem cells. Self-assembled nanopeptide hydrogel is a good tissue engineering material that can serve as an extracellular matrix. Ad-MSCs in the 3D-printed tissue model using a biological ink consisting of a mixed solution of self-assembled nanopeptides and Ad-MSCs grew well and still had strong differentiation ability.
Objectives: To investigate the transplantation of a functionalized self-assembling nanopeptide hydrogel loaded with adipose-derived mesenchymal stem cells (AD-MSCs) into a rabbit hindlimb ischemia model and to evaluate its effect in promoting vascular regeneration in ischemic tissues.Methods: Functionalized self-assembling nanopeptide hydrogels were synthesized, and the physical and chemical properties of the hydrogels were observed by electron microscopy. Primary AD-MSCs were isolated, cultured, immunophenotyped, induced to differentiate, and verified. The self-assembling nanopeptide hydrogel was combined with mesenchymal stem cells for the three-dimensional culture of AD-MSCs, and the growth characteristics were investigated. Animal models were injected with AD-MSC-loaded self-assembled peptide hydrogel, and the therapeutic effects on arterial ischemia were analyzed.Results: The pore size of the functionalized self-assembling nanopeptide hydrogel was suitable for cell growth. Stem cells had a tendency for migration, differentiation, and angiogenesis in three-dimensional culture. The experimental results of transplantation into the rabbit hindlimb ischemia model showed that the functionalized self-assembling nanopeptide hydrogel loaded with AD-MSCs had better efficacy than AD-MSC transplantation alone.Conclusion: Functionalized self-assembling nanopeptide hydrogels can be used as scaffold materials for three-dimensional culture of AD-MSCs. Functionalized self-assembling peptide hydrogels combined with AD-MSCs have better therapeutic effects than traditional stem cell therapies and can promote vascular regeneration.
The authors have advised that an error was made during the preparation of the AO/EB images shown in Figure 2E on page 2466. All the original data was retained and correct images for the hUC-MSCs, 48h and 72h timepoints were selected as suitable replacements. The corrected Figure 2 is shown below.
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