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Up to present, many advantages have been achieved in the field of cell-based therapies by applying sophisticated methodologies and delivery approaches. Microcapsules are capable to provide safe microenvironment for cells during transplantation in a simulated physiological 3D milieu. Here, we aimed to investigate the effect of alginate-gelatin encapsulation on angiogenic behavior of human endothelial cells over a period of 5 days. Human umbilical vein endothelial cells were encapsulated by alginate-gelatin substrate and incubated for 5 days. MTT and autophagy PCR array analysis were used to monitor cell survival rate. For in vitro angiogenesis analysis, cell distribution of Tie-1, Tie-2, VEGFR-1, and VEGFR-2 were detected by ELISA. In addition to in vitro tubulogenesis assay, we monitored the expression of VE-cadherin by Western blotting. The migration capacity of encapsulated HUVECs was studied by measuring MMP-2 and MMP-9 via gelatin zymography. The in vivo angiogenic potential of encapsulated HUVECs was analyzed in immune-compromised mouse implant model during 7 days post-transplantation. We demonstrated that encapsulation promoted HUVECs cell survival and proliferation. Compared to control, no significant differences were observed in autophagic status of encapsulated cells (p > 0.05). The level of Tie-1, Tie-2, VEGFR-1, and VEGFR-2 were increased, but did not reach to significant levels. Encapsulation decreased MMP-2, -9 activity and increased the VE-cadherin level in enclosed cells (p < 0.05). Moreover, an enhanced in vivo angiogenic response of encapsulated HUVECs was evident as compared to non-capsulated cells (p < 0.05). These observations suggest that alginate-gelatin encapsulation can induce angiogenic response in in vivo and in vitro conditions.

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To develop an efficient injectable alginate‐based hydrogel for soft tissue engineering applications, phenol moiety (Ph) was introduced into alginate (Alg‐Ph), and the influence of gelatin as cell adhesive molecule was evaluated on the peroxidase‐mediated alginate hydrogel properties and cultured chondrocytic cell behavior. Addition of gelatin (1.5% w/v) to Alg‐Ph (1.5% w/v) hydrogels (Alg‐Ph/gelatin) regulated characteristics of the enzymatically gellable alginate hydrogel with increasing gelation time to 5.1 min (76%). Swelling ratio and degradation rates of the Alg‐Ph/gelatin hydrogel also increased 60 and 100%, respectively, while the mechanical strength value was 35% less than the Alg‐Ph hydrogel. Scanning electron microscopy images showed that the addition of gelatin could also increase uniformity of pore sizes inside the Alg‐Ph/gelatin hydrogels. The chondrocyte cells maintained their original phenotype and revealed statistically more metabolic activities in the Alg‐Ph/gelatin hydrogel. Hydrogels subscutaneously implanted in rats could also be identified readily without complete absorption and signs of toxicity or any untoward reactions after 1 month. Viable chondrocyte cells inside globular aggregates were seen as red colored areas in the cell‐laden hydrogels. The study demonstrates that enzymatically gellable alginate/gelatin hydrogel has fair potential as a natural‐based injectable hydrogel for soft tissue engineering applications.

Background Microcapsule is considered as a promising 3D microenvironment for Bone Tissue Engineering (BTE) applications. Microencapsulation of cells in an appropriate scaffold not only protected the cells against excess stress but also promoted cell proliferation and differentiation. Through the current study, we aimed to microcapsulate the human Dental Pulp Stem Cells (hDPSCs) and evaluated the proliferation and osteogenic differentiation of those cells by using MTT assay, qRT-PCR, Alkaline phosphatase, and Alizarine Red S. Results The SEM results revealed that Alg/Gel microcapsules containing nHA showed a rough and more compact surface morphology in comparison with the Alg/Gel microcapsules. Moreover, the microencapsulation by Alg/Gel/nHA could improve cell proliferation and induce osteogenic differentiation. The cells cultured in the Alg/Gel and Alg/Gel/nHA microcapsules showed 1.4-fold and 1.7-fold activity of BMP-2 gene expression more in comparison with the control group after 21 days. The mentioned amounts for the BMP-2 gene were 2.5-fold and 4-fold more expression for the Alg/Gel and Alg/Gel/nHA microcapsules after 28 days. The nHA, addition to hDPSCs-laden Alg/Gel microcapsule, could up-regulate the bone-related gene expressions of osteocalcin, osteonectin, and RUNX-2 during the 21 and 28 days through the culturing period, too. Calcium deposition and ALP activities of the cells were observed in accordance with the proliferation results as well as the gene expression analysis. Conclusion The present study demonstrated that microencapsulation of the hDPSCs inside the Alg/Gel/nHA hydrogel could be a potential approach for regenerative dentistry in the near future. Graphical abstract