PurposeNon-healing or slow healing chronic wounds are among serious complications of diabetes that eventually result in amputation of limbs and increased morbidities and mortalities. Chronic diabetic wounds show reduced blood vessel formation (lack of angiogenesis), inadequate cell proliferation and poor cell migration near wounds. In this paper, we report the development of a hydrogel-based novel wound dressing material loaded with reduced graphene oxide (rGO) to promote cell proliferation, cell migration and angiogenesis for wound healing applications.MethodsGelatin-methacryloyl (GelMA) based hydrogels loaded with different concentrations of rGO were fabricated by UV crosslinking. Morphological and physical characterizations (porosity, degradation, and swelling) of rGO incorporated GelMA hydrogel was performed. In vitro cell proliferation, cell viability and cell migration potential of the hydrogels were analyzed by MTT assay, live/dead staining, and wound healing scratch assay respectively. Finally, in vivo chicken embryo angiogenesis (CEO) testing was performed to evaluate the angiogenic potential of the prepared hydrogel.ResultsThe experimental results showed that the developed hydrogel possessed enough porosity and exudate-absorbing capacity. The biocompatibility of prepared hydrogel on three different cell lines (3T3 fibroblasts, EA.hy926 endothelial cells, and HaCaT keratinocytes) was confirmed by in vitro cell culture studies (live/dead assay). The GelMA hydrogel containing 0.002% w/w rGO considerably increased the proliferation and migration of cells as evident from MTT assay and wound healing scratch assay. Furthermore, rGO impregnated GelMA hydrogel significantly enhanced the angiogenesis in the chick embryo model.ConclusionThe positive effect of 0.002% w/w rGO impregnated GelMA hydrogels on angiogenesis, cell migration and cell proliferation suggests that these formulations could be used as a functional wound healing material for the healing of chronic wounds.

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Highlights This review describes how 3D bioprinting can be used for developing patient specific cancer models. Bioprinted cancer models containing patient-derived cancer and stromal cells is promising for personalized cancer therapy screening 3D bioprinted constructs form physiologically relevant cell–cell and cell–matrix interactions. Bioprinted cancer models mimic the 3D heterogeneity of real tumors.

Nonhealing wounds in diabetic patients are a critical challenge, which often cause amputation and mortality. High levels of oxidative stress and aberrations in antioxidant defense mechanisms increase the adverse manifestations of diabetes mellitus. In this study, we developed a biodegradable gelatin methacryloyl (GelMA) hydrogel patch incorporated with cerium oxide nanoparticles (CONPs) for promoting diabetic wound healing. The patches were thoroughly characterized for the morphology, physicomechanical properties, free radical scavenging activity, in vitro cell proliferation, and in vivo diabetic wound healing activity. Highly porous and biodegradable patches showed excellent exudate uptake capacity as evident from the many-fold weight gain (400–700 times) when placed in aqueous medium. Results of free radical scavenging assays clearly indicated that the patches loaded with 1–4% w/w CONPs could effectively inactivate experimentally generated free radicals. Obtained results of in vitro cell culture studies clearly indicated that CONP-incorporated patches could favor the proliferation of skin-associated cells such as keratinocytes and fibroblasts. Results of the wound healing study showed that 1% w/w CONP-loaded patches could effectively improve the healing of wounds in diabetic rats. Overall results indicate that CONP-loaded GelMA hydrogels are highly promising materials for developing clinically relevant patches for treating diabetic wounds.

PurposeImpairment of wound healing is a major issue in type-2 diabetes that often causes chronic infections, eventually leading to limb and/or organ amputation. Connective tissue growth factor (CTGF) is a signaling molecule with several roles in tissue repair and regeneration including promoting cell adhesion, cell migration, cell proliferation and angiogenesis. Incorporation of CTGF in a biodegradable core-shell fiber to facilitate its sustained release is a novel approach to promote angiogenesis, cell migration and facilitate wound healing. In this paper, we report the development of CTGF encapsulated electrospun dual porous PLA-PVA core-shell fiber based membranes for diabetic wound healing applications.MethodsThe membranes were fabricated by a core-shell electrospinning technique. CTGF was entrapped within the PVA core which was coated by a thin layer of PLA. The developed membranes were characterized by techniques such as Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR) and X-Ray Diffraction (XRD) analysis. In vitro cell culture studies using fibroblasts, keratinocytes and endothelial cells were performed to understand the effect of CTGF loaded membranes on cell proliferation, cell viability and cell migration. A chicken chorioallantoic membrane (CAM) assay was performed to determine the angiogenic potential of the membranes.ResultsResults showed that the developed membranes were highly porous in morphology with secondary pore formation on the surface of individual fibers. In vitro cell culture studies demonstrated that CTGF loaded core-shell membranes improved cell viability, cell proliferation and cell migration. A sustained release of CTGF from the core-shell fibers was observed for an extended time period. Moreover, the CAM assay showed that core-shell membranes incorporated with CTGF can enhance angiogenesis.ConclusionOwing to the excellent cell proliferation, migration and angiogenic potential of CTGF loaded core-shell PLA-PVA fibrous membranes, they can be used as an excellent wound dressing membrane for treating diabetic wounds and other chronic ulcers.