A study of the comparative effect of cerium oxide and cerium peroxide on stimulation of angiogenesis: Design and synthesis of pro-angiogenic chitosan/collagen hydrogels.

Poor angiogenesis at injury site is a major problem in chronic wounds, which could lead to limbs amputation in adverse cases. To overcome this issue, several efforts have made in literature and by our group as well to develop pro-angiogenic agents. For this purpose, metal oxides due to their oxidative potential have been studied and found very attractive agents. Cerium oxides are proven to be non-toxic and their biological studies have already proved their importance in preventing chronic inflammation, and neurological diseases among several others by modulating the intracellular reactive oxygen species. In current study, we report the synthesis and neovascularization activity of cerium oxide and cerium peroxide nanoparticles when loaded into chitosan and collagen hydrogel. The hydrogels were characterized by FTIR, SEM and XRD. The pro-angiogenic behavior of these hydrogels was studied by in-vivo CAM assay. It was found that cerium peroxide loaded material showed significantly increase in angiogenesis as compared to cerium oxide loaded materials. It was demonstrated that cerium peroxide hydrogels enhanced the angiogenic capability in CAM assay as compared to cerium oxide and hence holds good potential for chronic ulcer and burn wounds healing.

Oxygen Generating Polymeric Nano Fibers That Stimulate Angiogenesis and Show Efficient Wound Healing in a Diabetic Wound Model.

INTRODUCTION: Diabetic wounds are challenging to treat due to a wide range of pathophysiological changes. Hypoxia is one of the predominant contributing factors of poor vascularization and chronicity in diabetic wounds. This study was designed to develop polycaprolactone (PCL)-based oxygen-releasing electrospun wound dressings and evaluate their efficacy for improved full thickness wound healing in diabetic rats. METHODS: PCL-based oxygen releasing wound dressings were made using electrospinning technology. The developed dressings were characterized in terms of physical as well as biological properties both in vitro and in vivo. E-spun nanofibrous dressings were physically characterized with scanning electron microscopy, Fourier-transform infrared spectroscopy, and Energy-dispersive X-ray spectroscopy. To study the likely impact of the fabricated wound dressings in hypoxic conditions, HIF-1α expression analysis was carried out both at gene and protein levels. Wound dressings were further evaluated for their healing potential for extensive wounds in diabetic rat models. RESULTS: The experimental results showed that the developed dressings were capable of continuously generating oxygen for up to 10 days. Cell studies further confirmed pronounced expression of HIF-1α at gene and protein levels in cells seeded on PCL-sodium percarbonate (SPC) and PCL scaffolds compared with the cells cultured on a tissue culture plate. Chorioallantoic membrane assay revealed the supportive role of oxygen releasing dressings on angiogenesis compared to the control group. Histological assessment of the regenerated skin tissues proved that full thickness wounds covered with SPC loaded PCL dressings had a comparatively better vascularized and compact extracellular matrix with completely covered thick epithelium. DISCUSSION: The developed oxygen generating polymeric nanofibrous wound dressings could potentially be used as an envisioned approach for the efficient recovery of chronic diabetic wounds.

Novel chitosan derivative based composite scaffolds with enhanced angiogenesis; potential candidates for healing chronic non-healing wounds.

The success of wound healing depends upon the proper growth of vascular system in time in the damaged tissues. Poor blood supply to wounded tissues or tissue engineered grafts leads to the failure of wound healing or rejection of grafts. In present paper, we report the synthesis of novel organosoluble and pro-angiogenic chitosan derivative (CSD) by the reaction of chitosan with 1,3-dimethylbarbituric acid and triethylorthoformate (TEOF). The synthesized material was characterized by FTIR and 13C-NMR to confirm the incorporated functional groups and new covalent connectivities. Biodegradability of the synthesized chitosan derivative was tested in the presence of lysozyme and was found to be comparable with CS. The cytotoxicity and apoptosis effect of new derivative was determined against gastric adenocarcinoma (AGS) cells and was found to be non-toxic. The CSD was found to be soluble in majority of organic solvents. It was blended with polycaprolactone (PCL) to form composite scaffolds. From an ex ovo CAM assay, it was noted that CSD stimulated the angiogenesis.