Developing sulfur‐doped titanium oxide nanoparticles loaded chitosan/cellulose‐based proangiogenic dressings for chronic ulcer and burn wounds healing

Abstract Development of biomaterials supporting angiogenesis are highly desired in medical applications. In current work, chitosan and cellulose were cross‐linked by using triethyl orthoformate and loaded with sulfur‐doped titanium oxide nanoparticles. A readily available and inexpensive titanium oxide was added as a potential proangiogenic agent based on our group findings and other reports on metal oxide nanoparticles activity to stimulate angiogenesis. A simple freeze gelation method led to the development of flexible, foldable, and porous membranes. To investigate the chemical characteristics of the synthesized membranes, Fourier‐transform infrared spectroscopy was used. Scanning electron microscopy equipped with energy‐dispersive X‐ray microanalysis was employed for surface morphological investigations. The cross‐linked membranes showed higher degree of swelling capacity compared to the same material with titania‐loaded nanoparticles in vitro. The synthesized materials showed higher degree of degradation in H₂O₂ as compared to phosphate‐buffered saline and lysozyme. Chorioallantoic membrane assay was done to investigate the angiogenic potential. Titanium oxide nanoparticles loaded membranes (CLHTS‐5 wt%) exhibited the best degree of angiogenesis in comparison to the other tested materials. In CLHTS‐5 wt% experimental group, a good level of attachment and ingrowth of several blood vessels was observed. Interestingly, the same tested group (CLHTS‐5 wt%) had shown the increasing trend of cellular metabolic rate of the seeded cells from Day 0 to Day 7 in vitro. These findings were further confirmed by the decline in lactate dehydrogenase enzyme release which was monitored until 72 h, indicating the promising ability of this biomaterial in wound healing applications.