# Modifications of Wound Dressings with Bioactive Agents to Achieve Improved Pro-Healing Properties
## 3 Pro-Healing Wound Dressings
### The Effect of Vitamins on Skin Regeneration  
Unique polymer-based biomaterials can be used as novel drug delivery systems, providing a new treatment strategy of non-healing chronic wounds. A high range of medicinal substances, such as antibiotics, vitamins, growth factors, anti-inflammatory agents, anesthetics, etc., are used in the fabrication of wound dressings in order to alleviate the inflammatory response and support the healing process [71]. Nevertheless, bioactive dressings are most often loaded with antibiotics to fight bacterial invasion or vitamins to support cell proliferation and stimulate wound healing mediators, accelerating the regeneration process. Moreover, vitamin-enriched dressings may reveal antioxidant properties, which are desired in the management of chronic wounds characterized by excessive ROS generation [72; 73]. Vitamins are widely used in various cosmetic products and creams due to their leading significance in wound healing and skincare. Nevertheless, their low bioavailability due to the fast oxidation process results in the high demand for good drug delivery systems. Biomaterial-based drug carriers should be characterized by gradual compound release to overcome the problem of its low bioavailability [74]. Among many vitamins, cocopherol (vitamin E), L-ascorbic acid (vitamin C), and retinol (vitamin A)--which possess anti-inflammatory and anti-oxidant effects--have attracted the greatest attention in the context of wound dressing fabrication. Deficiencies in L-ascorbic acid result in decreased collagen synthesis, impaired angiogenesis, and reduced fibroblast proliferation. Its deficiency is also associated with increased susceptibility to the wound infections because of impaired host immune response [75; 76; 77; 78]. It was proven that vitamin A significantly improves the wound healing process. Retinoic acid formed by the metabolism of retinol increases fibroblast proliferation, however with simultaneous reduction in collagen synthesis [79]. Vitamin E facilitates wound protection against numerous infection and supports wound healing due to its antioxidant properties, stabilization of granulation tissue, and stimulation of re-epithelialization [80; 81]. Bioactive Dressings Enriched with Vitamins  
It is well known that vitamin C is crucial for the wound healing process. In our previous study, it was confirmed that the addition of vitamin C to a chitosan/agarose foam-like dressing supported fibroblast viability and proliferation. Furthermore, biomaterial with incorporated L-ascorbic acid supported PDGF-BB synthesis and had the ability to reduce MMP-2 production by skin fibroblasts [73]. Importantly, [PERSON] et al. [82] described a synergistic effect on the wound closure in a mouse model after application of the dressing material produced by combination of vitamin C and propolisis. Cellulose/PVA film with the addition of propolisis and vitamin C also revealed higher absorption capacity, antibacterial activity against _E. coli_ and _S. aureus_, and controlled vitamin release. Similarly, [PERSON] et al. [83] used vitamin C for the modification of the chitosan-based membrane to achieve accelerated wound healing. The developed biomaterial, which was also loaded with lactic acid, exhibited excellent biocompatibility under in vitro conditions (mouse fibroblast cell line), however vitamin addition negatively affected biomaterial mechanical properties by inducing its fragility. [PERSON] et al. [74] demonstrated positive impact of the vitamin B12 on wound closure in a rat model by application of nanofibrous PCL/gelatin biomaterial as a delivery system. The wound size was reduced by 92.27% in the case of vitamin B12-enriched biomaterial and by only 64.62% when scaffold without vitamin B12 was applied. Moreover, the developed nanofibrous dressing loaded with vitamin B12 had the ability to speed up re-epithelialization process. In turn, [PERSON] et al. [84] investigated the effect of vitamin D3 on the repair process of skin tissue.