Printable Biodegradable Hydrogel with Self-Crosslinking Agents for Wound Dressings

The printed Biomaterial Laboratory at UTEP does research a printable hydrogel which can have appropriate properties for tissue engineering of the skin. Skin is the largest organ in our body which protects us from the environment and pathogens. Skin can be affected by burns and also by diabetic foot ulcers. The current tissue engineered skin substitutes for treatment of diabetic foot ulcers have many shortcomings including difficulty of handling, little if any host integration and not being customizable. The goal of this research is to create a wound care material that helps by integrating with the host tissue. We have been investigating a biodegradable hydrogel which is derived from natural proteins and carbohydrates creating a scaffold to use as a substrate to grow cells. The main components of this hydrogel are gelatin and alginate, both materials with very high biocompatibility and promoting cell proliferation and vascularization. Here we have been studying the oxidation of sodium alginate to generate aldehyde groups that can crosslink the amino group of gelatin and form the biodegradable hydrogel. We also have been investigating the viscosity, gelling time and degree of crosslinking of alginate as a function of pH, degree of oxidation, concentration and temperature. Viscosities for 10% alginate solutions in the range of 5-10cp are obtained, making this material printable. For printable testing we modified an inkjet printer to control the temperature of the cartridge and of the deposition plate. In general, control over the concentrations of alginate as well as the spatial dispensing via printing in a temperature-controlled environment should allow us to generate wound dressings of tunable properties. For future work we will include testing viscosity and printability of alginate adding different types of cells, as fibroblast, keratinocytes and endothelial cell, varying cell concentration. We will also include testing the wound dressing in a small animal model on healing and wound contraction. Introduction Many people suffer from burns and also diabetic foot ulcers. According to the American Burn Association (ABA), in the United States 450,000 people receive medical treatment when they are burned and the survival rate is 94.8% which means that 23,400 people die by burned injuries [1] . The majority of deaths are due to the massive fluid losses and microbial infections [2]. Diabetic foot ulcers are the most common complications of Diabetes mellitus. These kinds of injuries are caused by arterial abnormalities which are too difficult to treat because many complications and infections can be developed by these injuries. These wound are the cause of many foot and leg amputations. Alginate is a carbohydrate extracted from brown algae. It shows good biocompatibility and low toxicity [3]. The oxidation of sodium alginate has been previously studied. It is known that sodium periodate generates aldehyde groups in the modified alginate (MA) which can crosslink with the amino groups of the gelatin [4] with no addition of other chemical agents (like CaCl2). Additionally, the MA shows a good biodegradability which is not observed in the unmodified alginate [5]. The viscosity in the MA decreases and makes it printable (printable biological ink). Gelatin is a polymer derived from collagen which is the principal protein of the skin, and it has been used in medical applications because it shows good biocompatibility and biodegradability [6]. Both alginate and gelatin have many applications in drug delivery, cell therapy, wound dressing, and tissue engineering [7] [8]. Inject printer is the most popular printer because it has a high quality printing at low cost. Inject printing is a contactless technique. The printer receives computer information and reproduces on a substrate [9]. Ink is ejected out of the nozzle as is required, and the amount of printed ink can be controlled [10]. Currently, inkjet printing has been used in biomedical engineering applications (drug screening, biosensors and genomics) [9]. Recently, it was researched cell viability during inkjet printing on biological substrates [11]. The main goal of this research is to create a low cost wound care material that promotes the regeneration of the skin by integration with host tissue using inkjet printing technology. In this research we modified a Hewlett-Packard Deskjet 340 printer and created a biological ink to disperse different types of cells, as fibroblast, keratinocytes, and endothelial to create a biodegradable hydrogel with different cell layers. Materials and Methods Alginic acid sodium salt (medium viscosity) and sodium periodate ACS reagent grade from MP biomedical, gelatin from porcine skin (type A 300 bloom ) from Sigma Aldrich, sodium tetraborate decahydrate (Borax) from Fhisher scientific, phosphate buffered saline (PBS), 2,4,6-trinitrobenzenesulfonic acid (TNBS) from thermo scientific, ethyl alcohol from Pharmco AAPER, Spectra/Por 6 membrane tubing MWCO 2000 from Spectrum laboratories. Alginate Oxidation The alginate was oxidized with sodium periodate to create aldehyde groups in the alginate [12] [13]. 10 g of sodium alginate were dispersed in 25 ml of ethanol and 25 ml of 0.4 M sodium periodate were added. The solution was stirred at room temperature in the dark for 6 h. Water was added to the solution 632 ©2011 Society for Imaging Science and Technology