Pressure ulcers are a chronic, significant clinical problem without available curative therapies. The goal of this dissertation was to establish an efficacious treatment for healing pressure ulcers. Ultimately, the efficacy of chitosan scaffolds loaded with bFGF in closing pressure ulcers in an aged mouse was determined as a potential therapy for future clinical use.

Initially, the neutrophilic etiology of pressure ulcers was considered when establishing preliminary in vitro studies between chitosan and neutrophils. In particular, the mechanism behind neutrophil migration to chitosan, which was previously uncharacterized, was investigated and found to be a result of IL-8, a potent neutrophil chemokine. Neutrophils secreted increasing levels of IL-8 as N-acetylation of chitosan increased. Although chemotactically attracted to chitosan, neutrophils did not exert any antimicrobial activity towards chitosan, suggesting that the migration was without activation of an inflammatory response. Despite this "inert" migration, the lowest possible N-acetylated chitosan was used for in vivo applications to reduce the risk of potential inflammatory responses by the increased presence of neutrophils.

Next, the effect of interaction between chitosan and fibroblasts were analyzed since chitosan would eventually be placed on dermis, where the predominant cells are fibroblasts. Chitosan scaffolds resulted in lower proliferation rates than polystyrene controls, although fibroblasts grew on both substrates. In addition, fibroblasts were able to produce collagen on chitosan only in the presence of nutrients, implicating the necessity of angiogenic factors in the in vivo deployment of chitosan on pressure ulcers.

Based on these results bFGF, an angiogenic and fibroblast growth factor, was incorporated into chitosan and tested on an aged mouse model of pressure ulcers. Gelatin microparticles were utilized to deliver bFGF within chitosan scaffolds fabricated through freeze-drying processes. Three treatment groups - control gauze, chitosan (CX), and chitosan-bFGF (CX+bFGF) - were established, and the effects of treatment were observed on days 3, 7, and 10. Both CX and CX+bFGF resulted in more wound closure on days 3 and 7. By day 10, all animals exhibited similar wound closure. Lastly, the effect of chitosan on neutrophil elastase, a potent protease, was assessed in vitro and in vivo. In vitro, chitosan decreased elastase activity, suggesting the material could reduce the proteolytic environment of the ulcer. In vivo, CX+bFGF treatment reduced elastase protein levels by day 10, confirming in vitro expectations.

Collectively, this dissertation has:​ 1) established biologically critical rationales for employing chitosan to treat pressure ulcers based on ulcer pathology and wound environments and 2) demonstrated the efficacy of chitosan and bFGF in treating pressure ulcers in an aged mouse model. This body of work presents a potentially beneficial method of treating pressure ulcers in clinical medicine.