Aligned PVA-BA/AgHAp Nanofiber Composites as Multifunctional Hemostatic, Antimicrobial and Reversibly Adhesive Wound Dressings

Bacterially-induced oral conditions, including periodontitis and dental caries, pose a significant burden on ~45% of the global population.¹ Periodontitis is difficult to treat and can lead to alveolar bone absorption, tooth loss, and potentially even cancer, cardiovascular disease, and inflammatory bowel diseases.² Further, immediate and, sometimes, persistent bleeding may occur after extraction of caries-affected teeth. The goals of the present work, therefore, were to develop a versatile, multifunctional biomaterial with antimicrobial, hemostat, and wound healing properties. A directional freeze-casting technique was employed to fabricate a polyvinyl alcohol-boric acid/silver-doped hydroxyapatite nanoparticles (PVA-BA/AgHAp) aerogel with various PVA-BA/AgHAp mass ratios, where PVA is a biocompatible and biodegradable polymer, while boric acid and AgHAp are expected to provide adhesive³ and antimicrobial functions.⁴ SEM images showed that the directional freeze-casting method resulted in a highly aligned nanofibrillar and porous structure with the pore size from 0.5 to 2 μm, aligned parallel and perpendicular to the freezing direction. The PVA-BA/AgHAp aerogel demonstrated rapid blood absorption and rapid hemostasis as determined by citrated blood clotting assay. The physical aerogel structure provided rapid blood absorption while fibrinogen adsorption on AgHAp induced changes in fibrinogen secondary structure, which was revealed by circular dichroism. We propose that fibrinogen structural changes may promote fibrin formation by Factor IIA, thus enhancing the hemostatic ability. Moreover, upon absorbing water, the aerogel transitioned into a glue-like state, which may provide extensive surface coverage in treating periodontal pockets and dry sockets. Significantly, AgHAp demonstrated broad-spectrum bacterial inhibition, bactericidal activity, and biofilm inhibition against fastidious anaerobic periodontal bacteria (F. nucleatum), caries-causing bacteria (S. mutans), and other bacteria involved in open wound and bone implant infections (S. aureus, S. epidermidis and E. coli). The superior antimicrobial effectiveness is seen because AgHAp releases the antimicrobial agent, soluble Ag⁺, even under anaerobic conditions,⁴ which can diffuse into gum pockets and wounds. The hemostat and antimicrobial properties of the PVA-BA/AgHAp aerogel improved with increasing AgHAp content in the composite. Finally, simple compression of the aerogel perpendicular to the freezing direction resulted in a sheet-like material with reduced porosity than the aerogel, and with reversible adhesion ability due to dynamic boronic-ester bond.³ Upon rehydration, the sheet showed slower swelling rate than the aerogel and transformed into a hydrogel, while retaining reversible adhesion and antimicrobial properties. Thus, the compressed sheet ideal for skin wound dressing application. In conclusion, the directionally freeze-cast PVA-BA/AgHAp composite is a versatile, multifunctional material with combined benefits of rapid hemostasis, reversable adhesion and wide spectrum antimicrobial activity against both fastidious anaerobic bacteria and aerobic bacteria, for treating periodontal, dental, and orthopedic infections as well as skin wound healing.

¹ World Health Organization. (2022). Global oral health status report: towards universal health coverage for oral health by 2030. World Health Organization.
² Qian, Yifeng, et al. "Alveolar bone loss and tooth loss contribute to increase in cancer mortality among older patients." BMC Oral Health 23.1 (2023): 1023.
³ Chen, Mingtao, et al. "Fast, strong, and reversible adhesives with dynamic covalent bonds for potential use in wound dressing." Proceedings of the National Academy of Sciences 119.29 (2022): e2203074119.
⁴ Hu, Ruibo, et al. "Direct, Broad-Spectrum Antimicrobial Activity of Ag+-Doped Hydroxyapatite against Fastidious Anaerobic Periodontal and Aerobic Dental Bacteria." Materials 17.19 (2024): 4688.