Fabrication and Characterization of a Nitric Oxide-Releasing Nanofibrous Gelatin Matrix

Abstract

Nitric oxide (NO) plays an important role in cardiovascular homeostasis, immune responses, and wound repair. The pro-angiogenic and antimicrobial properties of NO has stimulated the development of NO-releasing materials for wound dressings. Gelatin, an abundant natural biodegradable polymer derived from collagen, is able to promote wound repair. S-Nitroso-N-acetylpenicillamine (SNAP) can release NO under physiological conditions and when exposed to light. The objective of this project was to fabricate a NO-releasing gelatin-based nanofibrous matrix with precise light-controllable ability. Results showed that under controlled phase separation fabrication conditions, the gelatin formed a highly porous matrix with the nanofiber diameter ranging from 50 to 500 nm. Importantly, the removal of the trace amount of divalent metal ions within gelatin generated a more stable nanofibrous structure. N-acetyl-D-penicillamine (NAP) was functionalized onto the matrix and nitrosated with t-butyl nitrite, yielding a SNAP-gelatin matrix. Analysis of the photoinitiated NO-release showed that the SNAP-gelatin matrices released NO in a highly controllable manner. Application of increasing light intensities yielded increased NO flux from the matrices. In addition, the dried matrices stored in dark at 4 °C maintained stable NO storage capacity, and the purified (ion-removed) gelatin preserved higher NO-releasing capacity than nonpurified gelatin. The antibacterial effect from the SNAP-gelatin matrices was demonstrated by exposing Staphylococcus aureus ( S. aureus ) to a light-triggered NO flux. This controllable NO-releasing scaffold provides a potential antibacterial therapeutic approach to combat drug resistant bacteria.

Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO)

“…To improve the NO payload and stability, achieve targeted NO delivery through multi-functionalization and elongate NO releasing lifetime, many different scaffolds have been used as NO-releasing or NO-generating vehicles. These include micelles, 138,190,191 microbubbles, 192 proteins, 193–197 liposomes, 126,198 inorganic nanoparticles (such as silica, 70,199–203 gold, 204,205 microparticles, 198,206 zeolites, 207,208 ), metal-organic frameworks (MOFs), 209–212 dendrimers, 71,213,214 xerogels, 215–217 electrospun fibers, 88,100,218 natural polymers (chitosan, 85–87,219–221 gelatin, 222 etc. ), and other organic polymers (polymethacrylate, 223 polyester, 224,225 polydimethylsiloxane (PDMS), 226 polysaccharides, 227,228 hydrogel, 178,179,229,230 PVA, 49,231,232 polyurethanes, 161,162,233,234 and PVC 154 ).…”

“…Evidence suggested that 67 % of the photoinitiated NO was accounted for by the longer wavelength (590 nm) and 33 % by shorter wavelengths (centered around 340 nm). SNAP has also been covalently attached to PDMS, 226 gelatin 222 and a macrocycle (e.g., cyclam). 243 The ability to generate programmable sequences of NO flux from these light-sensitive materials can offer precise spatial and temporal control of the NO release and potentially provides a platform to systematically study, at a fundamental level, the in vivo physiological response to implanted devices.…”

“…Frost et al successfully develop a S -nitroso- N -acetyl-D-penicillamine functionalized polymer matrix (e.g., PDMS, 226 cyclam 243 and gelatin 222 ) that can release NO via light-initiated SNAP decomposition. SNAP modified purified gelatin can release NO up to 1 × 10 −8 µmol mg −1 s −1 under a 527 nm wavelength light-emitting diode (LED,) and it also shows continuous and light intensity-responsive NO release over 24 h, with a total payload of 0.06 µmol NO mg −1 .…”

LbL Assembly of Albumin on Nitric Oxide-Releasing Silica Nanoparticles Using Suramin, a Polyanion Drug, as an Interlayer Linker

“…Various nano platforms have been proved successful in delivering NO. [14][15][16][17][18][19][20][21] Remarkably, these NO-releasing NPs exhibit a wide range of potential therapeutic activities, including antitumor effect. [22][23][24][25] In the present study, NO-releasing 4 S-nitroso silica NPs (SNO-SiNPs) were prepared from a single silane source using a surfactantfree and energy-efficient approach.…”

Nanolayer formation on titanium by phosphonated gelatin for cell adhesion and growth enhancement

“…8,[37][38][39][40] Here, titaniumand cell-adhesive gelatin was prepared by chemical modification with phosphate groups as a biological approach to enhance cell functions on titanium surfaces. We found that the gelation temperature was reduced by the modification and time-of-flight secondary ion mass spectrometry (ToF-SIMS) showed direct bonding between the phosphonated gelatin and the titanium surface.…”