Ibuprofen loaded PLA nanofibrous scaffolds increase proliferation of human skin cells in vitro and promote healing of full thickness incision wounds in vivo

Abstract

This article presents successful incorporation of ibuprofen in polylactic acid (PLA) nanofibers to create scaffolds for the treatment of both acute and chronic wounds. Nanofibrous PLA scaffolds containing 10, 20, or 30 wt % ibuprofen were created and ibuprofen release profiles quantified. In vitro cytotoxicity to human epidermal keratinocytes (HEK) and human dermal fibroblasts (HDF) of the three scaffolds with varying ibuprofen concentrations were evaluated and compared to pure PLA nanofibrous scaffolds. Thereafter, scaffolds loaded with ibuprofen at the concentration that promoted human skin cell viability and proliferation (20 wt %) were evaluated in vivo in nude mice using a full thickness skin incision model to determine the ability of these scaffolds to promote skin regeneration and/or assist with scarless healing. Both acellular and HEK and HDF cell-seeded 20 wt % ibuprofen loaded nanofibrous bandages reduced wound contraction compared with wounds treated with Tegaderm™ and sterile gauze. Newly regenerated skin on wounds treated with cell-seeded 20 wt % ibuprofen bandages exhibited significantly greater blood vessel formation relative to acellular ibuprofen bandages. We have found that degradable anti-inflammatory scaffolds containing 20 wt % ibuprofen promote human skin cell viability and proliferation in vitro, reduce wound contraction in vivo, and when seeded with skin cells, also enhance new blood vessel formation. The approaches and results reported here hold promise for multiple skin tissue engineering and wound healing applications. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 327-339, 2017.

Poly(lactic acid) nanofibrous scaffolds for tissue engineering

“…Electrospun PLA has been used to entrap and deliver drugs that promote wound healing, especially anti-inflammatory and anti-oxidant molecules, and to facilitate non-viral nucleic acid delivery. Drugs such as alkannin, shikonin, curcumin, and ibuprofen have been loaded into electrospun PLA scaffolds to promote cutaneous wound healing [68–70]. It has been shown that curcumin, a plant extract with anti-inflammatory, anti-oxidant, and wound healing properties, loaded into PLA nanofibrous meshes increased the rate of healing of a cutaneous wound in mice compared to either PLA meshes alone or no treatment [69].…”

“…It has been shown that curcumin, a plant extract with anti-inflammatory, anti-oxidant, and wound healing properties, loaded into PLA nanofibrous meshes increased the rate of healing of a cutaneous wound in mice compared to either PLA meshes alone or no treatment [69]. Similarly, ibuprofen-loaded PLA nanofibrous scaffolds support the attachment and proliferation of human epidermal keratinocytes and human dermal fibroblasts [70]. It was also demonstrated in an in vivo full thickness mouse skin incision model that cell-seeded ibuprofen-loaded PLA bandages rescued wound contracture and increased blood vessel formation compared to acellular ibuprofen-loaded PLA bandages [70].…”

“…Similarly, ibuprofen-loaded PLA nanofibrous scaffolds support the attachment and proliferation of human epidermal keratinocytes and human dermal fibroblasts [70]. It was also demonstrated in an in vivo full thickness mouse skin incision model that cell-seeded ibuprofen-loaded PLA bandages rescued wound contracture and increased blood vessel formation compared to acellular ibuprofen-loaded PLA bandages [70]. …”

Electrospun PLGA Nanofiber Scaffolds Release Ibuprofen Faster and Degrade Slower After In Vivo Implantation

“…7, 19, 25, 26, 33 And while some previous studies have tested outcome measures with in vivo application, those studies did not generally evaluate degradation, mechanical, or release properties in serum or in vivo prior to completing in vivo healing studies. 24, 25, 33 Many studies likewise did not evaluate long time points (on the order of months) in vivo , which may explain why some of the issues highlighted in the present findings are not apparent in previous work. One study evaluated how the incorporation of IBP altered scaffold properties, and found similar to our study, that it accelerated the degradation of the scaffold in water.…”

“…25, 33 Numerous investigators have altered the release rate of IBP from polymer scaffolds for particular applications. Incorporation of poly(ethylene glycol)-g-chitosan (PEG-g-CHN) 26 or Labrafil 19 into PLGA attenuates the release of IBP, creating a more sustained release profile.…”