In vivo evaluation of an ultra-thin polycaprolactone film as a wound dressing.

The use of ultra-thin films as dressings for cutaneous wounds could prove advantageous in terms of better conformity to wound topography and improved vapour transmission. For this purpose, ultra-thin poly(epsilon-caprolactone) (PCL) films of 5-15 microm thickness were fabricated via a biaxial stretching technique. To evaluate their in vivo biocompatibility and feasibility as an external wound dressing, PCL films were applied over full and partial-thickness wounds in rat and pig models. Different groups of PCL films were used: untreated, NaOH-treated, untreated with fibrin, NaOH-treated with perforations, and NaOH-treated with fibrin and S-nitrosoglutathione. Wounds with no external dressings were used as controls. Wound contraction rate, histology and biomechanical analyses were carried out. Wounds re-epithelialized completely at a comparable rate. Formation of a neo-dermal layer and re-epithelialization were observed in all the wounds. A lower level of fibrosis was observed when PCL films were used, compared to the control wounds. Ultimate tensile strength of the regenerated tissue in rats reached 50-60% of that in native rat skin. Results indicated that biaxially-stretched PCL films did not induce inflammatory reactions when used in vivo as a wound dressing and supported the normal wound healing process in full and partial-thickness wounds.

Two-step protocol to incorporate cells in thermoresponsive hydrogels.

One of the stumbling blocks in the formation of a thermoresponsive cell-hydrogel hybrid (TCH) is the efficient incorporation of cells in thermoresponsive hydrogels (TH) using traditional top-down (i.e., cells penetrate in the pre-set gels from top surface) approach. This approach is slow and tedious because the hydrogel needs to soak in the cells culture for a long time to allow cells to penetrate from the gel surface in to the bulk of the gel. In addition, cell incorporation into TH is difficult because elevated dissolution temperatures of gelators are detrimental to cell viability, whereas the highly viscous gel state that formed at ambient temperatures retards the penetration of cells. We propose a bottom-up approach (i.e., cells mixed prior to gel setting) using a novel two-step protocol. The first step is the rapid cooling of the agarose solution from its dissolution temperature (98 degrees C) to 37 degrees C and equilibrating for 3-4 min. The second step is the mixing of fibroblasts with the agarose solution and natural cooling to the room temperature to form the TCH. With this novel protocol, 90% of fibroblasts are found to be trapped in the cell-gel hybrid.

Nitrosoglutathione triggers collagen deposition in cutaneous wound repair.

The presence of nitric oxide (NO) is associated with enhanced wound fibroblast collagen synthesis; previous observations have focused on the effect of NO on wound collagen content. This article emphasizes the effect of nitrosothiols on wound collagen deposition and matrix-metalloproteinase activity, which is the primary breakdown pathway of collagen. We examined the effects of S-nitrosoglutathione (GSNO) and glutathione (GSH) on rat scar tissue. Hydroxyproline content, matrix metalloproteinase activity, total glutathione, and total nitrite of scar tissue were measured 3, 5, 7, and 10 days after wounding. It was observed that, at Day 5 and Day 10, wound collagen content was 52.0 percent and 47.5 percent higher, respectively, after GSNO administration than in controls (p<0.05). GSH administration decreased wound collagen deposition 76.5 percent by Day 5 (p<0.05). GSH lowered the matrix metalloproteinase activity 67 percent at Day 5 and 50 percent (p<0.05) at Day 10. Nitrite and nitrate levels were 55 percent higher in the GSNO treated rats than in the control group (p<0.05) at Day 3, whereas the GSH-treated groups showed no changes. GSNO increased systemic nitrite 53 percent 3 hours after intraperitoneal injection. Our findings suggest that collagen deposition increases in cutaneous wound healing after the administration of GSNO and that this nitrosothiol does not interfere with the collagenolytic pathway, thus maintaining the physiological conditions necessary for wound healing.