Preclinical evaluation of collagen type Ⅰ scaffolds that include gelatin-collagen microparticles and are loaded with an aqueous aloe vera extract in a rodent model of full-thickness skin wound

摘要

Scaffolds that support tissue growth can also be designed to control the release of plant extracts commonly used as wound healing agents. We have developed collagen type Ⅰ scaffolds containing microparticles of gelatin-collagen (CS-GC) that in vitro sustain the release of non-cytotoxic concentrations of an extract of Aloe vera during a span of time that matches the in vivo remodeling stages of skin healing. Worldwide, mucilage gel and extracts of this plant are used topically on skin as moisturizers, antiseptica, anti-inflammatories, etc. The use of A vera preparations to promote skin wound healing has been approved by The Colombian Drug Regulatory Agency (INVIMA). Here, we report on a pre-clinical evaluation of the performance of a CS-GC loaded with an aqueous extract of A. vera mucilage gel in a Cavia porcellus wound model. Thirty guinea pigs were divided in six groups, of five animals each. Three groups had two contralateral acute full-thickness wounds of 1 cm~2 (small wound); the remaining three had bigger (3cm2) full-thickness wounds (large wound). One small wound group and one large wound group were grafted on one side with CS-GC. Another small wound group and large wound group were grafted with CS-GC loaded with the aqueous extract of A. vera (CS-GCE). The two remaining groups were treated with gelatin-collagen microparticles loaded with the plant extract. In all cases contralateral wounds were left to close by secondary intention (control). Clinical follow-ups were made at 7,15,21, and 30 d to assess wound contraction, persistency of the scaffold, integration rate and wound contamination. At day 30th the animals were euthanized and skin biopsies were taken for histopathological and histomorphometric analysis. Animals were housed in a certified animal facility under controlled standard conditions and a veterinarian carried out all the experiments. Clinical, histologlcal and histomorphometric data indicate that CS-GCs loaded with the A. vera extract does not integrate into full-thickness skin wounds and have a degradation rate significantly lower than the one of CS-GC unloaded, probably because an interaction between the extract and the scaffold increase their cross-linking.