Análise in vivo da biocompatibilidade e biodegradação de biocompósitos de gelatina e hidroxiapatita de tilápia do nilo (Oreochromis niloticus)

Abstract

The Brazilian fish farming industry generates by-products on a large scale that allow the extraction of collagen and hydroxyapatite. The natural origin awakens biotechnological interest in the development of implantable medical and dental devices for bone regeneration. This utility model is still unexplored for the fish source. The objective of this research was to analyze the biocompatibility and biodegradation of biocomposites extracted from Nile tilapia (Oreochromis niloticus). Skin and scales of tilapia from Fortaleza-CE allowed the extraction of hydroxyapatite and collagen gelatin. Biocomposites with different concentrations of gelatin (G), hydroxyapatite (HAp) were formulated, cross-linked with riboflavine and lyophilized: 60%G:40% HA (G1), 70%G:30% HA (G2) and 80%G:20%HA (G3). After validation by physical-chemical tests, the materials followed for pre-clinical biological tests. In vivo analysis used 30 adult males Swiss mices, 15 of whom submitted to subcutaneous grafting with G1, G2 and G3 and another 15 with commercial collagen membrane (C +) or surgery without graft (C–). Necropsies of subcutaneous tissues at 1, 3 and 9 weeks were processed and embedded in paraffin. Histological sections allowed semi-quantitative analysis by scores of inflammatory criteria (neutrophils, lymphocytes, macrophages, multinucleated giant cells) and repair (neovascularization, connective tissue) according to ISO 10993-6, allowing the definition of the biocompatibility scale of each material. Statistical analysis of nonparametric data was performed using the Kruskal-Wallis test and Dunn's post-test, with p <0.05. As a result, G1 was mildly irritating up until 9 weeks, while G2 and G3 were mildly irritating up to 3 weeks and non-irritating up to 9 weeks, similar to C +. Between 1 and 9 weeks, there was a decrease about: inflammatory criteria, despite the persistence of giant cells in 9 weeks being bigger in G3 followed by G1 and G2 against C + and C–; neovascularization; and material integrity, with a bigger presence of G1 than G3 against C– and less presence of G2 against C +. During this period, there was only a constant increase in connective tissue, more abundant in 9 weeks in G1 compared to C + and C– and G2 for C +. Although all tilapia materials have been biocompatible and partially biodegradable, G1 suggests greater potential for use as a membrane barrier in clinical procedures, with their biological performance associated with greater mineral concentration compared to the organic phase in the biocomposite.