Development and Preclinical Evaluation of Acellular Collagen Scaffolding and Autologous Artificial Connective Tissue in the Regeneration of Oral Mucosa Wounds

Abstract

This work assessed wound healing response in rabbit oral lesions grafted with autologous artificial connective tissue or acellular collagen scaffolds. Autologous artificial oral connective tissue (AACT) was produced using rabbit fibroblasts and collagen I scaffolds. Before implantation, AACT grafts were assayed to demonstrate the presence of fibroblasts and extracellular matrix components, as well as the expression of characteristic genes and secretion of chemokines, cytokines, and growth factors. AACT grafts were tested in the rabbits from which the fibroblasts were obtained, whereas acellular collagen type I scaffolds (CS) were evaluated in a separate group of rabbits. In both cases, contralateral wounds closed by secondary intention were used as controls. In a separate experiment, AACT-grafted wounds were directly compared with contralateral CS-grafted wounds in the same animals. Wound contraction and histological parameters were examined to evaluate closure differences between the treatments in the three animal experiments performed. Contraction of wounds grafted with AACT and CS was significantly lower than in their controls (p < 0.05). Additionally, AACT significantly lowered wound contraction when compared with CS (p < 0.05). Intriguingly, it was observed that AACT-grafted wounds initially displayed a significantly higher (p < 0.05)-albeit transient-inflammatory response than seen in CS-grafted wounds and secondary healed wounds. This suggests that an early inflammatory component may contribute to tissue regeneration. Altogether, the results suggest that AACT- and CS-grafted wounds favor regeneration of oral mucosa.

Collagen-Gelatin Scaffold Impregnated with bFGF Accelerates Palatal Wound Healing of Palatal Mucosa in Dogs

“…It has been reported that wound contraction occurred during the first weeks after wounding [3,19]. It was also reported that promoted neovascularization in the initial 7 d after implantation accelerated the formation of granulation tissue [20].…”

“…It is very difficult to obtain enough oral mucosa to cover large defects during palatoplasty and the raw surface of exposed palatal bone heals by secondary intention, resulting in wound contraction with subsequent scar tissue formation [1,2]. The scar tissue adversely affects the growth of the maxillofacial complex during development [3][4][5].…”

“…It has been reported that collagen scaffolds implanted in oral mucoperiosteal defects improve wound healing and reduce contracture and scar tissue formation [3,[14][15][16]. Recently we succeeded in developing a novel scaffold that can provide sustained release of bFGF [17].…”

Comparative evaluation of healing biomarkers in skin wound exudates using a nanobiosensor and histological analysis of full‐thickness skin wounds grafted with multidirectional or unidirectional artificial dermis

“…Mouse monoclonal antihuman epidermal growth factor (anti‐EGF), rabbit polyclonal antihuman angiopoietin 2 (anti‐Ang‐2), and mouse monoclonal antihuman transforming growth factor‐β1 (anti‐TGF‐β1) were provided by Abcam (Cambridge, UK). The abovementioned human antibodies were used because previous work from others and us has found that human monoclonal and polyclonal antibodies cross‐react with their rabbit counterparts (Bustos et al, ; Espinosa, Sosnik, & Fontanilla, ; Popkov et al, ; Ying et al, ).…”

“…Collagen type I scaffolds with multidirectional and unidirectional pore orientation were prepared following reported methodology (Bustos et al, ; Espinosa et al, ; Suesca et al, ). Briefly, the collagen dispersion (5 mg/ml) was poured, frozen (−20°C), and lyophilized (Virtis, SP Industries, USA) to obtain multidirectional scaffolds.…”