Interferon-γ-loaded collagen scaffolds reduce myofibroblast numbers in rat palatal mucosa.

Wound contraction and scar formation after cleft palate repair lead to growth impairment of the maxilla and midface. Myofibroblasts play a key role in these processes. The application of an interferon-γ (IFN-γ)-loaded collagen scaffold after surgery might reduce the differentiation of myofibroblasts. In this study, the tissue response to IFN-γ-loaded collagen scaffolds was evaluated after implantation in the palate of rats. Scaffolds, with or without IFN-γ, were implanted submucoperiosteally in the palate of two groups of 25 five-week-old male Wistar rats. Groups of five rats were sacrificed at 1, 2, 4, 8, and 16 weeks post-implantation and processed for histological analyses. On haematoxylin and eosin-stained sections, the cell density and number of giant cells within the scaffolds were determined. Blood vessels, inflammatory cells, and myofibroblasts were detected by immunohistochemistry. The data for cell density, blood vessels, and giant cells were compared with a two-way analysis of variance. The scores for myofibroblasts and inflammation were compared by a rank sum test. A mild and rapidly subsiding inflammatory and foreign body response was found in both groups. Angiogenesis had already begun after 1 week, showed a peak after 4 weeks, and declined thereafter. IFN-γ induced a faster influx of host cells and a major reduction in myofibroblast numbers. The scaffolds might be suitable for future applications in oral surgery.

FGF-2-loaded collagen scaffolds attract cells and blood vessels in rat oral mucosa.

BACKGROUND: Wound contraction and scar formation after cleft palate repair impair the growth of the maxilla. The implantation of a growth factor-loaded scaffold might solve these problems. METHODS: The tissue response to fibroblast growth factor (FGF)-2 loaded collagen scaffolds was evaluated after implantation in the palate of rats. Scaffolds, with and without FGF-2, were implanted submucoperiosteally in the palate of 25 rats and evaluated after up to 16 weeks. On hematoxylin and eosin (H&E)-stained sections, the cell density and the number of giant cells within the scaffolds were quantified. Infiltration of inflammatory cells, myofibroblasts, and the number of blood vessels were quantified after immunohistochemistry. RESULTS: The cell density was significantly higher in the FGF-2 group up to 4 weeks after implantation (102% at 2 weeks, P < 0.001). The number of blood vessels was also significantly higher in the FGF-2 group at 1 and 2 weeks (316% at 1 week, P = 0.003), but the myofibroblast score was lower (100% at 2 weeks, P = 0.008). A comparable mild and rapidly subsiding inflammatory response and foreign body reaction were found in both groups. CONCLUSION: FGF-2-loaded scaffolds displayed a faster influx of host cells, an increased rate of vascularization, and a reduced differentiation of myofibroblasts. These scaffolds might therefore be highly suitable for intra-oral reconstructions, such as cleft palate repair.

Tissue reactions to collagen scaffolds in the oral mucosa and skin of rats: environmental and mechanical factors.

OBJECTIVE: To compare the tissue reactions to implanted collagen scaffolds in the palate and the skin of rats. DESIGN: Crosslinked collagen scaffolds were implanted submucoperiosteally in the palate, and subcutaneously on the skull and on the back of 25 rats and evaluated after up to 16 weeks. On H&E-stained sections, the cell density and the number of giant cells within the scaffolds were determined. Blood vessels, inflammatory cells, and myofibroblasts were detected by immunohistochemistry. RESULTS: A faster ingrowth of myofibroblasts and blood vessels in the palate was found during the first week compared with the skin. A more severe inflammatory response was initially found in the back skin. Furthermore, about twice as much giant cells were present in these scaffolds. CONCLUSION: The oral environment seems to promote the ingrowth of myofibroblasts and blood vessels into the scaffolds. Mechanical stimuli seem to enhance the initial inflammatory response. Overall, the scaffolds were gradually integrated within the host tissue, eliciting only a transient inflammatory response. The scaffolds were biocompatible and are promising for future applications in oral surgery.

Collagen scaffolds implanted in the palatal mucosa.

Scar formation after repair of the cleft palate leads to growth impairment of the upper jaw and midface. The implantation of a suitable scaffold during surgery may reduce this adverse effect. However, little is known about tissue reactions to scaffolds implanted in the oral cavity. Our goal was to analyze the tissue reactions to cross-linked type I collagen scaffolds after submucoperiosteal implantation in the palate of rats. Collagen type I scaffolds were implanted in the palate of 25 male Wistar rats. Groups of 5 rats were killed consecutively after 1, 2, 4, 8, and 16 weeks and were processed for histologic and immunohistochemical analyses. After 1 and 2 weeks, 3 rats from the sham group were also killed. On hematoxylin and eosin-stained sections, the cell density and the number of giant cells were determined. Blood vessels, inflammation, and the presence of myofibroblasts were detected by immunohistochemistry. An influx of inflammatory cells started after 1 week but had completely subsided after 8 weeks. Myofibroblasts were observed within the scaffolds only in the first 2 weeks. Angiogenesis already started after 1 week and showed a peak after 4 weeks, slowly declining afterward. The scaffolds were gradually integrated within the host tissue and only elicited a mild and transient inflammatory response. The scaffolds were biocompatible and seemed to be promising for future applications in cleft palate surgery.