Development of a Novel Material to Promote Wound Healing at Bronchial Defects.

BACKGROUND: Bronchopleural fistula (BPF) is a critical complication that may progress to pneumonia and empyema, but optimal treatment remains uncertain. Our purpose was to develop a novel material for bronchial occlusion that can be used to treat BPF by blocking airflow and promoting wound healing. METHODS: Sponges were prepared in concentrations of 25, 40, and 50 mg/dL of silk-elastin by hydrophobic processing. Five adult Beagle dogs underwent right anterior lobectomy, and 5 underwent left posterior lobectomy. Silk-elastin sponges were placed at bronchial stumps of 8 dogs, and silicone plugs were placed at the stumps of 2 dogs as a control. RESULTS: Postoperative complications were not observed, except in 1 dog in which the silicone plug had been placed and which had massive subcutaneous emphysema at 4 weeks after operation. Histologic examination revealed that stumps were covered with connective tissue and that there was more regeneration of airway epithelium in the silk-elastin sponge group than in the silicone plug group. There were increased numbers of myofibroblasts around the bronchial stump occluded by silk-elastin sponges at 2 weeks after placement, which completely disappeared after 2 months, during which abundant neovascularization occurred. CONCLUSIONS: We showed that silk-elastin sponges can manage and promote regeneration of bronchial epithelium. Our results demonstrate that bronchial occlusion with a silk-elastin sponge is a promising option for treatment of BPF.

The development of a novel wound healing material, silk-elastin sponge.

Silk-elastin is a recombinant protein polymer with repeating units of silk and elastin blocks. This novel wound healing promoting material has the ability to self-assemble from a liquid to a gel. We have already reported that an aqueous solution of silk-elastin has the potential to accelerate wound healing; however, there are several problems in applying silk-elastin in the clinical setting. To solve these problems, we developed a silk-elastin sponge that is easy to use in the clinical setting. In the present study, we examined whether the wound healing effect of the silk-elastin sponge is equal to the aqueous solution of silk-elastin in vivo. The granulation tissue formation promoting effect of the silk-elastin sponge was equal to that of the aqueous solution the silk-elastin, as after application to the wound surface, the sponge was absorbed and dissolved by the exudate. At body temperature the silk-elastin then formed temperature gel. The silk-elastin gel that was obtained contained abundant cytokines from the exudate. We believe that silk-elastin sponge can be applied to various wounds that are difficult to treat with the aqueous solution.

Effect of an artificial silk elastin-like protein on the migration and collagen production of mouse fibroblasts.

A silk elastin-like protein (SELP) is an artificial compound composing silk fibroin-like and elastin-like tandem repeats. The objective of this study is to evaluate the SELP effect on the migration, proliferation, and proteins production of L929 mouse fibroblasts. Upon culturing with different concentrations of SELP, the cells migration and their collagen production significantly enhanced in the SELP concentrations from 10(-3) to 10 µg/ml. However, irrespective of the SELP concentration, no difference in the production of fibronectin, basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and stromal cell-derived factor 1α (SDF-1α) was observed. When the migration of mouse peritoneal macrophages by SELP was evaluated, significant enhancement of macrophages migration was observed in any concentration. It is concluded that the SELP has a potential to promote the migration of fibroblasts and macrophages, and the fibroblast collagen production.

Effect of ProNectin F derivatives on cell attachment and proliferation.

ProNectin F (PnF) was chemically modified by introducing some functional groups to prepare various derivatives of primary amino (PnF-N1), tertiary amino (PnF-N3), quaternary ammonium (PnF-N4), carboxyl (PnF-COOH) and sulfonyl groups (PnF-SO3H). When C3H10T1/2 cells were cultured on non-treated dishes coated with the derivatives, the number of mesenchymal cells attached to the culture dishes increased for the coating with PnF-COOH and PnF-SO3H, even at their low adsorption amount. The cytotoxicity was high for the coating of PnF-N1 and PnF-N4 compared with that of the PnF-N3, PnF-COOH and PnF-SO3H. The treatment with integrin α5 and αV antibodies suppressed the cell attachment to the dishes coated with PnF-COOH and PnF-SO3H. The phosphorylation of extracellular signal-regulated kinase (ERK) was upregulated for cells attached to the dishes coated with PnF-COOH and PnF-SO3H, indicating their enhanced proliferation. It is concluded that the chemical derivatization of PnF enhanced the ability of cell attachment and proliferation.