Safety of Silk-elastin Sponges in Patients with Chronic Skin Ulcers: A Phase I/II, Single-center, Open-label, Single-arm Clinical Trial

Abstract

Background: Although traditional wound dressings such as collagen scaffolds promote granulation tissue formation, the efficacy of these dressings in chronic wounds is limited because of high susceptibility to bacterial growth. Biomaterials that can be applied to chronic wounds should have an anti-bacterial function. We previously reported that administering a silk-elastin solution that forms moisturizing hydrogels to wound surfaces of diabetic mice reduced bacterial growth and promoted granulation tissue formation compared with control or carboxymethyl cellulose hydrogels. We hypothesized that silk-elastin promotes wound healing in human chronic wounds by suppressing bacterial growth. Methods: An open-label, clinical case series was conducted with a prospective, single-arm design at Kyoto University Hospital in Kyoto, Japan. In this study, 6 patients with chronic skin ulcers of any origin (2 < ulcer area (cm2) < 25) on their lower extremities were included; patients with critical ischemia were excluded. Silk-elastin sponges were applied and covered with a polyurethane film without changing the dressing for 14 days. Inflammation triggered treatment discontinuation due to fear of infection. The primary study endpoint was adverse events, including inflammation and infection. Results: Poor hydrogel formation, possibly due to continuous exudation, was observed. No serious adverse events were noted. Two patients discontinued treatment on day 6 and day 7, respectively, due to inflammation, but they were not infected. The other 4 patients completed the 14-day silk-elastin sponge treatment without infection. Conclusion: Silk-elastin sponge is safe for chronic skin ulcers, and its ability to promote wound healing should be determined by confirmatory clinical trials.

Impact of silk hydrogel secondary structure on hydrogel formation, silk leaching and in vitro response

“…A small ongoing clinical trial (NCT04085822) sponsored by Silk Medical Aesthetics Inc (Medford, MA, USA) is examining the use of this technology to improve aesthetic and the results are eagerly awaited. Small-scale clinical trials using fibroin formulated as silk films 15 , sponges 16 and knitted scaffolds 17 , 18 have also shown favourable outcomes for both wound repair and aesthetics. This work is now being complemented by preclinical studies.…”

Clinical Utility of Silk-Elastin Sponge in Patients with Chronic and Acute Skin Ulcers: Study Protocol of a Multicenter Clinical Trial

“…The results of the previous clinical study of silk-elastin sponge revealed that poor hydrogel formation, possibly due to excessive exudate, caused unhealthy granulation tissue formation [ 12 ]. In this trial, to reduce the exudate and promote hydrogel formation, the investigator can use wound dressing that absorbs the exudate or apply the silk-elastin sponge on the next day of debridement.…”

“…This number is based on the results of previous clinical trials. In the previous study of silk-elastin sponge in patients with chronic wounds in the lower leg, 4 out of 6 patients (67%) showed the formation of a healthy wound bed at 5–16 days after the application of silk-elastin sponge [ 12 ]. For comparison, a clinical trial in Japan using a negative pressure wound therapy device (Renasys; Smith & Nephew) for chronic and acute wounds is a reasonable reference because the endpoints of the Renasys trial are similar to those of this silk-elastin sponge trial [ 18 ].…”

“…Silk-elastins are artificial proteins that were developed by genetic engineering and biological production methods using Escherichia coli [ 7 ]. Silk-elastins have a unique feature of temperature-mediated self-gelation [ 8 ], which has led to the development of biomaterials using silk-elastin: delivery systems for drugs and viruses [ 9 , 10 ], 3-dimensional tissue-engineering scaffolds [ 11 ], and wound healing materials [ 12 – 15 ]. We have previously shown with in vitro studies and animal models that SE-P47K, a type of silk-elastin, promotes wound healing [ 13 – 16 ].…”

“…On the basis of these results, a phase I/II clinical study was conducted, whose main objective was to confirm the safety and feasibility of silk-elastin sponge for treating patients with chronic ulcers [ 12 ]. That study was an open-label, single-center study with no control group.…”