# Development of Silk Fibroin Grafts for Reconstruction of Esophageal Defects

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $342,805

## Abstract

PROJECT SUMMARY/ABSTRACT
 Loss of esophageal tissue from congenital and acquired abnormalities is often surgically managed with
autologous gastrointestinal interposition grafts in order to restore organ continuity. Unfortunately, these
approaches are associated with severe adverse complications such as esophageal dysmotility, dysphagia, and
donor site morbidity. Silk fibroin (SF) biomaterials provide an exceptional combination of physical characteristics
including high tensile strength and elasticity, diverse processing flexibility, and tunable degradability that are well
suited to support esophageal function. Therefore, these scaffolds may overcome the deleterious side-effects
associated with conventional reconstructive techniques and serve as “off-the-shelf” grafts for esophageal tissue
repair. By understanding the role of the innate immune response in facilitating constructive remodeling of
esophageal defects, we will design SF implants with selective microenvironmental cues sufficient to modulate
macrophage activation phenotypes toward maximal regenerative outcomes. In this proposal, we will test the
overall hypothesis that: acellular SF matrices promote functional restoration of esophageal defects via CD206+
M2a macrophage-dependent constructive remodeling. The specific aims of the application are: Specific Aim
1: Develop SF grafts for functional repair of long-gap esophageal defects in a preclinical animal model. Specific
Aim 2: Determine the impact of CD206+ M2a macrophages on scaffold mediated, constructive remodeling of
esophageal defects. Specific Aim 3: Determine the efficacy of immunomodulatory SF grafts to maximize
constructive remodeling and restore organ function in esophageal stricture disease.

## Key facts

- **NIH application ID:** 9957091
- **Project number:** 5R01DK107568-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Carlos R Estrada
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $342,805
- **Award type:** 5
- **Project period:** 2019-10-12 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9957091

## Citation

> US National Institutes of Health, RePORTER application 9957091, Development of Silk Fibroin Grafts for Reconstruction of Esophageal Defects (5R01DK107568-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9957091. Licensed CC0.

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