Extended release of bioactive factors to treat refractory wounds Chronic wounds significantly decrease quality of life, lead to severe disability, and are huge burdens on healthcare and caregivers. Diabetes mellitus is expected to afflict 366 million people worldwide by 2030. Among these patients, approximately 15% will develop diabetic foot ulcers. Underlying chronic wounds, abnormal cell phenotypes and chronic inflammation inhibit normal healing processes and elevate the risk of infection. Current clinical solutions are expensive, time-consuming, largely unsuccessful, and lack patient self-management. The overarching goal of this translational study is to advance nursing science and the wound care field, by healing chronic wounds with one-time administration of sustained, local release of growth factors. This effective and economical treatment will be achieved using a new vehicle that protects the bioactivity of the protein cargo. Growth factor signaling plays a pivotal role in the natural wound healing process. The major limitation in growth factor therapies has been the lack of an appropriate delivery system to provide for prolonged signaling. Controlled delivery of growth factor will reduce patient morbidity and risk of infection in chronic wounds while helping patients to manage their care more autonomously. This research focuses on testing the efficacy of a delivery system we recently designed for wound-implicated growth factors and has three specific aims:
Aim 1. Investigate the effects of HB-EGF coacervate on wound healing in vitro using normal and diabetic primary human dermal cells and evaluate the safety of the coacervate treatment.
Aim 2. Evaluate the efficacy of controlled delivery of HB-EGF to improve diabetic wound healing in a polygenic type 2 diabetic mouse model.
Aim 3. Investigate the controlled delivery of HB-EGF to accelerate diabetic wound healing in a porcine model. This proposal will provide the foundation for an easy-to-use product that significantly improve healing of wounds, increase patient self-reliance and quality of life, and reduce the interruption and loss of productivity patients currently must accept. Therefore, this new technology would enable not only improved health outcomes, but also more self-management for individuals with chronic wounds.

Public Health Relevance

Chronic wounds significantly decrease life quality, lead to severe disability, and are huge burdens on healthcare and caregivers. The goal of this research is to create a prototype bioactive tape that can control the release of growth factors in order to accelerate closure of chronic wounds. Successful completion of the proposed research will pave the way for growth factor therapy for chronic wound healing in humans, reduce healthcare cost, and improve the quality of life for patients with chronic wounds.

Agency
National Institute of Health (NIH)
Institute
National Institute of Nursing Research (NINR)
Type
Research Project (R01)
Project #
5R01NR016436-04
Application #
9653211
Study Section
Nursing and Related Clinical Sciences Study Section (NRCS)
Program Officer
Hamlet, Michelle R
Project Start
2016-07-22
Project End
2021-04-30
Budget Start
2019-05-01
Budget End
2020-04-30
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Cornell University
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Hwang, Mintai P; Ding, Xiaochu; Gao, Jin et al. (2018) A biocompatible betaine-functionalized polycation for coacervation. Soft Matter 14:387-395
Awada, H K; Long, D W; Wang, Z et al. (2017) A single injection of protein-loaded coacervate-gel significantly improves cardiac function post infarction. Biomaterials 125:65-80
Ding, Xiaochu; Wang, Yadong (2017) Weak Bond-Based Injectable and Stimuli Responsive Hydrogels for Biomedical Applications. J Mater Chem B 5:887-906
Long, Daniel W; Johnson, Noah R; Jeffries, Eric M et al. (2017) Controlled delivery of platelet-derived proteins enhances porcine wound healing. J Control Release 253:73-81
Johnson, Noah R; Wang, Yadong (2015) Drug delivery systems for wound healing. Curr Pharm Biotechnol 16:621-9