Drug-Induced Regeneration and Re-Innervation in a Mouse Digit Amputation Model
Abstract
In the proposed studies, we have leveraged our experience in soft and hard tissue regeneration induced by the HIF1alpha-stabilizing drug, 1,4-DPCA, in a drug delivery system (PEG-DPCA nanogel) towards therapies for hand and nerve injuries and digit regeneration. Here, we are exploring the effect of this drug on 1) digit regrowth post-amputation and nerve growth, 2) drug effects on peripheral re-innervation in rat forelimbs after injury and 3) optimization of drug potency and delivery in these systems. Our progress during this second year includes studies on surgically amputated digits in mice using Micro-CT analysis and immunohistochemistry showing changes with drug therapy at 6 months. Significant changes at 6 months showing bone remodeling at the digit cut site and possible formation of a joint structure are observed. One model of rat forelimb nerve resection showed that drug enhanced grip strength, reduced muscle atrophy, and nerve fiber regrowth. A second model was inhibited by drug suggesting a toxic effect and need for reduced amounts of drug. Finally, we made progress in developing a new carrier system for 1,4-DPCA, making it more potent and easier to deliver. During this coming year, we will explore multiple drug injections, new dosing, and effects of BMP addition post digit amputation, continue studies in forelimb nerve regrowth and effects on digit function, and further develop the 1,4-DPCA drug delivery system and modification of 1,4-DPCA compounds.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2021
- Accession Number
- AD1146802
Entities
People
- Ellen S. Heber-katz
Organizations
- Lankenau Institute for Medical Research