Drug-Induced Regeneration and Re-Innervation in a Mouse Digit Amputation Model
Abstract
In the proposed studies, we are attempting to leverage our experience in soft and hard tissue regeneration induced by the HIF1 alpha-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) the role of peripheral re-innervation in rat forelimbs on injury restoration, and 3) optimization of drug potency and delivery in these systems. Our progress during this first year includes studies on surgically amputated digits in mice using Micro-CT analysis and immunohistochemistry showing changes with drug therapy as early as day 7. Significant changes at the digit cut site and formation of a boney callus are observed. Optimal drug dosing experiments for the rat forelimb nerve repair experiments were accomplished. 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 both earlier and later time points post digit amputation, begin extensive 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, 2020
- Accession Number
- AD1115967
Entities
People
- Phillip B. Messersmith
Organizations
- University of California