Management of bioburden and tissue regeneration in diabetic wounds using engineered matrices - The goal of this Phase I SBIR proposal is to demonstrate the feasibility of an inherently broad-
spectrum antimicrobial tissue scaffolding matrix capable of eliminating infecting bacterial pathogens,
and improve wound closure in diabetics. Delayed non-healing diabetic wound is responsible for about
100,000 annual non-traumatic lower-limb amputations in the US. Microbial infections further complicate the
wound and it has been suggested that pathogenic biofilms play a major role in the prevention of wound
healing. The presence of biofilms and the emergence of multi drug resistant organisms (MDROs) have made
the current topical and systemic antibiotics becoming progressively less effective to combat diabetic wound
infections. While prevention and elimination of pathogens from a diabetic wound is crucial, it is equally
important to promote the wound closure by tissue regeneration to reduce the chance of further wound
infection.
Unfortunately, current products all show limited efficacy in these aspects. G4db, the proposed product
overcomes current limitations by both (i) preventing/eliminating infection through a unique mechanism of action
that is broad spectrum antibacterial, and (ii) promoting tissue regeneration by providing cell attachment sites
within the scaffolding matrix. Unlike any of the products currently used in the clinics, G4db does not rely on
using any externally added antibiotics, but rather takes advantage of charge composition to exert toxicity
against Gram-positive and -negative bacteria (including antibiotic resistant strains). Furthermore, G4db relies
only on sequences for antimicrobial charge ratio, and therefore is cell friendly, non-inflammatory and nontoxic
with a structure and pore size very similar to the native extracellular matrix (ECM).
To establish feasibility for the treatment of diabetic wound infections, we propose the following two main tasks:
Specific Aim 1) Therapeutic in vivo efficacy of G4db to eliminate infection. Demonstrate the in vivo
feasibility of G4db as an antimicrobial that prevents colonization of P. aeruginosa, a common pathogen
associated with wound infections.
Specific Aim 2) G4db tissue scaffolding matrix accelerates tissue regeneration. Demonstrate in vivo
efficacy of G4db as tissue scaffolding matrix that promotes tissue regeneration in full-thickness dorsal
excisional wounds in a diabetic swine model.
It is expected that the generated data will provide the necessary information to move the proposed product into
commercialization. In SBIR Phase II, we will validate the hydrogel in an infected wound healing swine model,
establish GMP manufacturing, and execute GLP studies in preparation for our FDA submission.
