Methods and compositions for wound healing
Inventors
Abbott, Nicholas L. • Agarwal, Ankit • Murphy, Christopher J. • McAnulty, Jonathan F.
Assignees
Publication Number
US-9174839-B2
Publication Date
2015-11-03
Expiration Date
2029-01-30
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Abstract
The present invention relates to methods and compositions for wound healing. In particular, the present invention relates to promoting and enhancing wound healing by utilizing cross-linker covalent modification molecules to attach and deliver wound active agents to a wound. In addition, the present invention provides methods and compositions utilizing oppositely charged polyelectrolytes to form a polyelectrolyte layer on a wound surface. The invention further relates to incorporating wound active agents into a polyelectrolyte layer for delivery to a wound.
Core Innovation
The present invention relates to methods and compositions for the modulation of wound healing by changing the intrinsic chemical composition and/or physical attributes of the wound bed. The invention provides formulations that alter physical attributes such as compliance, topography, and charge, and use cross-linker covalent modification molecules to attach and deliver antimicrobial compounds, extracellular matrices, scaffolds, and cytoactive agents to a wound. It also involves use of oppositely charged polyelectrolytes to form polyelectrolyte layers on wound surfaces, with incorporation of wound active agents into these layers for delivery.
The invention further contemplates the incorporation of non-charged polymers, nanoparticles, and microparticles into the wound bed through interactions including hydrogen bonding, to engineer the physical characteristics and chemical composition of the wound bed. Formulations promoting favorable and stable pH, surface charge, surface energy, osmotic environment, and balance of enzyme activity are also provided. This approach supports selective toxicity by delivering wound active agents like silver nanoparticles that are bactericidal but support mammalian cell growth.
The problem being solved arises from challenges in wound healing, especially chronic and pathologic wounds such as diabetic ulcers, pressure sores, and venous stasis ulcers. These wounds exhibit dysregulated healing processes due to altered wound bed chemistry and physical structure, systemic diseases, infections, and other factors. Existing treatments, including conventional dressings, pharmaceutical agents, and silver compounds, fail to adequately promote healing, suffer from toxicity, rapid inactivation, and poor residual activity. The invention addresses the need for safe, effective, interactive, and customizable means to modulate the wound environment and enhance healing by targeting the wound bed chemistry and structure directly.
Claims Coverage
The patent includes two independent claims covering an article and a kit related to wound healing applications.
Polyelectrolyte multilayer with releasable antimicrobial silver composition
An article comprising a polyelectrolyte multilayer formed from anionic and cationic polymers, 1 to 500 nm thick, disposed on a support selected from wound dressing and biologic wound dressing, having incorporated a releasable antimicrobial silver composition that releases 0.05 to 0.5 μg/cm2 of silver per day.
Kit including the polyelectrolyte multilayer article
A kit comprising the article described above, optionally packaged in a sterile package for wound treatment.
The independent claims focus on articles comprising nanoscale polyelectrolyte multilayers loaded with antimicrobial silver compositions for controlled silver release and kits containing such articles, emphasizing integration with wound dressings or biologic wound dressings to provide effective wound treatment with controlled antimicrobial activity.
Stated Advantages
Localized delivery of bactericidal silver reduces the amount of silver needed, thereby minimizing toxicity and discoloration of wounds.
Prolonged residual activity reduces the frequency of dressing changes, easing logistical burden in clinical settings.
Polyelectrolyte multilayers permit controlled spatial and temporal delivery of wound active agents, allowing for gradients and tailored wound healing responses.
Compositions support high bacterial killing efficiency while permitting growth and viability of mammalian cells such as keratinocytes and fibroblasts.
The invention enables engineering of the wound bed's physical and chemical properties to promote favorable cellular behaviors tailored to individual wound and patient characteristics.
Documented Applications
Treatment and enhancement of healing for chronic and acute wounds including diabetic ulcers, pressure sores, venous stasis ulcers, burn wounds, neuropathic ulcers, and surgical wounds.
Delivery of antimicrobial agents and growth factors to wounds via polyelectrolyte multilayers, nanoparticles, microparticles, and functionalized beads applied directly to wound beds.
Modification and functionalization of wound dressings and biologic wound dressings with antimicrobial and wound active agent-containing polymer multilayers.
Coatings on medical devices, including implantable and surface-contacting devices, to prevent infection and promote wound healing.
Use of polymer multilayers and particle-containing layers for modulating wound bed compliance, topography, charge, and enzyme activity to promote healing.
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