Methods and compositions for wound healing
Inventors
McAnulty, Jonathan F. • Murphy, Christopher • Abbott, Nicholas
Assignees
Publication Number
US-8709393-B2
Publication Date
2014-04-29
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 polymers 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 invention provides novel methods and compositions for promoting and enhancing wound healing by altering the intrinsic chemical composition and/or physical attributes of the wound bed. This includes the use of cross-linker covalent modification molecules to attach and deliver wound active agents directly to a wound, and the formation of polyelectrolyte layers on the wound surface using oppositely charged polymers. Furthermore, it describes incorporation of wound active agents into such polyelectrolyte layers, nanoparticles, or microparticles for localized delivery to wounds.
The problem being addressed is the impaired healing of wounds due to dysregulation of the wound healing process, which involves six major components including inflammation, fibroblast proliferation, vascular proliferation, connective tissue synthesis, epithelialization, and wound contraction. Chronic wounds, especially in diabetic individuals and others with systemic diseases, present a significant health burden and fail to respond adequately to conventional treatments such as standard wound dressings and pharmaceutical agents. Current therapies do not adequately modify the intrinsic chemistry or structure of the wound bed, which contributes to wound persistence and poor healing.
The invention offers solutions by engineering the wound bed environment through chemical and physical modifications to provide a uniform and functionalized surface that facilitates controlled immobilization and delivery of therapeutic agents. This comprehensive approach allows for tailored modulation of cellular behaviors critical to wound healing, enabling personalized treatment strategies to enhance healing outcomes across diverse wound types and patient populations.
Claims Coverage
The patent includes one independent claim which outlines a method of treatment involving covalent modification of a wound bed and delivery of therapeutic agents.
Method for covalently modifying wound beds presenting amine and sulfhydryl groups
A method comprising providing a subject with a wound bed presenting amine and sulfhydryl groups, applying a bifunctional covalent modification agent that reacts with amine and sulfhydryl groups to covalently modify the wound bed.
Covalent binding of wound active agents to modified wound bed
Contacting the covalently modified wound bed with at least one wound active agent such that the active agent covalently binds to the bifunctional covalent modification agent incorporated in the wound bed, enhancing wound healing.
Incorporation of wound active agent gradients
Applying the wound active agent to the covalently modified wound bed so as to form a concentration gradient over the wound surface.
Methods of applying bifunctional covalent modification agents
Applying the bifunctional covalent modification agent to the wound bed using methods such as stamping, spraying, pumping, painting, smearing, or printing.
Bifunctional covalent modification agents incorporating alkyne groups
Use of bifunctional covalent modification agents that comprise an alkyne group to facilitate functionalization and subsequent agent attachment via click chemistry.
The claims cover a comprehensive method for enhancing wound healing by chemically modifying the wound bed with bifunctional covalent agents reactive toward specific functional groups in the wound, followed by covalent incorporation of therapeutically active agents, with various modes of application and chemical functionalities facilitating versatile treatment.
Stated Advantages
The invention offers safe, effective, and interactive means for enhancing the healing of chronic and severe wounds.
It provides a tailored therapeutic approach adaptable to various wound types and patient populations.
Modification of wound bed chemistry and structure reduces the amount of active agent needed for effective healing.
The methods allow for controlled delivery and formation of gradients of active agents within the wound bed.
The approach enables modulation of cellular properties to foster desirable wound healing responses, including vascularization, fibrosis, and epithelial coverage.
Documented Applications
Treatment of chronic, severe, and pathologic wounds including diabetic ulcers, venous stasis ulcers, pressure sores, and burn wounds.
Enhancement of wound healing by covalent attachment and delivery of therapeutic agents such as trophic factors, extracellular matrix components, antimicrobial compounds, enzymes, and siRNAs.
Use in wound care for both external and internal tissues damaged by various causes such as trauma, chemical burns, and disease.
Modulation of wound bed physical properties such as compliance, charge, and topography to influence cell behavior and accelerate healing.
Personalized treatment protocols tailored to individual patient wound characteristics and healing needs.
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