Wound healing and tissue engineering
Inventors
Frank, Markus H. • Frank, Natasha Y. • Orgill, Dennis P. • Murphy, George F.
Assignees
Brigham and Womens Hospital Inc • Boston Childrens Hospital • US Department of Veterans Affairs
Publication Number
US-11446331-B2
Publication Date
2022-09-20
Expiration Date
2034-05-09
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Abstract
The present invention is directed to wound healing scaffolds cografted with a population of stem cells, wherein the population of stem cells are ABCB5+ stem cells. The scaffolds are, for instance, collagen glycosaminoglycan scaffolds.
Core Innovation
The invention is directed to wound healing scaffolds cografted with a population of stem cells, wherein the population comprises ABCB5+ stem cells. These scaffolds are exemplified by collagen glycosaminoglycan scaffolds such as INTEGRA® Meshed Bilayer Wound Matrix. The ABCB5+ stem cells demonstrate multipotent differentiation plasticity and enhance wound healing and tissue regeneration when employed alone or within biodegradable scaffolds.
The problem addressed arises from the high prevalence of chronic wounds in the United States, exceeding one million cases annually, leading to significant treatment costs. These wounds compromise the protective barrier function of tissues, resulting in fluid loss, infection vulnerability, metabolic imbalances, and potentially serious outcomes such as limb amputation. Current methods focus on drainage, infection prevention, inflammation reduction, and minimizing tissue and fluid loss but face challenges in restoring normal tissue function and structure.
Adult stem cells have the potential for plasticity that may replicate fetal scarless regenerative healing. The invention leverages ABCB5 expression as a marker to isolate stem cells capable of supporting regenerative wound healing and tissue engineering. The scaffold serves as a supporting structure facilitating cell infiltration and new tissue synthesis, promoting not only wound closure but also tissue regeneration with potential for reduced scarring and restoration of cutaneous structures.
Claims Coverage
The patent contains one independent claim describing a method for tissue engineering utilizing a specific scaffold and cell composition. The claim covers the scaffold properties, stem cell purity, and procedural aspects.
Biological tissue scaffold composition and structure
The scaffold is a porous matrix of cross-linked collagen and glycosaminoglycan incorporating a separate semi-permeable layer, enhancing biocompatibility and functionality for tissue engineering applications.
High purity of ABCB5(+) stem cells
At least 99% of the total cells present in the scaffold are ABCB5(+) stem cells, ensuring a substantially pure population critical for promoting tissue formation.
Exclusion of ex-vivo cytokine treatment prior to implantation
The ABCB5(+) stem cells used are not treated with soluble cytokines ex-vivo or in vitro prior to implantation, preserving their native characteristics for effective tissue engineering.
The independent claim encompasses a method of tissue engineering using a collagen glycosaminoglycan scaffold with a semi-permeable layer, seeded predominantly with ABCB5(+) stem cells that are not pre-treated with soluble cytokines. The inventive features emphasize scaffold composition, stem cell purity, and procedural steps preserving stem cell properties for effective tissue regeneration.
Stated Advantages
Enhanced wound healing and tissue regeneration through the use of scaffolds cografted with ABCB5+ stem cells.
Ability to isolate multipotent ABCB5+ stem cells with superior differentiation plasticity compared to previously available markers.
Reduced inflammatory stroma thickness and accelerated wound closure demonstrated in animal models with ABCB5+ stem cell deployment.
Facilitation of scarless or reduced-scar tissue regeneration as opposed to traditional scar formation.
Compatibility with commercially approved scaffolds such as INTEGRA®, enabling clinical translation.
Documented Applications
Treatment of various types of wounds including partial and full-thickness wounds, pressure ulcers, venous ulcers, diabetic ulcers, chronic vascular ulcers, tunneled/undermined wounds, surgical wounds, trauma wounds, and draining wounds.
Tissue engineering by seeding collagen glycosaminoglycan scaffolds with ABCB5+ stem cells to promote formation or regeneration of tissue defects.
Use in regenerative wound healing in skin and ocular tissues, including burns, diabetic ulcers, and ocular conditions such as corneal epithelial wounds.
Treatment of connective tissue damage including bone, cartilage, tendon, ligament, muscle, and adipose tissue regeneration.
Applications in regenerative therapies for liver disease, neurodegenerative disorders, kidney disease, corneal tissue repair, and lung tissue regeneration.
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