Decellularized composite tissue bioscaffolds for musculoskeletal tissue interface reconstruction and methods of production
Inventors
Chang, James • Woon, Colin • Pham, Hung
Assignees
US Department of Veterans Affairs • Leland Stanford Junior University
Publication Number
US-9782248-B2
Publication Date
2017-10-10
Expiration Date
2032-12-07
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Abstract
One aspect of the present invention is a method of producing a decellularized composite tissue bioscaffold for musculoskeletal tissue interface reconstruction by physicochemically treating a musculoskeletal tissue interface isolated from allogeneic sources. In certain embodiments, such musculoskeletal tissue interfaces can also be isolated from xenogeneic sources. The method comprises treatment of the interface with detergents, chemical oxidants and ultrasonic energy, and wash steps in between to remove residual detergents as well as oxidants. The resulting bioscaffold may be freeze-dried or lyophilized, sterilized and aseptically packaged for subsequent use.
Core Innovation
The invention provides a method for producing decellularized composite tissue bioscaffolds designed for musculoskeletal tissue interface reconstruction. This method involves physicochemical treatment of musculoskeletal tissue interfaces isolated from allogeneic or xenogeneic sources. Treatment includes application of detergents, chemical oxidants, and targeted ultrasonication to remove cellular components while maintaining the native biomechanical integrity of the tissues and their interfaces. This process also involves wash steps to remove residual chemicals and can culminate in freeze-drying, sterilization, and aseptic packaging for clinical use.
The core problem addressed concerns the difficulty and inadequacy of current surgical techniques in reconstructing musculoskeletal interfaces, particularly the transition zones between dissimilar tissues such as tendon or ligament to bone, which differ significantly in elastic modulus. Native allogeneic grafts provoke strong immune responses leading to graft rejection or failure, and autografts are limited by donor site morbidity and availability. The invention seeks to produce composite tissue bioscaffolds that are effectively decellularized to minimize immunogenicity, retain biomechanical properties, and facilitate improved healing with bone-to-bone and tendon-to-tendon integration in clinical grafting.
The invention also contemplates seeding the decellularized composite bioscaffolds with recipient-derived cells to enhance healing post-implantation. Various types of natural soft tissue-hard tissue interfaces such as tendon-bone, ligament-bone, muscle-bone, and cartilage-bone are included as bioscaffold sources. The bioscaffolds prepared by this method are particularly useful for reconstructing musculoskeletal injuries in upper and lower extremities, including treatment of anterior cruciate ligament tears, rotator cuff tears, Achilles tendon ruptures, meniscal injuries, and degenerative joint disorders.
Claims Coverage
The patent contains two independent claims addressing both a method of producing composite tissue bioscaffolds and the composite tissue bioscaffold product itself. Four main inventive features are identified from these claims.
Targeted ultrasonication for decellularization
The method involves subjecting only the soft-hard tissue interface of harvested composite tissue to targeted ultrasonication, effectively removing at least 90% of cells while retaining native biomechanical integrity.
Combined use of detergents and chemical oxidants
Following targeted ultrasonication, the composite tissue comprising soft tissue, hard tissue, and interface is contacted with detergents and chemical oxidants to remove extracellular matrix materials and further aid decellularization.
Composite tissue bioscaffold comprising soft tissue, hard tissue, and interface
The bioscaffold product includes a soft tissue, hard tissue, and soft-hard tissue interface obtained from mammalian cadavers and produced by the claimed physicochemical method to ensure host compatibility and preservation of biomechanical integrity.
Preparation and conditioning of bioscaffold for clinical use
The bioscaffold is optionally sterile, freeze-dried, aseptically packaged, and may be pre-seeded with cells harvested from the graft recipient to improve healing prior to implantation into various anatomical sites including upper and lower extremities, joints, pelvic floor, or muscle reinforcement.
The claims cover a method of producing a decellularized composite tissue bioscaffold using targeted ultrasonication combined with chemical treatments to remove cells while preserving biomechanical properties, and the resulting bioscaffold product designed for surgical implantation with improved host compatibility and mechanical function.
Stated Advantages
Minimized immunogenicity of the graft through substantial removal of cellular components, reducing host immune response and risk of graft rejection.
Preservation of native biomechanical properties of the composite tissue interface, allowing early mobilization and improved functional healing with bone-to-bone and tendon-to-tendon integration.
Provision of readily available, effective, and safe allogeneic and xenogeneic composite tissue bioscaffolds that overcome the limitations of autograft availability and donor site morbidity.
Capability to seed bioscaffolds with recipient cells prior to implantation, potentially accelerating healing and cellular integration.
Documented Applications
Surgical reconstruction of musculoskeletal tissue interfaces in the upper and lower extremities, including treatment of tendon and ligament injuries such as anterior cruciate ligament tears, rotator cuff tears, and Achilles tendon ruptures.
Reconstruction of dorsal scapholunate ligament tears using bone-ligament-bone composite grafts fashioned from proximal interphalangeal joint collateral ligaments.
Orthotopic reimplantation of composite tendon-bone grafts for complex tendon-bone losses involving long tendon segments, composite tissue loss, or insertional loss.
Use in meniscal injuries and degenerative joint disorders including arthritis via cartilage-bone and meniscus-bone bioscaffolds.
Applications in joint reconstruction, muscle reinforcement, and pelvic floor reconstruction are explicitly contemplated.
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