Injectable composition for in-situ repair and regeneration of an injured ligament or tendon and methods of use
Inventors
Chang, James • Pham, Hung • Woon, Colin • Farnebo, Simon • Legrand, Anais
Assignees
US Department of Veterans Affairs • Leland Stanford Junior University
Publication Number
US-9925308-B2
Publication Date
2018-03-27
Expiration Date
2034-03-14
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Abstract
The invention provides an injectable composition and method for the minimally invasive, in-situ repair and regeneration of an injured ligament or tendon in a mammalian subject. The composition is also useful for the delivery of growth factors, therapeutic agents and cells into the area of tendon or ligament injury.
Core Innovation
The invention provides an injectable composition and method for the minimally invasive, in-situ repair and regeneration of an injured ligament or tendon in a mammalian subject. This composition comprises decellularized extracellular matrix derived from tendon connective tissue that is in an injectable form below 25 degrees Celsius and polymerizes upon administration into the injured ligament or tendon area to form a hydrogel. The hydrogel fills and conforms to the defect, creating a support structure that facilitates infiltration and recruitment of the subject's own fibroblasts, tenoblasts, and tenocytes to aid in tissue repair and regeneration.
The problem being solved arises from the frequent occurrence of tendon and ligament injuries, including microscopic tears from overuse and acute tears from trauma, which lead to altered biomechanical properties and impaired healing. Current treatments require materials that are readily available for quick, efficient, and minimally invasive administration to assist tissue recovery, especially for common injuries of the rotator cuff, Achilles tendon, quadriceps tendon, and epicondylitis of the elbow. The invention addresses this need by providing a tendon-derived composition that can be injected in solubilized form and forms an in-situ scaffold promoting natural tissue healing and regeneration.
Claims Coverage
The patent includes three independent claims presenting compositions and methods for in-situ repair and regeneration of injured ligaments or tendons.
Injectable tendon-derived extracellular matrix composition that forms an in-situ repair scaffold
A composition comprising decellularized extracellular matrix derived from tendon connective tissue by enzymatic digestion at ambient temperature, which is injectable below 25°C and forms a gel upon administration into an injured ligament or tendon area. The gel creates a support structure facilitating infiltration of the subject's own fibroblasts and tenocytes for tissue repair and regeneration without involving bone formation.
Method of producing a decellularized tendon extracellular matrix composition
A method for producing a composition for in-situ repair and regeneration comprising (a) processing donor tendon connective tissue without thermal denaturation to obtain decellularized tendon extracellular matrix, and (b) milling, powderizing, and enzymatically treating the tendon extracellular matrix at ambient temperature.
The claims cover injectable decellularized tendon matrix compositions that polymerize in situ to form scaffolds which promote cell infiltration for tendon or ligament repair, as well as methods for preparing such compositions without thermal denaturation, emphasizing enzymatic digestion at ambient temperature and milled tendon-derived extracellular matrix.
Stated Advantages
The composition allows minimally invasive, rapid, and localized administration through injection, providing an efficient treatment accessible in outpatient settings without requiring surgery.
The thermosensitive nature enables storage of the tendon extracellular matrix in liquid form at low temperatures with gelation triggered at physiological body temperature, facilitating ease of use and site-specific scaffold formation.
The scaffold formed supports host cell infiltration, guiding renewal of tenoblasts, tenocytes, and fibroblasts, promoting organized tissue regeneration that restores normal biomechanical and functional properties.
The composition can be supplemented with cells and therapeutic agents such as growth factors, antibiotics, and analgesics to enhance tissue repair and address infection or pain associated with tendon or ligament injury.
Use of allogeneic or xenogeneic sources such as human or porcine tissues provides high availability and cost-effectiveness, while maintaining biocompatibility and biomechanical suitability for repair.
Documented Applications
In-situ repair and regeneration of acute or chronic injuries of ligaments and tendons including Achilles tendon, rotator cuff, patellar tendon, common flexor tendon, and common extensor tendon.
Delivery vehicle for cells such as stem cells, fibroblasts, or progenitor cells combined with the tendon-derived matrix to enhance tissue regeneration in musculoskeletal injuries.
Carrying therapeutic agents including growth factors (e.g., bFGF, VEGF), platelet-rich plasma, antibiotics, and analgesics into the injury site for improved healing outcomes.
Treatment of tendon overuse injuries and tendinopathies as well as ligament injuries that commonly occur in sports medicine and physical therapy contexts.
Creation of nanoscale collagen fiber hydrogels (nanogel) via high-frequency ultrasonication of the tendon extracellular matrix solution to enhance cellular integration and scaffold properties for improved regenerative applications.
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