Demineralized bone fibers and preparation thereof
Inventors
Chen, Silvia • Cleavenger, Grant • Phelps, Dennis • Wralstad, Evans • Gjurich, Breanne • JOHNSON, Austin • Sampson, Alana • Entsminger, Adam • Chen, Jingsong
Assignees
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Publication Number
US-12090250-B2
Publication Date
2024-09-17
Expiration Date
Abstract
The present invention provides demineralized bone fibers exhibiting optimal handling properties (e.g., high moldability and low elastic modulus) and biological activities (e.g., osteoinductivity) as well as non-demineralized bone fibers useful for preparing the demineralized bone fibers. A well-controlled demineralization process for preparing the demineralized bone of fibers is also provided. Products comprising the demineralized bone fibers and uses thereof are further provided.
Core Innovation
The invention relates to demineralized bone fibers (DBM fibers) and a method for preparing a demineralized bone graft in which a residual calcium content of the demineralized bone graft is less than 6 wt % based on dry weight. The method comprises subjecting a non-demineralized bone graft to a single incubation in an acid solution having a pH of 0-4 for no more than 300 seconds. Demineralization is performed with a single-pulse acid demineralization approach to achieve low residual calcium.
The document further describes DBM fibers prepared from non-demineralized bone fibers via a well-controlled single-pulse acid demineralization (SPAD) process. The demineralized bone fibers are characterized by improved handling properties including high moldability and low elastic modulus, while remaining osteoinductive.
In addition, the document reports biological activity and retention of bone morphogenetic proteins (BMPs) associated with the DBM fibers, including retention assays using BMP-2 and BMP-7. The described SPAD-derived DBM fibers show improved osteoinductivity in an athymic nude mouse implant model, with higher osteoinductive scores compared to a comparative condition.
The document also supports product formats including compositions, implants, and packaging, including jar, pouch, tray, and syringe, and describes combining the demineralized bone fibers with and storing them in glycerol. The overall invention integrates low residual calcium achieved by single acid incubation, defined fiber and composition characteristics, and biological performance of osteoinductive DBM fibers.
Claims Coverage
The document includes three independent claim sets: a method for preparing a demineralized bone graft, a composition of osteoinductive demineralized bone fibers, and a method for preparing a demineralized bone graft that further requires combining and storing in glycerol. Across these independent claims, the inventive features center on single incubation in an acid solution (pH 0-4, ≤300 seconds) to achieve residual calcium <6 wt % (dry weight), and on composition/product constraints such as residual calcium range, specific area, osteoinductivity, and glycerol storage.
Single acid incubation to achieve low residual calcium
Subjecting a non-demineralized bone graft to a single incubation in an acid solution for no more than 300 seconds, wherein the acid solution has a pH of 0-4, to form a demineralized bone graft having a residual calcium content of less than 6 wt % based on the dry weight.
Osteoinductive demineralized bone fiber composition with defined residual calcium and specific area
Providing a composition comprising osteoinductive demineralized bone fibers having a residual calcium content of between 0.5-6 wt % based on the dry weight, wherein the demineralized bone fibers have a specific area 185-5,550 cm2/g, and wherein the demineralized bone fibers are combined with and stored in glycerol.
Single acid incubation with glycerol combination and storage
Subjecting a non-demineralized bone graft to a single incubation in an acid solution for no more than 300 seconds, wherein the acid solution has a pH of 0-4, to form a demineralized bone graft having a residual calcium content of less than 6 wt % based on the dry weight, and combining the demineralized bone graft with and storing it in glycerol.
The independent claim coverage is grounded in achieving residual calcium below 6 wt % by a single incubation in a pH 0-4 acid solution for no more than 300 seconds, and in forming osteoinductive demineralized bone fiber compositions characterized by defined residual calcium, specific area, and glycerol combination/storage.
Stated Advantages
Improved handling properties including high moldability and low elastic modulus of the DBM fibers.
Increased osteoinductivity in an athymic nude mouse implant model, with significantly higher osteoinductive scores.
Retention of osteoinductive BMP activity, including BMP-2 and BMP-7 retention assays.
Documented Applications
Implantation/application in an athymic nude mouse implant model (biceps femoris/gluteus) to assess osteoinductivity of SPAD-derived DBM fibers.
Composition/implant product formats including packaging formats such as jar, pouch, tray, and syringe.
Tissue/organ defect treatment by applying an effective amount of the composition to a defect site in a subject.
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