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Publication Number
US-11890396-B2
Publication Date
2024-02-06
Expiration Date
Abstract
Provided herein is a living bone graft including a biofabricated graft core including demineralized bone matrix and a carrier and a pre-vascularized shell at least partially enrobing the graft core, the pre-vascularized shell including isolated, intact adipose-derived microvessel fragments, mesenchymal stem cells, and collagen. The disclosed bone grafts include stromal cells that differentiate and microvessels that inosculate to provide a functional microvasculature, thereby approximating native bone repair as the graft matures in the patient. Also provided herein are methods of fabricating a bespoke, living, vascularized bone graft and methods of treating a segmental bone defect in a patient.
Core Innovation
The invention provides a bone graft that includes a 3D printed graft core formed of a pre-bone constituent comprising demineralized bone matrix (DBM) and a carrier. The graft core is at least partially enrobed by a pre-vascularized shell formed from a pre-vascularized shell constituent comprising isolated intact microvessel fragments, mesenchymal stem cells, and collagen.
The pre-vascularized shell constituent includes isolated intact microvessel fragments in a specified concentration range, combined with mesenchymal stem cells and collagen in a specified concentration range. The microvessel fragments are configured to inosculate such that the bone graft progresses to native, mature, vascularized bone in a patient.
The document describes the construct as a bespoke/custom graft formed to approximate native periosteum/repair for segmental bone defect treatment. It further describes optional features including a biofabricated DBM/carrier graft core with optional fibrinogen/gelatin and optional MSCs, and optional ectopic “banking” prior to implantation.
Claims Coverage
The partial content includes three independent claims that collectively cover a bone graft structure, a method of fabricating the living bone graft, and a method of treating a segmental bone defect. Across these independent claims, the inventive features are centered on the pre-bone DBM/carrier core, the pre-vascularized shell with isolated intact microvessel fragments plus mesenchymal stem cells and collagen, and the use of this construct to drive inosculation and maturation in a patient.
3D printed pre-bone graft core with DBM and carrier and pre-vascularized shell enrobing
A bone graft comprising a 3D printed graft core formed of a pre-bone constituent comprising demineralized bone matrix (DBM) and a carrier, and a pre-vascularized shell at least partially enrobing the graft core.
Pre-vascularized shell constituent with isolated intact microvessel fragments, mesenchymal stem cells, and collagen
The pre-vascularized shell formed of a pre-vascularized shell constituent comprising isolated intact microvessel fragments, mesenchymal stem cells, and collagen.
Biofabricating a living bone graft via 3D-printed DBM/carrier core, first incubation, shell enrobing, and second incubation
A method of fabricating a bone graft comprising biofabricating via 3D-printing a graft core from a pre-bone constituent comprising demineralized bone matrix (DBM) and a carrier; incubating the graft core in a first culture medium comprising a crosslinker; enrobing at least a portion of the graft core with a pre-vascularized shell constituent comprising isolated intact microvessel fragments, mesenchymal stem cells, and collagen; and incubating the enrobed graft core in a second culture medium to provide a living bone graft.
Treating a segmental bone defect with a pre-vascularized DBM/carrier graft
A method of treating a segmental bone defect in a patient comprising providing a bone graft with a 3D-printed graft core formed of a pre-bone constituent comprising demineralized bone matrix (DBM) and a carrier, and a pre-vascularized shell at least partially enrobing the graft core, and placing the bone graft in a segmental bone defect region of the patient, wherein the microvessel fragments inosculate and the bone graft progresses to native, mature bone in the patient.
Collectively, the independent claims are directed to a graft architecture with a 3D printed DBM/carrier pre-bone core and a pre-vascularized shell, a fabrication method for producing the living graft, and a treatment method in which placement in a segmental bone defect region results in microvessel fragment inosculation and progression to native, mature bone.
Stated Advantages
Supports microvessel inosculation and progression to native mature, vascularized bone in a patient.
Approximates native periosteum/repair for segmental bone defect treatment.
Documented Applications
Use in treating a segmental bone defect in a patient by placing the graft in the segmental bone defect region so microvessel fragments inosculate and the graft progresses to native, mature bone in the patient.
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