Bone graft and methods of fabrication and use
AssigneeAdvanced Solutions Life Sciences, LLC
InventorsJames B. Hoying, Sarah Moss
Life of this patent
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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.
Claims24
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, the pre-vascularized shell formed of a pre-vascularized shell constituent comprising:
- from about 80,000 to about 500,000 microvessels/ml isolated intact microvessel fragments,
- mesenchymal stem cells, and
- from about 1.5 to about 7 mg/ml collagen.
A method of fabricating a bone graft, the method comprising:
- (a) biofabricating via 3D-printing a graft core from a pre-bone constituent comprising demineralized bone matrix (DBM) and a carrier;
- (b) incubating the graft core in a first culture medium comprising a crosslinker for a first incubation period;
- (c) enrobing at least a portion of the graft core with a pre-vascularized shell constituent comprising from about 80,000 to about 500,000 microvessels/ml isolated intact microvessel fragments, mesenchymal stem cells, and from about 1.5 to about 7 mg/ml collagen;
- and
- (d) incubating the enrobed graft core of step (c) in a second culture medium for a second incubation period to provide a living bone graft.
A method of treating a segmental bone defect in a patient, the method comprising:
- providing 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, the pre-vascularized shell formed of a pre-vascularized shell constituent comprising from about 80,000 to about 500,000 microvessels/ml isolated intact microvessel fragments, mesenchymal stem cells, and from about 1.5 to about 7 mg/ml collagen;
- 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.
Dependencies are inferred from the claim text.