Electrospun Ceramic-Polymer Composite As A Scaffold For Tissue Repair

Abstract

The present invention relates to compositions and methods of preparing a three-dimensional matrix of micron sized electrospun fibers, wherein the electrospun fibers are formed from a electrospun composite comprising a bioactive ceramic component and a polymer component. The matrix provides an osteoconductive and osteoinductive scaffold supporting osteogenesis and thereby facilitates bone repair.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Application No. 60 / 944,587, entitled “Electrospun Ceramic-Polymer Composite As A Scaffold for Tissue Repair,” filed Jun. 18, 2007, which is incorporated herein by reference in its entirety.GOVERNMENT SUPPORT[0002]This work is supported at least in part by grants to Dr. Arinzeh. The government may have certain rights in this invention.FIELD OF THE INVENTION[0003]The present invention relates to compositions and methods of preparing a three-dimensional matrix of micron sized electrospun fibers, wherein the electrospun fibers are formed from an electrospun composite comprising a bioactive ceramic component and a polymer component. The matrix provides an osteoconductive and osteoinductive scaffold supporting osteogenesis and thereby facilitates bone repair.BACKGROUND OF THE INVENTION[0004]The repair of large bone defects resulting from trauma, metabolic disorders, and tumor removal is a ...

AI Technical Summary

Benefits of technology

[0017]In another aspect, the present invention provides a method of preparing a osteoinductive scaffold to facilitate bone repair, the method comprising the steps: (a) preparing a ceramic-polymer composite comprising a bioactive ceramic component and a polymer component; (b) electrospinning the ceramic-polymer composite, and thereby (c) depositing a three-dimensional nonwoven matrix of electrospun fibers comprising the ceramic-polymer composite on a collector. According to one embodiment of the method, the electrospun composite of step (a) contains at least 10% by weight of the ceramic component. According to another embodiment of the method, the electrospun composite of step (a) contains at least about 60% by weight of the polymer component. According to another embodiment of the method, the electrospun composite contains at least 10% by weight of the ceramic component and at least about 60% by weight of the polymer component. According to another embodiment of the method, the bioactive ceramic component of the composite of step (a) contains two calcium phosphate ceramic substances for every polymer in the polymer component of the composite. According to another embodiment of the method, the calcium phosphate ceramic substances of the bioactive ceramic component of the composition of step (a) are selected from the group consisting of tetracalcium phosphate, amorphous calcium phosphate, alpha-tricalcium phosphate, beta-tricalcium phosphate, and hydroxyapatite. According to another embodiment of the method, the two calcium phosphate ceramic substances of the bioactive ceramic component of step (a) are hydroxyapatite and tricalcium phosphate. According to another embodiment of the method, the bioactive ceramic component of the composite of step (a) comprises 20% hydroxyapatite and 80% tricalcium phosphate. According to another embodiment of the method, the polymer component of the composite of step (a) is at least one polymer selected from the group consisting of a nondegradable polymer and a degradable polymer. According to another embodiment, the nondegradable polymer is selected from the group consisting of a polyurethane, a polyvinylidine fluoride, and a polyvinylidine fluoride trifluoroethylene. According to another embodiment, the degradable polymer is selected from the group consisting of poly(lactic acid-glycolic acid), poly(lactic acid), poly(glycolic acid), a poly(orthoester), a poly(phosphazene), a polycaprolactone, a polyamide, a polysaccharide, and a collagen. According to another embodiment of the method, the polymer of the polymer component of the composite of step (a) is polycaprolactone. According to another embodiment of the method, the electrospun fibers of step (c) are micron sized. According to another embodiment of the method, the matrix of electrospun fibers in step (c) comprises micron-sized pores. According to another embodiment of the method, the method further comprises the steps: (d) seeding the three-dimensional nonwoven matrix of electrospun fibers with isolated differentiable human mesenchymal cells or osteoblasts; and (e) growing the differentiable human mesenchymal cells or osteoblasts on the three-dimensional nonwoven matrix of electrospun fibers so that the differentiable human mesenchymal cells or osteoblasts differentiate into a mature cell phenotype on the scaffold.

Problems solved by technology

The repair of large bone defects resulting from trauma, metabolic disorders, and tumor removal is a major medical challenge.

However, allografts lack osteoinductive factors necessary to accelerate new bone growth and may carry the risk of disease transmission, since such grafts typically are harvested from cadavers.

Direct use of ceramics for clinical applications has been limited because of their brittleness and difficulty in shaping.

Polymer and calcium phosphate ceramic composites used in conventional scaffold-forming techniques are not easily adaptable to the electrospinning method.

Moreover, the literature in this field does not provide sufficient guidance to enable one of skill in the art of tissue engineering to adapt polymer and ceramic composites to the electrospinning method using routine experimentation.

Such mats are not optimal for osteogenesis, because these pore diameters are below the preferred range of pore sizes for cell infiltration.

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