Functionalized calcium phosphate artificial bone and joint compositions and methods of use and manufacture
Inventors
McGowan, Kenneth A. • Gawalt, Ellen S. • Palchesko, Rachelle
Assignees
WESTMORELAND ADVANCED MATERIALS LLC • Cabertech Inc • Duquesne University of the Holy Spirit
Publication Number
US-10300167-B2
Publication Date
2019-05-28
Expiration Date
2027-03-23
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Abstract
The present invention provides a functionalized composition and resulting functionalized body or prosthesis for in vitro and in vivo use comprising at least one calcium phosphate containing phase that is functionalized with a linker group comprising at least one of an organic acid molecule, a phosphonic acid, an amine, N,N-dicyclohexylcarbodiimide, and 3-maleimidopropionic acid N-hydroxysuccinimide ester, and combinations thereof, and one or more of a chemical and/or a biologically active moieties, wherein the linker group provides for a reactive location for the attachment of the chemical or biologically active moiety, or both, to the calcium phosphate containing phase, and optionally including an unmodified and/or modified calcium aluminate containing phase. Methods of manufacturing a functionalized artificial prosthesis and methods of repairing a bone, vertebrae, or tissue structures are provided.
Core Innovation
The invention provides a functionalized composition and resulting functionalized body or prosthesis for in vitro and in vivo use, comprising at least one calcium phosphate containing phase. This phase is functionalized either on its surface or within a porous scaffold with a linker group that can include at least one of an organic acid molecule, phosphonic acid, amine, N,N-dicyclohexylcarbodiimide, and 3-maleimidopropionic acid N-hydroxysuccinimide ester, and combinations thereof. The linker group provides a reactive location for attaching chemical and/or biologically active moieties, such as proteins, antibiotics, or peptides, to the calcium phosphate containing phase. Optionally, the composition may also include an unmodified and/or modified calcium aluminate containing phase.
The composition exhibits a plastic consistency, allowing it to be molded, shaped, or pressed by hand before setting into a hard monolithic structure at ambient temperature. Porosity is controlled within the scaffold to provide vascularity and accommodation for cell growth. The compositions can be produced by molding, slipcasting, slurrycasting, vibration casting, or hand-forming, and optionally may include fibers, accelerators, retarders, surfactants, foaming agents, reactive aluminas, or combinations.
Existing artificial bones and joints, typically made from metals or apatites, face several limitations such as high production costs, poor control of porosity, and issues with integration due to differences in mechanical properties compared to natural bone. Current solutions often require additional stabilization hardware and are not optimal for host tissue integration and regeneration. The invention directly addresses these problems by enabling a customizable, biologically friendly, strong and porous artificial structure with the possibility of local functionalization to enhance bonding, support tissue growth, deliver antibiotics or biologically active agents, and mimic natural bone’s properties.
Claims Coverage
There is one independent claim defining the core inventive feature.
Functionalized calcium phosphate non-metal substrate with bidentate bond and reactive attachment sites
A functionalized composition consisting of: - At least one nonirradiated resorbable heat treated calcium phosphate non-metal substrate in the form of a monolith. - Functionalization of the surface or within at least one pore interface of the scaffold by a bidentate bond (C–O or P–O) to the calcium phosphate substrate with a carbon chain. - Attachment of one or more additional chemical moieties and/or biologically active moieties, with the bidentate bond anchoring these to the substrate, providing reactive locations for their attachment. - Properties including: - Surface area and modulus of rupture matching cancellous bone. - Plastic consistency (mechanically pliable by human hand). - Macro-porosity to support vascularity. - Hardness equal to natural bone, reducing abrasion. - Non-toxicity and infection resistance.
The claim coverage centers on a functionalized calcium phosphate monolith scaffold with bidentate linkage chemistry providing attachment sites for chemical or biologically active moieties, engineered to mimic bone in structure and function while being safe and infection-resistant.
Stated Advantages
The functionalized composition can be easily formed into complex three-dimensional shapes with a plastic consistency before hardening.
Controlled porosity supports vascularity and allows nutrients to permeate, facilitating tissue and bone integration.
The composition is mechanically strong, matches the hardness of natural bone, and reduces bone degeneration and abrasion loss at the bone-implant interface.
The composition is biocompatible, non-toxic, and supports high viability and proliferation of osteoblast-like cells and mesenchymal stem cells in vitro and in vivo.
Functionalization enables localized delivery and attachment of antibiotics, proteins, and peptides, which may reduce infection and enhance tissue regeneration.
Manufacturing is cost-effective and allows for controlled properties such as phase composition, porosity, and dissolution rates.
The compositions resist infection and can be used as bone stabilization materials with customizable biological properties.
Documented Applications
Artificial bone and artificial joint prostheses for human and animal patients.
Bone void fillers and bone graft extenders for repairing voids or defects in bone, vertebrae, or tissue structures.
Scaffolding matrices and support structures for in vitro and in vivo support of cell, tissue, organ, and nerve growth and regeneration.
Localized antibiotic delivery as an infection-resistant barrier or for targeting biofilm formation on prosthetic devices.
Three dimensional resorbable tissue scaffolds and implants, including long bone replacement and repair.
Support structure for tissue, organ, and nerve engineering using mapped patient data to create patient-specific implants.
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