This invention relates to osteoimplants and their use in the repair of bone defects and injuries. More particularly, the invention relates to a load-bearing composite osteoimplant which can assume any of a wide variety of configurations, methods for their manufacture and the use of the osteoimplants for the repair of hard tissue.
Shaped or cut bone segments have been used extensively to solve various medical problems in human and animal orthopedic surgical practice, and their application has also extended to the field of cosmetic and reconstructive surgery, dental reconstructive surgery, and other medical fields involving surgery of hard tissues. The use of autograft bone (where the patient provides the source), allograft bone (where another individual of the same species provides the source) or xenograft bone (where another individual of a different species provides the source) is well known in both human and veterinary medicine. In particular, transplanted bone is known to provide support, promote healing, fill bony cavities, separate bony elements (such as vertebral bodies), promote fusion (where bones are induced to grow together into a single, solid mass), or stabilize the sites of fractures. More recently, processed bone has been developed into shapes for use in new surgical applications, or as new materials for implants that were historically made of non-biologically derived materials.
Bone grafting applications are differentiated by the requirements of the skeletal site. Certain applications require a xe2x80x9cstructural graftxe2x80x9d in which one role of the graft is to provide mechanical or structural support to the site. Such grafts contain a substantial portion of mineralized bone tissue to provide the strength needed for load-bearing. The graft may also have beneficial biological properties, such as incorporation into the skeleton, osteoinduction, osteoconduction, or angiogenesis.
Structural grafts are conventionally made by processing, and then cutting or otherwise shaping bones collected for transplant purposes. The range of bone grafts that might be thus prepared is limited by the size and shape limitations of the bone tissue from which the bone graft originated. Certain clinically desirable shapes and sizes of grafts may thus be unattainable by the cutting and shaping processes, due to the dimensional limitations of the bone. For some shapes they may also be available only in limited amounts, due to the large variations inherent in the human or animal donor source populations.
Many structural allografts are never fully incorporated by remodeling and replacement with host tissue due, in part, to the difficulty with which the host""s blood supply may penetrate cortical bone, and partly to the poor osteoinductivity of nondemineralized bone. To the extent that the implant is incorporated and replaced by living host bone tissue, the body can then recognize and repair damage, thus eliminating failure by fatigue. In applications where the mechanical load-bearing requirements of the graft are challenging, lack of replacement by host bone tissue may compromise the graft by subjecting it to repeated loading and cumulative unrepaired damage (mechanical fatigue) within the implant material. Thus, it is highly desirable that the graft have the capacity to support load initially, and be capable of gradually transferring this load to the host bone tissue as it remodels the implant.
It is an object of the present invention to provide an osteoimplant possessing sufficient strength in a body fluid environment to enable the osteoimplant to bear loads.
It is a further object of the present invention to provide a load-bearing osteoimplant which contains pores or cavities which permit the osteoimplant to be revascularized and incorporated by the host.
It is yet a further object of the present invention to provide a load-bearing osteoimplant which is osteogenic and thereby promotes new host bone tissue formation within and around the osteoimplant.
It is yet another object of the invention to provide a load-bearing osteoimplant which supports load initially and is capable of gradually transferring this load to the host bone tissue as it remodels the osteoimplant.
It is yet another object of the invention to provide a load-bearing osteoimplant containing a reinforcing component.
It is yet an even further object of the present invention to provide methods for the manufacture of osteoimplants of any size and/or configuration ranging from the relatively simple to the relatively complex.
It is yet an even further object of the present invention to provide methods for the manufacture of bone-containing osteoimplants which are not limited by constraints imposed by the shape and/or size of the bone tissue from which the osteoimplants are manufactured.
It is still another object of the invention to provide tissue-engineered bone manufactured from one or more synthetic materials and tissue obtained from various sources such as transgenic animals, plants and microorganisms.
It is yet another object of the invention to provide an integral implant insertion instrument and implant possessing an implant portion in accordance with the invention which, following its implantation in the body, is separated from the insertion portion of the instrument.
These and further objects of the invention are obtained by a load-bearing osteoimplant which comprises a shaped, coherent aggregate of bone particles.
The load-bearing osteoimplant of this invention is fabricated by the method which comprises providing an aggregate of bone particles, optionally in combination with one or more additional components, and shaping the mass into a coherent unit of predetermined size and shape employing at least one or more processes such as extruding, molding, -solvent/gel casting, machining, computer aided design and computer aided manufacturing (CAD/CAM), and the like.
The bone particles utilized in the fabrication of the osteoimplant of this invention are selected from the group consisting of nondemineralized bone particles, demineralized bone particles and combinations thereof. The bone particles are remodeled and replaced by new host bone as incorporation of the osteoimplant progresses in vivo. As described more fully hereinbelow, the bone particles can be fully demineralized by removing substantially all of their inorganic mineral content, they can be partially demineralized by removing a significant amount, but less than all, of their inorganic mineral content or they can be superficially demineralized by confining the removal of inorganic mineral to just the surface of the bone particles.
The term xe2x80x9costeoimplantxe2x80x9d as utilized herein contemplates any device or material for implantation that aids or augments bone or other hard tissue formation or healing for human or animal use. Osteoimplants are often applied at a bone defect or dental repair site, e.g., one resulting from injury, defect brought about during the course of surgery, infection, malignancy or developmental malformation. Therefore, osteoimplants are envisioned as being suitably sized and shaped as required for use in a wide variety of orthopedic, neurosurgical, oral and maxillofacial and dental surgical procedures such as the repair of simple and compound fractures and non-unions, external and internal fixations, joint reconstructions such as arthrodesis, general arthroplasty, deficit filling, discectomy, laminectomy, anterior cervical and thoracic operations, spinal fusions, dental restorations, etc. Therefore, the osteoimplants herein are intended for implantation at a bony site and, in addition to bone particles, can contain one or more other components, e.g., binder (adhesive), filler, biologically active component, reinforcing component or reinforcing structure, coupling agent, as described in U.S. Pat. No. 6,399,693, the contents of which are incorporates by reference herein, -and the like.
The term xe2x80x9cshapingxe2x80x9d refers to any of the various methods that can be used, individually or in combination, to provide an osteoimplant of a desired size and configuration. Such methods include, for example, extruding, injection molding, solvent casting, vacuum forming, sintering, melt forming, reaction molding, compression molding, transfer molding, blow molding, rotational molding, thermoforming, machining, CAD/CAM procedures, and the like, and include any post-shaping operations that may be utilized to modify the internal and/or external structure of the osteoimplant and/or modify its properties, e.g., selective removal of a filler component to provide voids, application of a layer of biologically active material to part or all of the surface and/or subsurface region of the osteoimplant, bonding of bone particles through the crosslinking of their mutually contacting exposed collagen, etc.
The term xe2x80x9cbiocompatiblexe2x80x9d and expressions of like import shall be understood to mean the absence of stimulation of an unacceptable biological response to an implant as distinguished from the sort of mild, transient inflammation and/or granulation response which can accompany implantation of foreign objects into a living organism and which is associated with the normal healing response. Optional components that are useful can be considered biocompatible if, at the time of implantation, they are present in a sufficiently small concentration such that the above-defined condition is achieved.
The term xe2x80x9cparticlexe2x80x9d as applied to the bone component of the osteoimplant includes bone pieces of all shapes, sizes, thickness and configuration such as fibers, threads, narrow strips, thin sheets, chips, shards, powders, etc., that posses regular, irregular or random geometries. It should be understood that some variation in dimension may occur in the production of the bone particles and bone particles demonstrating considerable variability in dimensions and/or size are within the scope of this invention. Bone particles that are useful herein can be homogenous, heterogeneous and can include mixtures of human, xenogenic and/or transgenic material.
The term xe2x80x9chumanxe2x80x9d as utilized herein in reference to suitable sources of bone refers to autograft bone which is taken from at least one site in the graftee and implanted in another site of the graftee as well as allograft bone which is human bone taken from a donor other than the graftee.
The term xe2x80x9cautograftxe2x80x9d as utilized herein refers to tissue that is obtained from the intended recipient of the implant.
The term xe2x80x9callograftxe2x80x9d as utilized herein refers to tissue, which may be processed to remove cells and/or other components, intended for implantation that is taken from a different member of the same species as the intended recipient. Thus, the term xe2x80x9callograftxe2x80x9d includes bone from which substantially all cellular matter has been removed (processed acellular bone) as well as cell-containing bone.
The term xe2x80x9cxenogenicxe2x80x9d as utilized herein refers to material intended for implantation obtained from a donor source of a different species than the intended recipient. For example, when the implant is intended for use in an animal such as a horse (equine), xenogenic tissue of, e.g., bovine, porcine, caprine, etc., origin may be suitable.
The term xe2x80x9ctransgenicxe2x80x9d as utilized herein refers to tissue intended for implantation that is obtained from an organism that has been genetically modified to contain within its genome certain genetic sequences obtained from the genome of a different species.
The term xe2x80x9ccompositexe2x80x9d as utilized herein refers to the mixture of materials and/or components used in preparing the shaped osteoimplant.
The term xe2x80x9cwholexe2x80x9d as utilized herein refers to bone that contains its full, or original, mineral content.
The term xe2x80x9cdemineralizedxe2x80x9d as utilized herein refers to bone containing less than about 95% of its original mineral content and is intended to cover all bone particles that have had some portion of their original mineral content removed by a demineralization process. Non-demineralized bone particles provide strength to the osteoimplant and allow it to initially support a load. Demineralized bone particles induce new bone formation at the site of the demineralized bone and permit adjustment of the overall mechanical properties of the osteoimplant.
The expression xe2x80x9cfully demineralizedxe2x80x9d as utilized herein refers to bone containing less than about 8% of its original mineral context.
The term xe2x80x9costeogenicxe2x80x9d as utilized herein shall be understood as referring to the ability of an osteoimplant to enhance or accelerate the growth of new bone tissue by one or more mechanisms such as osteogenesis, osteoconduction and or osteoinduction.
The term xe2x80x9costeoinductivexe2x80x9d as utilized herein shall be understood to refer to the ability of a substance to recruit cells from the host that have the potential for forming new bone and repairing bone tissue. Most osteoinductive materials can stimulate the formation of ectopic bone in soft tissue.
The term xe2x80x9costeoconductivexe2x80x9d as utilized herein shall be understood to refer to the ability of a non-osteoinductive substance to serve as a suitable template or substrate along which bone may grow.
The term xe2x80x9costeoimplantxe2x80x9d herein is utilized in its broadest sense and is not intended to be limited to any particular shape, size, configuration or application.
The term xe2x80x9cshapexe2x80x9d as applied to the osteoimplant herein refers to a determined or regular form or configuration in contrast to an indeterminate or vague form or configuration (as in the case of a lump or other solid mass of no special form) and is characteristic of such materials as sheets, plates, disks, cores, pins, screws, tubes, teeth, bones, portions of bones, wedges, cylinders, threaded cylinders, cages, and the like. . This includes forms ranging from regular, geometric shapes to irregular, angled, or non-geometric shapes, and combinations of features having any of these characteristics.
The term xe2x80x9cimplantablexe2x80x9d as utilized herein refers to a biocompatible device retaining potential for successful surgical placement within a mammal.
The expression xe2x80x9cimplantable devicexe2x80x9d and expressions of like import as utilized herein refers to any object implantable through surgical, injection, or other suitable means whose primary function is achieved either through its physical presence or mechanical properties.
The term xe2x80x9cbioresorbablexe2x80x9d as utilized herein refers to those materials of either synthetic or natural origin which, when placed in a living body, are degraded through either enzymatic, hydrolytic or other chemical reactions or cellular processes into by-products which are either integrated into, or expelled from, the body. It is recognized that in the literature, the terms xe2x80x9cresorbablexe2x80x9d, xe2x80x9cabsorbablexe2x80x9d, and xe2x80x9cbioabsorbablexe2x80x9d are frequently used interchangeably.
The term xe2x80x9cpolymericxe2x80x9d as utilized herein refers to a material of natural, synthetic or semisynthetic origin that is made of large molecules featuring characteristic repeating units.
The expression xe2x80x9calternating copolymersxe2x80x9d as utilized herein refers to copolymers with a regular or alternating repeating unit sequence The expression xe2x80x9cthermoplastic elastomersxe2x80x9d as utilized herein refers to melt-processable copolymers which possess elastomeric mechanical properties as a result of a crystallizable xe2x80x9chardxe2x80x9d segment and an amorphous xe2x80x9csoftxe2x80x9d segment possessing a Tg below its service temperature.
The term xe2x80x9cblendsxe2x80x9d as utilized herein refers to polymeric materials that are melt-mixed to achieve compounding between two or more different polymeric compositions that are not covalently bonded to each other. For the purposes of this application, a melt-miscible blend is a polymeric mixture that possesses sufficient miscibility in the melt to be useful in shaping.
The term xe2x80x9cincorporationxe2x80x9d utilized herein refers to the biological mechanism whereby host cells gradually remove portions of the osteoimplant and replaces the removed portions with native host bone tissue while maintaining strength. This phenomenon is also referred to in the scientific literature by such expressions as xe2x80x9ccreeping substitution,xe2x80x9d xe2x80x9cwound healing responsexe2x80x9d and xe2x80x9ccellular based remodeling.xe2x80x9d Therefore, the term xe2x80x9cincorporationxe2x80x9d shall be understood herein as embracing what is considered by those skilled in the art to be conveyed by the aforequoted expressions.
The expression xe2x80x9cfurther treatmentxe2x80x9d as utilized herein refers to procedures such as lyophilization, cross-linking, re-mineralization, sterilization, etc., performed either before, during or after the step of shaping the bone particle-containing aggregate as well as post-process procedures such as machining, laser etching, welding, assembling of parts, cutting, milling, reactive etching, etc. It further includes treatment(s) applied at the time of surgery such as rehydration, combining with cellular materials, application of growth factors, etc.
The expression xe2x80x9cwet compressive strengthxe2x80x9d as utilized herein refers to the compressive strength of the osteoimplant after the osteoimplant has been immersed in physiological saline (water containing 0.9 g NaCl/100 ml water) for a minimum of 12 hours and a maximum of 24 hours. Compressive strength is a well known measurement of mechanical strength and is measured using the procedure described herein.