Bone defects are commonly caused by injury or disease and can lead to a serious health condition that directly impacts the quality of life of sufferers, particularly among the aged. Bone defects up to about 1/3 inch in a large bone can heal by themselves in a healthy patient, but bone defects larger than this, or even smaller in small bones never heal completely. In order to facilitate a more complete and faster bone healing, many surgeons use bone replacement materials or bone graft to fill the defect. Bone graft materials are required to act as a scaffold which assists in integration, healing, strengthening, and improving function. After blood transfusions, bone grafts are the most important set of transplanted materials and these are usually categorized as autografts, allografts and synthetic graft materials.

Unfortunately, the majority of synthetic bone grafts developed to date are non-degradable which lead to insufficient bone formation, poor integration to the surrounding tissue, long term complications and the need for prolonged treatment with antibiotics and immunosuppressive therapies. The poor resorbability may also results in cracks and debris being given off from the synthetic implants which may trigger the onset of infection and lead to further complications. A general lack of porosity and a physiologically relevant pore size distribution in the majority of commercially available synthetic bone graft materials also restricts cellular infiltration, vascularization, and the deposition of extracellular matrix. As a result, this further limits the rate at which native mineralized bone tissues can be regenerated.

The goal of this project is to engineer a novel injectable, porous, and resorbable calcium phosphate putty (ReCaPP) using FDA approved materials that are clinically easy to adopt and extremely effective at inducing bone regeneration. This unique formulation contains a powder and a liquid which forms putty upon mixing. This injectable putty sets and hardens to a solid form in the defect site even in presence of blood and converts into nanostructured hydroxyapatite similar to natural bone. Bone defect repair frequently involves procedures with limited accessibility and visibility. Injectable and moldable materials however afford the luxury to access and operate within a site with constrained boundaries. In addition to offering minimal invasion, injectability proffers consistency to these materials for application over irregular defect sites, a fact critical for effectiveness in cranio/maxillofacial and periodontal surgeries. The set solid scaffold has sufficient mechanical stability to provide temporary support along with the host tissues throughout regeneration. The presence of interconnected pores and nanostructured hydroxyapatite in this set scaffold allows cellular infiltration and vascularization to occur and thus this scaffold resorbs at a rate similar to the rate at which native mineralized tissues are regenerated. More importantly, this putty supports bone formation as well as bone marrow generation. The putty has demonstrated full bone regeneration in rabbit ulna and calvarial models with critical sized defects (defects too large to heal on their own) by implanting ReCaPP putty, without the addition of any exogenous growth factors. The bone that is formed is identical in nature to natural bone in the body in that it is comprised of about 60% calcium phosphates and 40% bone marrow. It has also been established that bone regeneration and scaffold resorption rates using the developed putty are much higher than those of a commercial gold-standard bone void filler.

Another goal of this project is 3-D printing (also known as additive manufacturing) of scaffolds using the above mentioned patented calcium phosphate putty powder. The greatest successes in additive manufacturing including 3-D printing are currently taking place in the biomedical industry, particularly in the making of implants that take advantage of the technology’s design flexibility to match a patient’s particular needs, such as a customized jaw or hip implants. Printed three dimensional porous scaffolds mimicking the rabbit ulna bone using the ReCaPP powder has been developed. Implantation of these printed scaffolds in rabbits demonstrated the feasibility of this innovative technology for bone regeneration. Moreover, this work also showed that different biological molecules and growth factors can be incorporated into these scaffolds and can be delivered locally to improve the scaffolds integration with the existing bone as well as rapid new bone formation into the defect.

For treating bone related diseases it is highly desirable to provide a sustain release of specific therapeutic agents (e.g. vancomycin, gentamicin) directly at the bone site in need for a prolonged but desired time period. The other advantage of local targeted delivery is that the effective dosage or drug concentration can be achieved at the disease sites, while keeping the systemic drug concentration very low. This helps to avoid any drug related adverse effects to other organs. The current project has successfully developed novel biopolymer-ReCaPP based composite bone putties for long term antibiotic release. Studies showed that these composite putties not only can release antibiotics like vancomycin in a sustained and control manner over time but also form macro-pores due to degradation of the biopolymer which can also assist rapid bone regeneration.

 

References: BONE SUBSTITUTE COMPOSITIONS, METHODS OF PREPARATIONS AND CLINICAL APPLICATIONS”, P. N. Kumta, C. Sfeir and A. Roy, U.S. Patent No.: US 8,357,364 B2, Date of Patent: Jan. 22, 2013.