When neck and back pain becomes intractable, spinal fusion is the gold-standard treatment. However, up to 12% of these fusions fail due to infection, resulting in substantial personal and financial costs. In most cases, these infections are associated with the hardware used to stabilize the fusion. Traditionally molded or machined polyether ether ketone (PEEK) cages are widely used for this purpose due to PEEK's strength, elastic modulus comparable to bone, biocompatibility, and radiolucency. However, traditional PEEK cages and common alternatives are prone to spinal infection. Silicon nitride (Si3N4) spacers have been used in other spinal applications with an excellent antimicrobial performance history (i.e., only 0.006% of implants have been associated with infection), and they provide superior osseointegration compared to other materials. Unfortunately, Si3N4 is not ideal for stabilizing spinal fusions because the material may be susceptible to subsidence and brittle fracture. In this Phase I STTR, SINTX Technologies, in collaboration with Drexel University and Thomas Jefferson University, will combine the antimicrobial and osseointegrative properties of Si3N4 with the strength and elasticity of PEEK to develop novel 3-D-printed antimicrobial cervical cages. Development and commercialization of a 3DP Si3N4-PEEK cervical cage would address a critical unmet clinical need for an antimicrobial spinal fusion stabilizer that promotes osseointegration, withstands in vivo loading, and facilitates imaging. Aim 1. Design a 3DP Si3N4-PEEK cervical cage that meets the static loading requirements of ASTMF2077. Milestone: Demonstrate static compression, shear, and torsion strength of 3DP Si3N4-PEEK's porouscages that meets or exceeds the guidelines for cervical cages established by ASTM F2077 and benchmarked for many cage manufacturers in the literature. Aim 2. Determine antibacterial activity and osteoblast proliferation/maturation as a function of Si3N4 percentage. Milestone: A >1.5 log reduction in bacterial colonization while retaining osteoblastic proliferation/maturation. Impact - This project is expected to demonstrate the feasibility of creating cervical cages that simultaneously retain the superior radiological and biomechanical qualities of 3DP PEEK biomaterials while preserving the osseointegrative and antimicrobial qualities of Si3N4. A Phase II STTR or SBIR would advance the 3DP Si3N4-PEEK cervical cage to IDE-enabling studies, including assessments of fatigue performance, subsidence resistance, and preclinical performance in a full-scale rigorously powered in vivo model. Rationally designed antibacterial spinal cages that reliably reduce infection are critical, especially given the personal and financial costs of failed fusions as well as the increasing numbers of spinal fusions in the US due to our aging population. Milestone for Progression to Phase II - Delivery of a 3DP Si3N4-PEEK cervical cage that (1) meets the static loading requirements of ASTM F2077, (2)meets minimum performance thresholds for osseointegration, and (3) meets minimum performance thresholds for antibacterial activity. Quantitative targets are included in the Approach. PROJECT NARRATIVE Up to 12% of spinal fusion surgeries fail due to infection, resulting in substantial personal and financial costs. This study is designed to demonstrate the feasibility of addressing this challenge with new materials by combining PEEK, a common material used to stabilize spinal fusions, with silicon nitride, a medical implant material with excellent antibacterial and bone integration properties. If this new material is ultimately shown to be safe and effective in humans, it would substantially reduce the incidence of spinal fusion failure due to infection, potentially saving hundreds of millions of dollars annually and improving patient outcomes and quality of life. Adhesions ; Alkaline Phosphatase ; alkaline phosphomonoesterase ; glycerophosphatase ; Animals ; Back Pain ; Back Ache ; Backache ; Biocompatible Materials ; Biomaterials ; biological material ; Biomechanics ; biomechanical ; bone ; Bone Regeneration ; bone repair ; regenerate bone ; Cells ; Cell Body ; Ceramics ; Neck Pain ; Cervical Pain ; Cervicalgia ; Cervicalgias ; Cervicodynia ; Cervicodynias ; Neck Ache ; Neckache ; Financial cost ; Elasticity ; Escherichia coli ; E coli ; E. coli ; Ethers ; Fatigue ; Lack of Energy ; Foundations ; Fracture ; bone fracture ; Future ; Gold ; Recording of previous events ; History ; Human ; Modern Man ; Incidence ; Infection ; Ketones ; Literature ; Longevity ; Length of Life ; life span ; lifespan ; Metals ; United States National Institutes of Health ; NIH ; National Institutes of Health ; Osteoblasts ; Osteocalcin ; Bone 4-Carboxyglutamic Protein ; Bone Gla Protein ; Bone gamma-Carboxyglutamic Acid Protein ; Vitamin K-Dependent Bone Protein ; Vitamin K-Dependent Calcium-Binding Protein ; Patients ; Polymers ; Printing ; Quality of life ; QOL ; Radiology Specialty ; General Radiology ; Radiology ; Research ; Risk ; Savings ; Spinal Fusion ; Spondylosyndeses ; Staphylococcus epidermidis ; S epidermidis ; S. epidermidis ; Technology ; Temperature ; Time ; Titanium ; Ti element ; Universities ; Diagnostic radiologic examination ; Conventional X-Ray ; Diagnostic Radiology ; Diagnostic X-Ray ; Diagnostic X-Ray Radiology ; Radiography ; Roentgenography ; X-Ray Imaging ; X-Ray Medical Imaging ; Xray imaging ; Xray medical imaging ; conventional Xray ; diagnostic Xray ; diagnostic Xray radiology ; silicon nitride ; Si3N4 ; Osseointegration ; Guidelines ; base ; improved ; Cervical ; Area ; Surface ; Solid ; Clinical ; Phase ; Anti-Bacterial Agents ; Antibacterial Agents ; anti-bacterial ; antibacterial ; Collaborations ; fusion failure ; Congenital failure of fusion ; Filamentous Fungi ; Molds ; Adopted ; implant material ; Spinal ; Best Practice Analysis ; Benchmarking ; Operative Procedures ; Surgical ; Surgical Interventions ; Surgical Procedure ; surgery ; Operative Surgical Procedures ; biocompatibility ; biomaterial compatibility ; Performance ; Speed ; novel ; Property ; Manufacturer ; Manufacturer Name ; Torsion ; Address ; in vivo ; in vivo Model ; research clinical testing ; Clinical Evaluation ; Clinical Testing ; clinical test ; Patient-Focused Outcomes ; Patient outcome ; Patient-Centered Outcomes ; Small Business Innovation Research Grant ; SBIR ; Small Business Innovation Research ; Small Business Technology Transfer Research ; STTR ; Development ; developmental ; Image ; imaging ; pre-clinical ; preclinical ; mineralization ; medical implant ; Advanced Development ; design ; designing ; Joint repair ; joint reconstruction ; Resistance ; resistant ; antimicrobial ; anti-microbial ; Implant ; commercialization ; aging population ; aged population ; population aging ; standard care ; standard treatment ; 3D Print ; 3-D print ; 3-D printer ; 3D printer ; 3D printing ; three dimensional printing ; Modulus ; preservation ; osteoblast proliferation ;
