Project Grant R43DE031456

DEVELOPMENT AND PRE-CLINICAL TESTING OF PEKK/SILICON NITRIDE COMPOSITE CRANIOMAXILLOFACIAL IMPLANTS - PROJECT SUMMARY-OVER 235,000 AMERICANS UNDERGO CRANIOMAXILLOFACIAL (CMF) SURGERY ANNUALLY, WITH IMPLANT FAILURE RATES AVERAGING 5.5% IN GENERAL AND UP TO 37% AND 52% IN THE ORBITAL AND TEMPORAL REGIONS, RESPECTIVELY. FAILURES ARE ATTRIBUTED TO PROSTHETIC INFECTIONS, POOR OSSEOINTEGRATION, CORROSION, AND FRACTURE. MOST CAN BE LINKED TO IMPLANT MATERIALS THAT UNDERPERFORM IN TERMS OF BIOACTIVITY, INFECTION CONTROL, OSSEOUS INTEGRATION, OR MECHANICAL STABILITY. THUS, THERE CONTINUES TO BE A CRITICAL CLINICAL NEED FOR MEDICAL IMAGING COMPATIBLE 3DP BIOMATERIALS FOR CRANIOMAXILLOFACIAL OSTEOPLASTY THAT CAN BE PERSONALIZED, PROMOTE INTEGRATION, AND PREVENT INFECTION. SINTX TECHNOLOGIES, INC. PIONEERED THE USE OF SILICON NITRIDE (SI3N4) AS A HIGH-PERFORMANCE ALTERNATIVE TO METAL AND POLYMER-BASED BIOMATERIALS FOR BONE AND JOINT REPAIR. SI3N4 IS A PROMISING BIOMATERIAL FOR CMF DEFECTS BECAUSE OF ITS ANTIBACTERIAL ACTIVITY, OSSEOINTEGRATION, RADIOGRAPHIC IMAGING, AND DURABILITY, BUT THE STIFFNESS OF SI3N4 ENGENDERS STRESS SHIELDING AND MAY BE SUSCEPTIBLE TO SUBSIDENCE AND BRITTLE FRACTURE. IN CONTRAST, PEEK AND PEKK ARE MORE FLEXIBLE, RADIOTRANSPARENT BIOMATERIALS, BUT THESE POLYMERS LACK ANTIMICROBIAL AND OSSEOINTEGRATIVE PROPERTIES. TO OVERCOME THESE LIMITATIONS, SINTX PROPOSES TO COMBINE ITS BIOACTIVE SI3N4 WITH PEKK TO FORM A 3D-PRINTABLE COMPOSITE THAT WILL BE RADIOLUCENT, POSSESS AN ELASTIC MODULUS SIMILAR TO CORTICAL BONE, AND SIMULTANEOUSLY PROVIDE IMPROVED ANTIMICROBIAL AND OSTEOINTEGRATION PROPERTIES. THE PURPOSE OF THIS APPLICATION IS TO DESIGN, BUILD, AND TEST 3DP PEKK/SI3N4 COMPOSITE FOR NON-LOAD-BEARING CMF IMPLANTS THAT SATISFY MATERIAL REQUIREMENTS AND ENHANCE INFECTION RESISTANCE AND OSSEOUS INTEGRATION. AIM 1. DESIGN, PRODUCE, AND CHARACTERIZE POROUS 3DP PEKK/SI3N4 IMPLANTS FOR NON-LOAD-BEARING CMF APPLICATIONS. MILESTONES: 1) PREPARE PEKK/SI3N4 COMPOSITE FILAMENTS BASED ON A RANGE OF PEKK/SI3N4 VOLUME RATIOS; 2) DESIGN AN APPROPRIATE CMF IMPLANT BASED ON THE AMOUNT AND TYPE OF INCLUDED POROSITY; 3) VALIDATE THE 3D PRINTABILITY OF THE VARIOUS PEKK/SI3N4 COMPOSITES; AND 4) ASSESS THE PHYSICAL AND MECHANICAL PROPERTIES OF THE 3DP CMF COMPOSITE DESIGNS. AIM 2. COMPLETE IN VITRO ANTIBACTERIAL AND OSTEOCONDUCTIVITY TESTING OF THE PREFERRED 3DP PEKK/SI3N4 IMPLANT FROM AIM 1. MILESTONES: DEMONSTRATE THAT TEST COMPONENTS FROM THE PREFERRED 3DP PEKK/SI3N4 IMPLANT 1) ACHIEVE A = 1.5-LOG10 REDUCTION IN STAPHYLOCOCCUS EPIDERMIDIS (S. EPIDERMIDIS) AND ESCHERICHIA COLI (E. COLI); AND 2) DEMONSTRATE AN ABILITY TO SIGNIFICANTLY UPREGULATE OSTEOBLASTIC ACTIVITY. AIM 3. TEST THE IN VIVO ANTIMICROBIAL EFFECTIVENESS AND OVERALL HEALING OF THE 3DP PEKK/SI3N4 IMPLANT COMPARED TO PEEK. MILESTONES: 1) PREPARE AND CHARACTERIZE IDENTICAL 3DP PARTIALLY POROUS PEKK/SI3N4 AND PEEK IMPLANTS; AND 2) COMPLETE A 28-DAY IN VIVO TIME-COURSE STUDY OF THESE IMPLANTS UNDER ASEPTIC AND SEPTIC CONDITIONS IN WISTAR RATS. IMPACT - THIS PROOF-OF-CONCEPT PROJECT IS EXPECTED TO PROVIDE STRONG RATIONALE AND PRELIMINARY DATA TO SUPPORT FURTHER STUDY AND COMMERCIALIZATION OF A 3D-PRINTABLE PEKK/SI3N4 COMPOSITE FOR CMF IMPLANTS, WHICH COULD SUBSTANTIALLY REDUCE IMPLANT FAILURES DUE TO INFECTION AND/OR POOR BONE INTEGRATION.