Drug-eluting joint implants with synergistic antimicrobial release and risk stratified models of preclinical efficacy testing
具有协同抗菌释放功能的药物洗脱关节植入物和临床前疗效测试的风险分层模型
基本信息
- 批准号:10593923
- 负责人:
- 金额:$ 36.74万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-04-01 至 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:AmputationAnalgesicsAnti-Bacterial AgentsAntibioticsAntioxidantsArthrodesisAttentionBacterial InfectionsBiomedical EngineeringBiometryBone CementsBupivacaineCaringClinicalCommunicable DiseasesComplicationDataDevicesEconomic BurdenEngineeringExcisionFailureFormulationGentamicinsGoalsGrowthHealthHealthcareImmobilizationImplantIn VitroInfectionInflammatoryJointsKetorolacKnowledgeLifeLinkMechanicsMedical DeviceMethodsMicrobial BiofilmsMissionModalityModelingMorbidity - disease rateMorphologyNatureNon-Steroidal Anti-Inflammatory AgentsOperating RoomsOperative Surgical ProceduresOralOrgan TransplantationOrganismOrthopedic SurgeryOrthopedicsOutcomePatientsPeriprosthetic joint infectionPharmaceutical PreparationsPolymersPre-Clinical ModelPreventionProbabilityProceduresPropertyPublic HealthQuality of lifeRattusRecurrenceReplacement ArthroplastyResearchResistanceRiskRisk AssessmentSafetyStaphylococcal InfectionsStaphylococcus aureusSurfaceSystemTechnologyTestingTherapeuticTimeTreatment CostTreatment FailureUnited States National Institutes of HealthVancomycinWeight-Bearing stateWorkalternative treatmentantimicrobialantimicrobial drugcare burdenchemotherapyclinical developmentclinically relevantcontrolled releasecostcrosslinkdesigndisabilityefficacy testingimmunological statusimplant materialimplantationimplementation strategyimprovedimproved outcomein vivoinnovationjoint infectionmechanical propertiesmicroorganismmortalitynovelpharmacodynamic modelpre-clinicalpreventrecurrent infectionrisk stratificationsample fixationstandard caresynergismtechnology platformtreatment durationtreatment riskultra-high molecular weight polyethylene
项目摘要
Project Summary/Abstract
There is a fundamental gap in understanding the effect of local delivery of antibiotics for the prevention and
treatment of peri-prosthetic joint infections, a truly morbid and costly complication threatening >1 million
patients undergoing joint arthroplasty each year. There is currently no fully load-bearing medical device which
can also be used for the controlled release of antibiotics to treat peri-prosthetic joint infection (PJI). The current
standard of treatment (there is none for prevention) involves a two-stage revision during which patients are
immobilized for more than 3 months. Available treatments are effective only about 40-80% of the time with
recurrence increasing morbidity, mortality and cost tremendously. There is a great need to improve outcomes,
patients’ quality of life and to reduce cost.
Our long-term goal is to develop materials and methods to enable and thoughtfully control the local release of
therapeutics to treat orthopaedic conditions. The overall objective of this application is to devise an antibiotic-
eluting and load-bearing joint implant platform technology and its implementation strategy to improve the
treatment of PJI. Our central hypothesis is that by manipulating the synergy of incorporated drugs,
drug/polymer interactions and drug incorporation methods, an ultrahigh molecular weight polyethylene
(UHMWPE) implant with optimal antibiotic efficiency and safety can be designed. The rationale for the
proposed research is that by using a newly discovered antibiotic synergy between local PJI antibiotics and
commonly used analgesics, we can optimize drug elution profiles with maximum efficacy in preventing the
growth of clinically relevant infections of variable risk. This strategy has the potential of changing the treatment
paradigms for improved outcomes without any additional risks to patients. The specific aims are (1) identifying
the factors in engineering UHMWPE with synergistic antibacterial release and (2) developing preclinical risk-
stratification tests for the implementation of antibiotic-eluting UHMWPE. The challenge of developing a tough,
fully load-bearing and wear resistant surface while incorporating drugs in the polymer will be overcome by two
strategies: introducing highly eccentric drug clusters that enable lower drug loading and spatially limiting the
drug-loaded regions to low load bearing regions of the implant. The approach is innovative firstly because it
departs from the current methods of depending on antibiotic elution from temporary, non-weight bearing bone
cement devices often assembled in the operating room and secondly because analgesics, which can improve
the efficacy of antibiotics, can be delivered concurrently at a predetermined rate using this device. The
expected outcome is a platform bearing surface technology and an implementation strategy tailored to the
infecting microorganism. The strategies capitalize on the team’s expertise in the development of clinically used
UHMWPE implants based on innovations in antioxidant stabilization, cross-linking and morphology
manipulation. We present strong preliminary data showing the feasibility of our ideas including incorporating
vancomycin in UHMWPE with safe and efficient release in pre-clinical planktonic and biofilm infection models
and the synergy between the analgesic drugs ketorolac and bupivacaine with gentamicin. The proposed
research is significant, because it is expected to provide a new, safe and efficient implant for combating PJI,
which can eliminate the costly and burdensome gold standard of two-stage revision with temporary
immobilization.
项目总结/文摘
项目成果
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{{ truncateString('Ebru Oral', 18)}}的其他基金
Drug-eluting joint implants with synergistic antimicrobial release and risk stratified models of preclinical efficacy testing
具有协同抗菌释放功能的药物洗脱关节植入物和临床前疗效测试的风险分层模型
- 批准号:
10372936 - 财政年份:2020
- 资助金额:
$ 36.74万 - 项目类别:
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