3D microprinting-enabled microinjection needle arrays for enhanced therapeutics delivery into the brain
支持 3D 微打印的显微注射针阵列可增强向大脑的治疗输送
基本信息
- 批准号:10761073
- 负责人:
- 金额:$ 40.38万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-10 至 2024-09-09
- 项目状态:已结题
- 来源:
- 关键词:3-Dimensional3D PrintAddressArchitectureBrainCellsDiffusionDimensionsEmbryoExtravasationFluorescenceGelGenesGoalsHealthHistologicHumanIn VitroIndividualIndustryIndustry StandardInjectionsLasersLateralLegal patentLentivirusMalignant NeoplasmsMarketingMeasuresMediatingMedicalMicrofluidicsMicroinjectionsModulusMusNeedlesNeurodegenerative DisordersNeurogliaNeurologicOutcomeOutputPainPenetrationPerformancePrintingProtocols documentationPuncture procedureResearchRetrievalSepharoseShapesSideSiteSolidStainless SteelSurvival RateSuspensionsTechnologyTherapeuticTissuesTraumatic Brain InjuryViral VectorWritingZebrafishbrain parenchymabrain tissueclinical applicationdesignefficacy evaluationimprovedin vivoinnovationmanufacturenanoparticlenerve stem cellnoveloperationparticlepressureprototypespinal cord and brain injurystem cell deliverystem cell survivalstem cellstissue injurytooltwo photon microscopytwo-photon
项目摘要
PROJECT SUMMARY
Microinjection technologies underlie many research and clinical applications that require gene and cell delivery,
including studies and emerging treatments of neurological conditions (e.g., neurodegenerative diseases,
traumatic brain injury, and cancer). Unfortunately, challenges associated with the microinjection tools by which
the viral vectors and cells inherent in these applications are delivered into brain tissues remain major barriers in
these rapidly growing fields. Although widely used, the currently used industry standard needles (ISNs) comprise
one needle with a single output port at the tip and are associated with a variety of validated customer pain points.
In particular, (1) the physical size of therapeutics such as lentiviral particles (80–100 nm) and stem cells (>10
μm) restricts ISN-mediated delivery into a single injection site inherently restricts the effective coverage range;
(2) the single injection site for ISNs can also result in inhomogeneous distributions of delivered therapeutics,
which can be detrimental to efficacy; and (3) the shape and size of ISNs can lead to brain tissue injury.
Consequently, alternative, novel microinjection tools for both gene and cell delivery are in critical demand.
The objective of this proposal is to develop an entirely new class of microneedle arrays (MNAs) that can be
realized to simultaneously address all three aforementioned pain points of ISNs. The working hypothesis is that
the minimal viable product (MVP) will transform microinjection outcomes via unparalleled versatility in realizing
geometrically sophisticated MNAs innovations, improve the efficacy of delivering therapeutics to the brain and
reducing microinjection-associated tissue damage. Preliminary studies demonstrated the ability of 3D
microprinting-enabled microneedle arrays (MNAs) delivery strategy to penetrate and deliver microfluidic
payloads into mouse brains. In addition, 3D-printed multi-side-port microneedles showed reduced penetration
and retrieval-associated damage to zebrafish embryos during microinjection protocols. This proposal will
examine the efficacy of this innovation to enhance fundamental performance metrics underlying both gene and
cell delivery into brain tissue. To effectively accomplish this goal, we will: 1) establish and characterize MNA
additive manufacturing protocols for novel 3D microneedle designs, 2) assess microfluidic and cell delivery
efficacy of our innovative delivery strategy versus ISNs in vitro, and 3) evaluate gene and stem cell delivery into
mouse brains mediated by our MNA innovation versus ISNs in vivo. This proposal to prototype MNA MVPs that
improve penetration, injection, and retrieval efficacy versus ISNs bridges an important need in the biomedical
industry, which will positively impact foundational human health-related research and medical applications.
项目总结
项目成果
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