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Controlled Vascularization Using Acoustic Droplet-Hydrogel Composites

使用声学液滴-水凝胶复合材料控制血管化

基本信息

批准号：
8866359
负责人：
Mario Leonardo Fabiilli
金额：
$ 13.64万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-01 至 2017-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8866359
关键词：
Acoustics Anastomosis - action Behavior Bladder Blood Vessels Bolus Infusion Cartilage Clinical Clinical Trials Data Diffuse Drug Formulations Emulsions Encapsulated Exhibits Exposure to Fibroblast Growth Factor 2 Gases Generations Goals Growth Growth Factor Health Hindlimb Hour Hydrogels Implant Injection of therapeutic agent Injury Ischemia Kinetics Limb structure Liquid substance Methods Mission Modeling Morbidity - disease rate Necrosis Nutrient Operative Surgical Procedures Organ Transplantation Outcome Oxygen Pain Patients Pattern Pericytes Public Health Research Risk Route Site Skin System Technology Testing Therapeutic Agents Time Tissue Engineering Tissues Toxic effect Translating Translations Ultrasonography United States National Institutes of Health Vascular Endothelial Cell Vascular blood supply Vascularization Wound Healing angiogenesis base clinically relevant controlled release cost human FGF3 protein improved in vivo migration millimeter mortality novel platelet-derived growth factor BB prevent reconstruction regenerative response scaffold success tissue regeneration tissue support frame vaporization wound

项目摘要

DESCRIPTION: The viability, and hence clinical utility of an engineered tissue implant relies on rapid integration with the blood supply of the recipient. Angiogenic growth factors including basic fibroblast growth factor (bFGF) and platelet- derived growth factor-BB (PDGF-BB) are critical regulators of vascular invasion. During wound healing, these growth factors exhibit spatially- and temporally-restricted patterns of expression. The administration of angiogenic growth factors by conventional methods has yielded limited success in promoting clinically-relevant vascular responses to implants - in part because these methods provide minimal control over the timing and localization of growth factor activity. The long-term goal is to use ultrasound to actively control cellular behavior - such as migration, survival, proliferation, and differentiatio - involved in tissue regeneration thus enhancing construct viability and functionality. Ultrasound is ideally suited to modulate cellular activities within implanted scaffolds since it can be applied non-invasively, focused with sub-millimeter precision, delivered in a spatio-temporally controlled manner to sites deep within the body, and translated clinically. The objective of this application is to use ultrasound - specifically a mechanism termed acoustic droplet vaporization (ADV) - to generate tightly controlled vascularization within an implanted tissue scaffold via the controlled release of angiogenic growth factors. ADV is a phenomenon whereby emulsified liquid droplets are converted into gas bubbles upon exposure to ultrasound above a certain acoustic amplitude. Therapeutic agents, encapsulated within the emulsion, are released upon ADV. The central hypothesis is that ADV can be used to spatio- temporally control the release of encapsulated bFGF and PDGF-BB within an implanted tissue scaffold. The rationale for the proposed research is that ADV enables the sequential release of bFGF and PDGF-BB, which exhibit mutual antagonism when presented simultaneously but synergistically enhance vascular growth when presented sequentially. Guided by strong preliminary data, the hypothesis will be tested via three specific aims: 1) Develop acoustically-sensitive emulsion formulations with distinct release thresholds; 2) Demonstrate vascular in-growth in a subcutaneously implanted composite scaffold following the ultrasound-triggered release of bFGF; and 3) Demonstrate vascular in-growth in an ischemic hind limb model following the sequential release of bFGF and PDGF-BB at the site of vascular injury. Overall, the two growth factor delivery system optimized in the first aim will be evaluated in vivo using ectopic and orthotopic models in the second and third aims, respectively. Successful completion of these studies is significant since controlled release of angiogenic growth factors and subsequent vascularization within scaffolds is expected to facilitate the clinical translation of engineered tissue. Ultimately, this ultrasound-responsive scaffold system is a platform technology that could enable spatial and temporal control over the release of other regenerative growth factors critical for tissue regeneration and integration.

描述：工程组织植入物的生存能力和临床应用依赖于与受体血液供应的快速整合。血管生成生长因子包括基本的

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Use of Hydroxyapatite Doping to Enhance Responsiveness of Heat-Inducible Gene Switches to Focused Ultrasound.

使用羟基磷灰石掺杂增强热诱导基因开关对聚焦超声的响应性。

DOI：
10.1016/j.ultrasmedbio.2015.11.006
发表时间：
2016
期刊：
Ultrasound in medicine & biology
影响因子：
2.9
作者：
Fabiilli,MarioL;Phanse,RahulA;Moncion,Alexander;Fowlkes,JBrian;Franceschi,RennyT
通讯作者：
Franceschi,RennyT

In Situ Transfection by Controlled Release of Lipoplexes Using Acoustic Droplet Vaporization.

DOI：
10.1002/adhm.201600008
发表时间：
2016-07
期刊：
Advanced healthcare materials
影响因子：
10
作者：
Juliar BA;Bromley MM;Moncion A;Jones DC;O'Neill EG;Wilson CG;Franceschi RT;Fabiilli ML
通讯作者：
Fabiilli ML

Controlled release of basic fibroblast growth factor for angiogenesis using acoustically-responsive scaffolds.

DOI：
10.1016/j.biomaterials.2017.06.012
发表时间：
2017-09
期刊：
Biomaterials
影响因子：
14
作者：
Moncion A;Lin M;O'Neill EG;Franceschi RT;Kripfgans OD;Putnam AJ;Fabiilli ML
通讯作者：
Fabiilli ML

In vitro and in vivo assessment of controlled release and degradation of acoustically responsive scaffolds.

DOI：
10.1016/j.actbio.2016.09.026
发表时间：
2016-12
期刊：
ACTA BIOMATERIALIA
影响因子：
9.7
作者：
Moncion, Alexander;Arlotta, Keith J.;O'Neill, Eric G.;Lin, Melissa;Mohr, Lily A.;Franceschi, Renny T.;Kripfgans, Oliver D.;Putnam, Andrew J.;Fabiilli, Mario L.
通讯作者：
Fabiilli, Mario L.