Novel Pre-Vascularized Scaffolds for Personalized Myocardial Repair
Description: The inability to administer sufficient oxygen in a controlled and sustained fashion into thick cardiovascular tissues has attracted a growing interest towards the design and development of new functional biomaterials. An emerging class of biomaterials to address this medical need is oxygen-releasing substances. We aim to develop a 3D functional scaffold that can release oxygen on demand to overcome mass transport limitations in conventional tissue constructs. While there are a number approaches to provide oxygen in engineered scaffolds, these methods present short-lived effects, cannot control oxygen-release kinetics, and difficult to fabricate. To accomplish our goal, we propose three aims. In Aim 1, we will synthesize oxygen-releasing materials encapsulated in a hydrophobic polymer within a hydrogel matrix and characterize the release kinetics of oxygen under hypoxia and normoxia. We will characterize the release kinetics of oxygen by controlling material properties. In Aim 2, we will evaluate the cellular compatibility of the oxygen-releasing scaffolds by viability, adhesion, proliferation, metabolic activity, and functionality assays. In Aim 3, we will fabricate a 3D vascularized tissue model using oxygen-releasing materials by a co-culture strategy including cardiomyocytes and endothelial cells, and assess the functionality of these 3D constructs. The metrics that will be used to measure the outcomes of the aims include i) the rate at which oxygen is released, ii) the concentration of oxygen in the growth medium, iii) swelling, degradation, porosity, and mechanical properties of the oxygen-releasing constructs, iv) cell growth and metabolism, v) cell death (apoptosis, necrosis, caspase 9 activity, LDH release), vi) cell function (beating, phenotypic marker expression), and vii) the extent of vascularization (formation of vascular networks, size of lumens, distribution of lumens, number of branches). The oxygen-releasing biomaterials represent a first step towards fabrication of functional cardiovascular tissues with a well-connected blood supply. The ability to prevent the onset of hypoxia makes these materials invaluable for regeneration of highly vascularized tissues including the heart muscle. These biomaterials will inspire the development of fully viable cardiac patches that survive up to three weeks and are able to remodel at clinically relevant sizes helping translate bench protocols to the bedside.
Funder: American Heart Association
Amount: $300,000
Funding type: research
Funder scheme: Transformational Project Award
Start date: 2019-07-01
End date: 2022-06-30
Investigators: Gulden Camci-unal, Gulden Camci-unal
Institution: University of Massachusetts Lowell
Funded outputs count: 5
Funder award ID: 19TPA34910111
OpenAlex ID: G4600155264