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Microfabrication-based Biomimetic Approach for In Vitro Red Blood Cell Maturation

Award Number: R41HL138184
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/20/2017
PERIOD OF PERFORMANCE END DATE: 07/19/2019

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Microfabrication-based Biomimetic Approach for In Vitro Red Blood Cell Maturation - Abstract The overall goal of this proposal is to develop systems for efficient ex vivo maturation of functional human red blood cells (RBCs), which holds tremendous potential for addressing supply bottlenecks for delivering new therapeutic options to chronically transfused patients with severe alloimmunization and for novel strategies for delivering therapeutics via engineered RBCs. No approaches developed so far have shown the ability to produce both enucleated and mature RBCs that have reliable shelf-life in storage or viability upon transfusion. Our hypothesis is that in existing culture systems, late stage erythroblasts/early reticulocytes lose too much surface area during enucleation and membrane remodeling, leading to more spherical cells that are susceptible to hemolysis. We propose a biomimetic approach wherein cells are passed through microslit filters to recapitulate in vivo mechanical deformations that appropriately constrain cell area/volume, promote proper biconcave disc morphology and limit potentially harmful extensional stretching. This proposal brings together expertise in microfabrication at SiMPore Inc. with RBC biology and rheology at the University of Rochester. SiMPore will optimize micro-slit manufacturing methods and integrate microslit filter membranes into fluidic systems for RBC maturation testing at Rochester (Aim 1). Similar efforts will be carried out to test the capability of microslit filters to separate and concentrate mature/enucleated RBCs from nucleated precursors (Aim 2). Relevant experts will guide developing regulatory and commercialization plans so that the team is positioned to carry out clinical studies during Phase II. The developed RBC maturation tools can be married with existing large volume bioreactors for RBC precursor expansion so that final maturation using this approach can be scaled for practical volumes.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2017	SIMPORE INC.	150 LUCIUS GORDON DR STE 110	WEST HENRIETTA	NY	14586	MONROE	USA	Blood Diseases and Resources Research	000	1	1/14/2020	NEW	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $225,000 )
2017	2017	SIMPORE INC.	150 LUCIUS GORDON DR STE 119	WEST HENRIETTA	NY	14586	MONROE	USA	Blood Diseases and Resources Research	000	1	7/20/2017	NEW	$225,000
														Subtotal = $225,000

Grand Total All Awards = $225,000

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Microfabrication-based Biomimetic Approach for In Vitro Red Blood Cell Maturation

Award Number: R41HL138184

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/20/2017

PERIOD OF PERFORMANCE END DATE: 07/19/2019

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