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Multi-Scale In Vitro 3D Tissue Model of Vascularized Bone-Cartilage Interactions

Award Number: R44AR072169
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Abstract Current in vitro models of vascularized bone tissues do not mimic the in vivo microenvironment comprising of diverse cell types in communication with each other through stromal barriers. In addition, they are hampered by lack of real-time visualization and quantitation of vasculature- bone as well as bone-cartilage interactions. In contrast, animal models while providing useful information are time consuming, expensive and in recent years, have increasingly raised ethical concerns. Furthermore, animal studies provide limited understanding of mechanistic behavior compared to well-controlled in vitro studies. Thus, there is an unmet need for an in vitro platform for improved monitoring and analysis of vascularized bone-cartilage interactions. In Phase I we successfully developed and demonstrated a multi-scale in vitro model comprising of a micro scale microfluidic device and a meso scale bioreactor to mimic the in vivo conditions. We successfully differentiated in the platform patient derived human mesenchymal stem cells (hMSCs) towards osteogenic and chondrogenic lineages highlighting interactions with vascular endothelial cells. Following detailed functional characterizations, we demonstrated the capability of the platform to evaluate functionality for an anti-inflammatory therapeutic. In Phase II we will test additional pro-inflammatory components that mimic the native osteochondral microenvironment. We will also use our multi-scale system for (a) mechanistic understanding and (b) therapeutic screening of candidate treatments following inflammatory insults. Finally, we will develop the infrastructure to increase the throughput capability by multiplexing the platform for automation. A multi-disciplinary industry-academic partnership with expertise in microfluidics cell-based assays and musculoskeletal biology and tissue regeneration has been assembled for successful completion of this project. By providing an accurate, quantitative and predictive model of physiological interactions, the developed multi-scale platform promises to establish a new paradigm for in vitro assessment of the physiological response to therapeutics.


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: 2023 ( Subtotal = $0 )
2023	2022	CFD RESEARCH CORPORATION	6820 MOQUIN DR NW	HUNTSVILLE	AL	35806	MADISON	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	8/16/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $836,797 )
2022	2022	CFD RESEARCH CORPORATION	6820 MOQUIN DR NW	HUNTSVILLE	AL	35806	MADISON	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	9/2/2022	NON-COMPETING CONTINUATION	$836,797
														Subtotal = $836,797

Issue Date FY: 2021 ( Subtotal = $893,953 )
2021	2021	CFD RESEARCH CORPORATION	6820 MOQUIN DR NW	HUNTSVILLE	AL	35806	MADISON	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	9/24/2021	COMPETING CONTINUATION	$893,953
														Subtotal = $893,953

Grand Total All Awards = $1,730,750

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Multi-Scale In Vitro 3D Tissue Model of Vascularized Bone-Cartilage Interactions

Award Number: R44AR072169

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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