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Exosome-mediated Craniofacial Bone Tissue Engineering by Controlled Release

Award Number: F30DE029359
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 05/01/2020
PERIOD OF PERFORMANCE END DATE: 05/10/2024

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Exosome-mediated Craniofacial Bone Tissue Engineering by Controlled Release - Abstract Healthy bone is critically important to systemic health. Of relevance to the craniofacial complex, dental implants require that empty sockets are filled with bone prior to implant placement and restoring dentition. Bone quality and bone amount are strongly correlated with both the short- and long-term success of dental implants. Biomaterials-based bone regeneration is promising to circumvent shortcomings of bone grafting. These biomaterials can be functionalized with instructive components which guide tissue regeneration. Exosomes, thought to be nature's endogenous biomolecule delivery platform, are particularly interesting because of their innate biocompatibility and capacity to communicate with cells to modulate their phenotype. Recent in vitro data suggests that exosomes derived from mineralizing MC3T3 pre-osteoblasts are able to induce mineralization in naive bone marrow stromal cells. However, engineering a means for their efficient therapeutic delivery in vivo, in a clinically and biologically relevant manner is a challenge in exosome-mediated therapy. The overall therapeutic goal of this project is to exploit the regenerative capacity of endogenous mesenchymal stem cells by mimicking the natural secretion of exosomes with a polymeric tissue engineering construct. My preliminary data suggests that polymeric self-assembly via a tunable biodegradable copolymer can encapsulate exosomes, which are released in a sustained fashion over time. My central hypothesis is that controlled release of osteogenic exosomes from a polymer matrix will promote craniofacial bone healing. The specific aims are to 1) develop a well-controlled fabrication method which allows incorporation of an exosome-releasing modality into a three-dimensional tissue engineering construct; 2) evaluate the integrity of the bioactive exosome contents during encapsulation and release, and their ability to cause phenotype changes in downstream cells; and 3) validate the technology invented herein in two in vivo models of craniofacial bone regeneration. The outcomes of the proposed experiments will demonstrate a means for the encapsulation and controlled delivery of exosomes from a polymer matrix, causing craniofacial bone regeneration without stem cell transplantation. Effective exosome encapsulation and release strategies, which preserve their biologic activity, are critical to advancing the field of exosome-mediated clinical therapies, which can be applied to the regeneration of many tissue types.


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: 2025 ( Subtotal = -$30,615 )
2025	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Oral Diseases and Disorders Research	001	5	3/25/2025	NON-COMPETING CONTINUATION	-$800
2025	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Oral Diseases and Disorders Research	000	5	12/6/2024	NON-COMPETING CONTINUATION	-$29,815
														Subtotal = -$30,615

Issue Date FY: 2024 ( Subtotal = $52,074 )
2024	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Oral Diseases and Disorders Research	001	5	6/19/2024	NON-COMPETING CONTINUATION	$1,280
2024	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Oral Diseases and Disorders Research	000	5	4/15/2024	NON-COMPETING CONTINUATION	$50,794
														Subtotal = $52,074

Issue Date FY: 2023 ( Subtotal = $53,494 )
2023	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON STREET	ANN ARBOR	MI	48109	WASHTENAW	USA	Oral Diseases and Disorders Research	000	4	3/7/2023	NON-COMPETING CONTINUATION	$53,494
														Subtotal = $53,494

Issue Date FY: 2022 ( Subtotal = $52,552 )
2022	2022	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Oral Diseases and Disorders Research	000	3	3/17/2022	NON-COMPETING CONTINUATION	$51,836
2022	2022	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Oral Diseases and Disorders Research	001	3	4/20/2022	NON-COMPETING CONTINUATION	$717
2022	2022	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Oral Diseases and Disorders Research	002	3	5/25/2022	NON-COMPETING CONTINUATION	-$1
														Subtotal = $52,552

Issue Date FY: 2021 ( Subtotal = $51,836 )
2021	2021	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Oral Diseases and Disorders Research	000	2	3/16/2021	NON-COMPETING CONTINUATION	$51,836
														Subtotal = $51,836

Issue Date FY: 2020 ( Subtotal = $51,320 )
2020	2020	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Oral Diseases and Disorders Research	000	1	11/29/2019	NEW	$50,816
2020	2020	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Oral Diseases and Disorders Research	002	1	2/12/2020	NEW	$0
2020	2020	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Oral Diseases and Disorders Research	001	1	2/12/2020	NEW	$504
														Subtotal = $51,320

Grand Total All Awards = $230,661

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Exosome-mediated Craniofacial Bone Tissue Engineering by Controlled Release

Award Number: F30DE029359

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 05/01/2020

PERIOD OF PERFORMANCE END DATE: 05/10/2024

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