Thursday, July 3, 2025 7/3/2025

Microribbon scaffold-mediated Immunomodulation for Cranial Bone Repair

Award Number: R01DE024772
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2015
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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Microribbon scaffold-mediated Immunomodulation for Cranial Bone Repair - Bone healing involves sequential and overlapping biological processes including inflammation, new bone formation and remodeling. Most bone tissue engineering research to date focused on targeting bone-forming cells such as stem cells. Emerging studies highlight the critical roles of immune cells in fracture healing. Macrophages (M𝜙) is one of the first responders to bone defects and can be polarized into pro-inflammatory M1 and pro-regenerative M2 phenotype. Unsolved acute inflammatory phase and delayed M1 to M2 phenotype switch often lead to long-term and chronic inflammation, resulting in delayed bone healing. To enhance bone healing, there remains a lack of strategy that promotes desirable M𝜙 polarization at appropriate timing. Biomaterial scaffolds have been widely used for bone tissue engineering as carriers for cell and growth factors delivery. Recent studies also demonstrate biomaterials compositions impact immune responses, with natural extracellular derived materials promote more pro-regenerative immune response than synthetic materials. However, several key gaps in knowledge remain. First, previous studies were done using soft-tissue defect models only, and how varying biomaterials compositions impact bone healing remains unknown. Second, macroporosity is critical for bone regeneration in vivo, whereas previous work on assessing immune response to biomaterials is limited to conventional nanoporous hydrogels. Third, previous work on the role of T cells in bone healing is limited to a non-critical size long bone fracture model, and no scaffolds were used. T-cell response to scaffold implant in a critical-sized cranial defect model has never been studied before. Last, previous work only studied individual cell type (i.e. immune cell only or stem cell only), yet how biomaterials composition modulates cell-cell crosstalk and subsequent tissue regeneration remains largely unknown. The goal of our original R01 was to assess the potential of µRB scaffolds for enhancing stem cell-based tissue regeneration by focusing on stem cell differentiation. The goal of this renewal R01 application is to harness µRB scaffolds to enhance bone formation through immunomodulation by tuning biomaterial composition, which has never been investigated before. Specifically, we propose to (1) Assess the effect of varying µRB scaffold composition on M𝜙 polarization and osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro; (2) Investigate the effect of the varying µRB composition on MSC/M𝜙 crosstalk, and further impacts on MSC-based bone formation and T cell response using a 3D co-culture model in vitro; and (3) Evaluate the effect of the varying µRB scaffold composition on immune responses and bone regeneration in vivo using a mouse critical-size cranial defect model. By working at the interface of biomaterials, immunology, bone disease and biology, stem cells, animal models, and high dimensional single cell analyses, the proposed work will fill in the critical gap of knowledge on the divergent immune response to macroporous scaffolds with tunable compositions and guide optimal scaffold design to enhance critical-size cranial bone repair through immunomodulation.


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 = $541,219 )
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Oral Diseases and Disorders Research	000	10	5/8/2025	NON-COMPETING CONTINUATION	$541,219
														Subtotal = $541,219

Issue Date FY: 2024 ( Subtotal = $529,076 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Oral Diseases and Disorders Research	000	9	5/31/2024	NON-COMPETING CONTINUATION	$529,076
														Subtotal = $529,076

Issue Date FY: 2023 ( Subtotal = $536,209 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Oral Diseases and Disorders Research	000	8	6/7/2023	NON-COMPETING CONTINUATION	$536,209
														Subtotal = $536,209

Issue Date FY: 2022 ( Subtotal = $485,308 )
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Oral Diseases and Disorders Research	000	7	5/18/2022	NON-COMPETING CONTINUATION	$485,308
														Subtotal = $485,308

Issue Date FY: 2021 ( Subtotal = $489,808 )
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Oral Diseases and Disorders Research	001	6	7/15/2021	COMPETING CONTINUATION	$490,208
2021	2019	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Oral Diseases and Disorders Research	000	5	5/21/2021	NON-COMPETING CONTINUATION	-$400
														Subtotal = $489,808

Issue Date FY: 2019 ( Subtotal = $401,519 )
2019	2019	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Oral Diseases and Disorders Research	000	5	12/20/2018	NON-COMPETING CONTINUATION	$401,519
														Subtotal = $401,519

Issue Date FY: 2018 ( Subtotal = $401,376 )
2018	2018	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Oral Diseases and Disorders Research	001	4	4/24/2018	NON-COMPETING CONTINUATION	$40,138
2018	2018	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Oral Diseases and Disorders Research	000	4	1/25/2018	NON-COMPETING CONTINUATION	$361,238
														Subtotal = $401,376

Issue Date FY: 2017 ( Subtotal = $401,309 )
2017	2017	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Oral Diseases and Disorders Research	000	3	1/23/2017	NON-COMPETING CONTINUATION	$361,177
2017	2017	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Oral Diseases and Disorders Research	001	3	5/26/2017	NON-COMPETING CONTINUATION	$40,132
														Subtotal = $401,309

Issue Date FY: 2016 ( Subtotal = $401,250 )
2016	2016	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Oral Diseases and Disorders Research	001	2	5/31/2016	NON-COMPETING CONTINUATION	$401,250
2016	2015	STANFORD UNIVERSITY	616 SERRA STREET	STANFORD	CA	943056215	SANTA CLARA	USA	Oral Diseases and Disorders Research	000	1	3/16/2016	NEW	$0
														Subtotal = $401,250

Issue Date FY: 2015 ( Subtotal = $401,250 )
2015	2015	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Oral Diseases and Disorders Research	000	1	12/8/2014	NEW	$401,250
														Subtotal = $401,250

Grand Total All Awards = $4,588,324

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Microribbon scaffold-mediated Immunomodulation for Cranial Bone Repair

Award Number: R01DE024772

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/01/2015

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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