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Biomimetic and Injectable Highly Porous Nanofiber Microsphere-based Platform for Alveolar Bone Regeneration

Award Number: R01DE031272
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: 06/08/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2028

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Biomimetic and Injectable Highly Porous Nanofiber Microsphere-based Platform for Alveolar Bone Regeneration - PROJECT SUMMARY Alveolar bone is a critical tissue for tooth and dental implant retention. Increasing alveolar bone mass in patients who lose this tissue as a result of periodontal disease or trauma is crucial for successful dental implant therapy (e.g., loss of bone around a tooth extraction site prior to implant placement). Currently, bone grafts (e.g., iliac or mandibular bone) or artificial bone grafts are commonly used for alveolar bone regeneration therapy. However, most of these therapies require extensive surgical procedures, which present risks of many complications, particularly in aged patients. Therefore, the development of new alveolar bone regeneration techniques that do not require surgical procedures is urgently needed. Herein, in this proposed study, we aim to develop an injectable and biomimetic highly porous nanofiber microsphere-based therapy for healing critical- sized alveolar bone defects. We recently developed an exciting approach for the fabrication of biomimetic nanofiber microspheres consisting of short electrospun nanofiber segments without limitation to certain compositions. Cells can attach and proliferate on the surface of such nanofiber microspheres. Working with Dr. Reinhardt (Co-I), we also demonstrated that mineralized short nanofibers incorporated with E7-BMP-2 peptides showed promise for healing a critical-sized socket defect model created in rat maxillae, following extraction of the first molar teeth. In addition, our most recent study revealed that BMP-2/QK peptides conjugated nanofiber microspheres can significantly enhance osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and tubular network formation of human umbilical vein endothelial cells (HUVECs). Based on these findings, it is hypothesized that the injectable highly porous nanofiber microspheres in combination with biomimetic delivery of signaling molecules and/or incorporation of BMSCs could greatly promote alveolar bone regeneration after minimally invasive administration to critical-sized alveolar bone defects in rats. To test the hypothesis and accomplish the primary objective, our strategy is three-fold: i) Demonstrate the fabrication of porous nanofiber microspheres with controlled composition, structure, and coupling of signaling molecules; ii) Examine the effect of engineered porous nanofiber microspheres with biomimetic delivery of signaling molecules on cellular response; and iii) Determine the bone regenerative capacity of injectable porous nanofiber microspheres in combination with biomimetic delivery of signaling molecules and/or BMSCs for healing alveolar bone defects in rats. We expect to identify the critical factors of biomimetic and injectable highly porous nanofiber microsphere-based therapy that contribute to alveolar bone regeneration. Also, we expect successful completion of these aims to lay the foundation for developing injectable bone grafts that could greatly accelerate healing of alveolar bone defects without invasive surgical procedures.


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: 2026 ( Subtotal = $511,798 )
2026	2026	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	4215 EMILE ST	OMAHA	NE	68105	DOUGLAS	USA	Oral Diseases and Disorders Research	000	4	3/6/2026	NON-COMPETING CONTINUATION	$511,798
														Subtotal = $511,798

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	4215 EMILE ST	OMAHA	NE	68105	DOUGLAS	USA	Oral Diseases and Disorders Research	000	3	3/25/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $530,145 )
2024	2024	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Oral Diseases and Disorders Research	000	3	3/27/2024	NON-COMPETING CONTINUATION	$486,868
2024	2024	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Oral Diseases and Disorders Research	001	3	6/10/2024	NON-COMPETING CONTINUATION	$43,277
														Subtotal = $530,145

Issue Date FY: 2023 ( Subtotal = $533,672 )
2023	2023	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Oral Diseases and Disorders Research	000	2	2/28/2023	NON-COMPETING CONTINUATION	$533,672
														Subtotal = $533,672

Issue Date FY: 2022 ( Subtotal = $470,967 )
2022	2022	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Oral Diseases and Disorders Research	000	1	6/8/2022	NEW	$470,967
														Subtotal = $470,967

Grand Total All Awards = $2,046,582

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Biomimetic and Injectable Highly Porous Nanofiber Microsphere-based Platform for Alveolar Bone Regeneration

Award Number: R01DE031272

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: 06/08/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2028

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