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Inhibition vs. promotion of intrafibrillar mineralization of collagen fibrils

Award Number: R21DE035693
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: 08/06/2026
PERIOD OF PERFORMANCE END DATE: 08/05/2028

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Inhibition vs. promotion of intrafibrillar mineralization of collagen fibrils - Abstract The prevailing belief that calcium and phosphate ions are directly extracted from saturated solutions to form minerals appears to be incorrect in the context of biomineralization. Recent in vitro evidence suggests that these ions are instead captured by specific proteins from the solution, maintained at high concentrations in the form of liquid-like nanodroplets, and then delivered to mineralization sites on structural protein assemblies. Here, they solidify as amorphous minerals through a process known as the Polymer-Induced Liquid Precursor (PILP) pathway. It is well understood that mineralized tissues evolved in environments that inhibit mineral formation. Typically, body fluids are saturated solutions that would precipitate minerals like apatite or calcite if not for the presence of mineral inhibitors. Acidic and anionic domains in proteins, such as Matrix-Gla Protein in blood serum and proteoglycans in the periodontal ligament, play a crucial role in calcium sequestration and maintaining solution stability. Biomineralization, the process by which minerals are induced to form in tissue for weight- bearing, mastication, or protection, evolved in these inhibitory environments through a series of gene modifications and primarily through post-translational modifications to proteins. Consequently, proteins involved in mineralization in the extracellular matrices of bone and dentin are characterized by extended domains of successive acidic and phosphorylated residues. Despite the PILP method’s substantial success in mineralizing collagen and remineralizing dentinal and osseous tissues in numerous in vitro studies over the past 15 years, the translation of this potentially impactful method into clinical practice has not yet been achieved. Research on the mechanisms of the PILP method has largely focused on the forces driving the infiltration of calcium and phosphate ions into collagen fibrils. However, the significance of inhibitory molecules has not been thoroughly explored, resulting in an incomplete mechanistic understanding of the native collagen mineralization process in vivo. Therefore, we hypothesize that examining the influence of mineralization inhibitors on the PILP-induced mineralization process is critical for mimicking collagen fibril mineralization in vitro and for understanding the mechanisms that can impair collagen fibril mineralization both in vitro and in vivo.


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 = $451,000 )
2026	2026	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Oral Diseases and Disorders Research	000	1	8/7/2026	NEW	$451,000
														Subtotal = $451,000

Grand Total All Awards = $451,000

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Inhibition vs. promotion of intrafibrillar mineralization of collagen fibrils

Award Number: R21DE035693

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: 08/06/2026

PERIOD OF PERFORMANCE END DATE: 08/05/2028

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