loading
loading
NIH grant 1R21DE035693-01A1: Inhibition vs. promotion of intrafibrillar mineralization of collagen fibrils
Institute: {'code': 'DE', 'abbreviation': 'NIDCR', 'name': 'National Institute of Dental and Craniofacial Research', 'admin_org_id': '12500070', 'admin_funding_url': ''}. PI: Stefan Friedrich Habelitz. Award: $451000.
Start: 2026-08-06T00:00:00.
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.document fetched 2026-08-16 06:34