Towards bone regeneration: Understanding the nucleating ability of proline-rich peptides in biomineralisation.

Autor: Øvrebø Ø; Department of Biomaterials, Institute of Clinical Dentistry, University of Oslo, 0318 Oslo, Norway; Department of Chemistry, Materials and Chemical Engineering 'Giulio Natta', Politecnico di Milano, 20133 Milano, Italy; Material Biomimetic AS, Oslo Science Park, 0349 Oslo, Norway., De Lauretis A; Department of Biomaterials, Institute of Clinical Dentistry, University of Oslo, 0318 Oslo, Norway; Department of Chemistry, Materials and Chemical Engineering 'Giulio Natta', Politecnico di Milano, 20133 Milano, Italy., Ma Q; Department of Biomaterials, Institute of Clinical Dentistry, University of Oslo, 0318 Oslo, Norway., Lyngstadaas SP; Department of Biomaterials, Institute of Clinical Dentistry, University of Oslo, 0318 Oslo, Norway., Perale G; Industrie Biomediche Insubri SA, Mezzovico-Vira 6805, Switzerland; Faculty of Biomedical Sciences, University of Southern Switzerland, Lugano 6900, Switzerland; Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Donaueschingenstrasse 13, 1200 Vienna, Austria., Nilsen O; Centre for Materials Science and Nanotechnology, Department of Chemistry, University of Oslo, Gaustadalléen 21, NO-0349 Oslo, Norway., Rossi F; Department of Chemistry, Materials and Chemical Engineering 'Giulio Natta', Politecnico di Milano, 20133 Milano, Italy., Haugen HJ; Department of Biomaterials, Institute of Clinical Dentistry, University of Oslo, 0318 Oslo, Norway. Electronic address: h.j.haugen@odont.uio.no.
Jazyk: angličtina
Zdroj: Biomaterials advances [Biomater Adv] 2024 May; Vol. 159, pp. 213801. Date of Electronic Publication: 2024 Feb 21.
DOI: 10.1016/j.bioadv.2024.213801
Abstrakt: Obtaining rapid mineralisation is a challenge in current bone graft materials, which has been attributed to the difficulty of guiding the biological processes towards osteogenesis. Amelogenin, a key protein in enamel formation, inspired the design of two intrinsically disordered peptides (P2 and P6) that enhance in vivo bone formation, but the process is not fully understood. In this study, we have elucidated the mechanism by which these peptides induce improved mineralisation. Our molecular dynamics analysis demonstrated that in an aqueous environment, P2 and P6 fold to interact with the surrounding Ca 2+ , PO 4 3- and OH - ions, which can lead to apatite nucleation. Although P2 has a less stable backbone, it folds to a stable structure that allows for the nucleation of larger calcium phosphate aggregates than P6. These results were validated experimentally in a concentrated simulated body fluid solution, where the peptide solutions accelerated the mineralisation process compared to the control and yielded mineral structures mimicking the amorphous calcium phosphate crystals that can be found in lamella bone. A pH drop for the peptide groups suggests depletion of calcium and phosphate, a prerequisite for intrinsic osteoinduction, while S/TEM and SEM suggested that the peptide regulated the mineral nucleation into lamella flakes. Evidently, the peptides accelerate and guide mineral formation, elucidating the mechanism for how these peptides can improve the efficacy of P2 or P6 containing devices for bone regeneration. The work also demonstrates how experimental mineralisation study coupled with molecular dynamics is a valid method for understanding and predicting in vivo performance prior to animal trials.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare no financial and personal relationships with other people or organisations that could inappropriately influence bias to this work. IPR rights of the consensus peptides (US Patent US8367602B2 and connected titles) belong to Industrie Biomediche Insubri SA (Switzerland), where Giuseppe Perale is a founding shareholder and the executive vice president. The patent related to the consensus peptides was invented by Ståle Petter Lyngstadaas but has since been sold to Industrie Biomediche Insubri SA. NuPep AS, owned solely by Øystein Øvrebø, has a licencing right to the consensus peptides IPR above.
(Published by Elsevier B.V.)
Databáze: MEDLINE
Externí odkaz: