Project ID BE-MI2024_19


Co Supervisor 1A Faculty of Dentistry, Oral & Craniofacial Sciences,Centre for Craniofacial & Regenerative BiologyWebsite

Co Supervisor 1B Faculty of Dentistry, Oral & Craniofacial Sciences, Centre for Oral, Clinical & Translational SciencesWebsite

Development of fibre-optic depth selective molecular assessment of dentoalveolar bone grafts

The clinical success of alveolar bone regeneration using implants is typically determined using radiography or visually by the surgeon. This has major limitations as neither of these approaches offer insights into the integrity and tissue formation at the molecular level. Minimally invasive light-based molecular monitoring of grafted sites over time without the need for ionising radiation could provide a unique way to obtain information on tissue integrity and enable early detection of critical changes. Raman spectroscopy is a label-free non-invasive optical technique that can probe the structure and composition of tissues and materials at the molecular level. Here we will develop and validate a novel depth selective fibre-optic Raman technique for oral bone graft assessment. The specific aims have been designed to meet the unmet clinical needs including development of Raman technology, validation of the prototype and if successful, application in patients.

The student will learn transferable skills in biomedical engineering, biophotonics, data analysis/deep learning and acquire knowledge in how to innovate in translational sciences.

The overarching objectives for the project are as follows:

Aim 1 (year 1): Development of a Bessel beam-enabled fibre-optic Raman probe for depth selective tissue analysis. The student will create a prototype and data analysis pipeline

Aim 2 (year 2): Molecular analysis of bone grafts in bulk tissues ex vivo using deep learning. The student will apply the developed prototype to tissue phantom models and bulk tissues to analyse embedded biomaterials

Aim 3 (year 3): Application of depth selective Raman spectroscopy for minimally-invasive monitoring of grafted sites over time in patients. The student will collect a database of Raman spectra from patients and validate the developed technique

Representative Publications

1. ‘Raman needle arthroscopy for in vivo molecular assessment of cartilage, Kimberly R. Kroupa, Man I Wu, Juncheng Zhang, Magnus Jensen, Wei Wong, Julie B. Engiles, Mark W. Grinstaff, Brian D. Snyder, Mads S. Bergholt, Michael B. Albro, Journal of Orthopaedic Research, 2021;1-11, DOI: 10.1002/jor.25155

2. Multiplexed polarized hypodermic Raman needle probe for biostructural analysis of articular cartilage, Magnus Jensen, Conor C. Horgan, Tom Vercauteren, Michael B. Albro, and Mads S. Bergholt, Optics Letters, Vol. 45, Issue 10, pp. 2890-2893 (2020), DOI: 10.1364/OL.390998

3. Fiber-optic confocal Raman spectroscopy for real-time in vivo diagnosis of dysplasia in Barrett’s esophagus M. S. Bergholt, W. Zheng, K. Y. Ho, M. Teh, K. G. Yeoh, J. B. Y. So, A. Shabbir, Z. Huang, Gastroenterology, 146(1), 27-32, 2014, DOI: 10.1053/j.gastro.2013.11.002

1. Addressing uncertainties in correlative imaging of exogenous particles with the tissue microanatomy with synchronous imaging strategies. Morrell AP, Martin RA, Roberts HM, Castillo-Michel H, Mosselmans JFW, Geraki K, Warfield AT, Lingor P, Qayyum W, Graf D, Febbraio M, Addison O. Metallomics. 2023;15(6) doi: 10.1093/mtomcs/mfad030.

2. Origin of micro-scale heterogeneity in polymerisation of photo-activated resin composites. Sirovica S, Solheim JH, Skoda MWA, Hirschmugl CJ, Mattson EC, Aboualizadeh E, Guo Y, Chen X, Kohler A, Romanyk DL, Rosendahl SM, Morsch S, Martin RA, Addison O. Nat Commun. 2020 Apr 15;11(1):1849. doi: 10.1038/s41467-020-15669-z.

3. Interconnectivity explains high canalicular network robustness between neighboring osteocyte lacunae in human bone. Bortel, E., Grover, L., Eisenstein, N., Seim, C., Suhonen, H., Pacureanu, A., Westenberger, P., Raum, K., Langer, M., Peyrin, F., Addison, O#., & Hesse, B#. Advanced NanoBiomed Research, 2022, 2100090.