AO CMF BOOST Clinical Priority Program

Translational approaches for bone constructs: their impact on facial bone reconstruction
AO CMF BOOST

Pillars of the AO CMF BOOST—Clinical Priority Program

Consortium materials:

  •  Self assembling Hydrogel (Soft)

    • Regulated endogenous factor presentation

  • Calcined (heat treated) bone (Hard)

    • Particles to improve flat bone healing

    • Blocks for larger defects e.g. Mandible

  • Flat bone approach 

    • Gel Sheets patterned with bone particles

  • Bulk defects (e.g. Mandible)

    • Patient specific bone blocks impregnated with gel

Cellularized intraoperatively with bone marrow aspirate concentrate (BMAC) / fibrin.

Final product: Off the shelf, patient specific, autologous, flexible approach.

  • Materials_for_bone_regeneration.png

Background:
Immune response coordinates and regulates normal healing 
In vitro tests lack immunological investigations

Consortium aims:
Monitor
Develop  in vitro immunological testing platform to predict in vivo behavior
Establish molecular markers/ screening platform for adverse immunological responses

Control
Regulate immune response using interleukin binding peptides
Eliminate foreign body reactions

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ScreeningProof of concept
Immunological reactionsIntramembranous healing
Mechanism of actionEndochondral / bulk healing

 

Background:
Understanding of mechanism of action increases potential success of regulatory approval.

Consortium Aims:
Single cell sequencing to establish osteogenesis pathway

Single cell sequencing to interrogate immune response

 Modifying effect of mechanical stimulation for mandible regeneration

  • In vitro bioreactors

Iterative approach to inform material design.

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Background:
Many materials show in vitro promise yet fail in vivo
Current classical testing process established decades ago

Consortium aims:
Earlier in vivo tests “fail fast”
Focus optimization on promising compositions
Changing the face of osteogenic material testing

 

AOC_Research-BOOST-Material-testing.png

Consortium aims to enhance performance of Fibrin, BMAC and bone void fillers. Both are currently clinically available 

AO Course Lectures: 

  • Fibrin/ BMAC use
  • Bone fillers
  • Potential for enhancement of clinically available therapies

Outcomes

 

 

  1. Ligorio C., Tavasoli E., Karaman-Jurukovska N., Ittycheri A., Wu Y., Kotowska A.M, Scurr D.J., Gupta S.A., Moogan L.V., Emmetsberger J., Lu F., German G.K., Mata A., Mammone T. (2024). Non-Invasive Monitoring of Palmitoyl Hexapeptide-12 Interaction with Human Skin Layers and Its Cosmetic Skincare Benefits. ACS Applied Bio Materials (Accepted).
  2. Padilla-Lopategui S*., Ligorio C*., Bu W., Laurenza D., Redondo-Gomez R., Owens R., Iskratsch T., Sun H., Rose F., Mata A. (2024). Biocooperative regenerative materials by harnessing blood-clotting and peptide self-assembly. Advanced Materials, 2407156. https://doi.org/10.1002/adma.202407156. *Equal contribution.
  3. Ligorio C., Martinez Espuga M., Laurenza D., Hartley A., Rodgers C.B., Kotowska A.M., Scurr D.J., Dalby M.J., Ordóñez-Morán P., Mata A. (2024). Disassembly of Self-Assembling Peptide Hydrogels as a Versatile Method for Cell Extraction and Manipulation. J Materials Chemistry B, 12, 11939-11952, https://doi.org/10.1039/D4TB01575D.
  4. Murphy J.F., Lavelle M., Asciak L., Burdis R., Levis H., Ligorio C., McGuire J., Polleres M., Smith P., Tullie L., Uribe-Gomez J., Chen B., Dawson J., Gautrot J., Hooper N., Kelly D., Li V., Mata A., Pandit A., Phillips J., Shu W., Stevens M., Williams R., Armstrong J., Huang Y.Y.S. (2024). Biofabrication and Biomanufacturing in Ireland and the UK - Frontier Research for Industry 4.0. Bio-Design and Manufacturing 7(6), 825-856 https://doi.org/10.1007/s42242-024-00316-z.
  5. Ligorio C., Kotowska A., Scurr D.J., Tavasoli E., Karaman-Jurukovska N., Mata A., Moogan L., German G., Lu F., Mammone T. (2024). 084 Cosmetic peptide penetration and assembly in human skin: A label-free approach, Journal of Investigative Dermatology, 144, 8, Supplement. https://doi.org/10.1016/j.jid.2024.06.100.
  6. Watts J.A., Ligorio C., Mata A., Fay M.W. Direct detection camera as an alternative to negative staining for peptide structure determination. Proceedings of the Microscience Microscopy Congress 2023, incorporating EMAG 2023. www.doi.org/10.22443/rms.mmc2023.238.
  7. Ligorio C., Mata A. (2023). Synthetic extracellular matrices with function-encoding peptides, Nature Reviews Bioengineering, 1:518–536. https://doi.org/10.1038/s44222-023-00055-3. 

 

The Team

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Consortium Team

4 Institutes, 1 Goal
Profile page
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Prof. Martin Stoddart, PhD

AO Research Institute Davos, Coordinator
Institute page
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Prof Cezmi A. Akdis, MD, PhD

Swiss Institute of Allergy and Asthma Research (SIAF), Co-PI
University page
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Prof. Alvaro Mata, D.Eng

University of Nottingham, Co-PI
Profile page
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Prof. Zhiyu Zhou, MD, PhD

The Seventh Affiliated Hospital, Sun Yat-sen University, Co-PI

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AO CMF BOOST Clinical Priority Program