Frontiers in Bioengineering and Biotechnology (Jul 2024)
Hydrogel-chitosan and polylactic acid-polycaprolactone bioengineered scaffolds for reconstruction of mandibular defects: a preclinical in vivo study with assessment of translationally relevant aspects
- Marco Ferrari,
- Marco Ferrari,
- Marco Ferrari,
- Stefano Taboni,
- Stefano Taboni,
- Stefano Taboni,
- Stefano Taboni,
- Harley H. L. Chan,
- Jason Townson,
- Tommaso Gualtieri,
- Tommaso Gualtieri,
- Leonardo Franz,
- Leonardo Franz,
- Alessandra Ruaro,
- Alessandra Ruaro,
- Alessandra Ruaro,
- Smitha Mathews,
- Michael J. Daly,
- Catriona M. Douglas,
- Catriona M. Douglas,
- Catriona M. Douglas,
- Donovan Eu,
- Donovan Eu,
- Donovan Eu,
- Axel Sahovaler,
- Axel Sahovaler,
- Axel Sahovaler,
- Nidal Muhanna,
- Nidal Muhanna,
- Manuela Ventura,
- Manuela Ventura,
- Kamol Dey,
- Kamol Dey,
- Stefano Pandini,
- Chiara Pasini,
- Federica Re,
- Federica Re,
- Simona Bernardi,
- Simona Bernardi,
- Katia Bosio,
- Katia Bosio,
- Davide Mattavelli,
- Davide Mattavelli,
- Francesco Doglietto,
- Francesco Doglietto,
- Shrinidh Joshi,
- Ralph W. Gilbert,
- Piero Nicolai,
- Piero Nicolai,
- Sowmya Viswanathan,
- Luciana Sartore,
- Domenico Russo,
- Jonathan C. Irish,
- Jonathan C. Irish
Affiliations
- Marco Ferrari
- Guided Therapeutics (GTx) Program International Scholarship, University Health Network (UHN), Toronto, ON, Canada
- Marco Ferrari
- Section of Otorhinolaryngology-Head and Neck Surgery, Department of Neurosciences, University of Padua, Padua, Italy
- Marco Ferrari
- Unit of Otorhinolaryngology-Head and Neck Surgery, Azienda Ospedale-Università di Padova, Padova, Italy
- Stefano Taboni
- Guided Therapeutics (GTx) Program International Scholarship, University Health Network (UHN), Toronto, ON, Canada
- Stefano Taboni
- Section of Otorhinolaryngology-Head and Neck Surgery, Department of Neurosciences, University of Padua, Padua, Italy
- Stefano Taboni
- Unit of Otorhinolaryngology-Head and Neck Surgery, Azienda Ospedale-Università di Padova, Padova, Italy
- Stefano Taboni
- Artificial Intelligence in Medicine and Innovation in Clinical Research and Methodology (PhD Program), Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
- Harley H. L. Chan
- Guided Therapeutics (GTx) Program, Techna Institute, University Health Network, Toronto, ON, Canada
- Jason Townson
- Guided Therapeutics (GTx) Program, Techna Institute, University Health Network, Toronto, ON, Canada
- Tommaso Gualtieri
- Guided Therapeutics (GTx) Program International Scholarship, University Health Network (UHN), Toronto, ON, Canada
- Tommaso Gualtieri
- Department of Otorhinolaryngology, Head & Neck Surgery, Nuovo Santo Stefano Civil Hospital, Prato, Italy
- Leonardo Franz
- Guided Therapeutics (GTx) Program International Scholarship, University Health Network (UHN), Toronto, ON, Canada
- Leonardo Franz
- Section of Otorhinolaryngology-Head and Neck Surgery, Department of Neurosciences, University of Padua, Padua, Italy
- Alessandra Ruaro
- Guided Therapeutics (GTx) Program International Scholarship, University Health Network (UHN), Toronto, ON, Canada
- Alessandra Ruaro
- Section of Otorhinolaryngology-Head and Neck Surgery, Department of Neurosciences, University of Padua, Padua, Italy
- Alessandra Ruaro
- Unit of Otorhinolaryngology-Head and Neck Surgery, Azienda Ospedale-Università di Padova, Padova, Italy
- Smitha Mathews
- Osteoarthritis Program, Schroeder Arthritis Institute, Krembil Research Institute, Institute of Biomedical Engineering, University Health Network, University of Toronto, Toronto, ON, Canada
- Michael J. Daly
- Guided Therapeutics (GTx) Program, Techna Institute, University Health Network, Toronto, ON, Canada
- Catriona M. Douglas
- Guided Therapeutics (GTx) Program, Techna Institute, University Health Network, Toronto, ON, Canada
- Catriona M. Douglas
- Princess Margaret Cancer Centre, Toronto General Hospital, Department of Otolaryngology-Head and Neck Surgery/Surgical Oncology, University Health Network, Toronto, ON, Canada
- Catriona M. Douglas
- Department of Otolaryngology, Head and Neck Surgery, Queen Elizabeth University Hospital, Glasgow, United Kingdom
- Donovan Eu
- Guided Therapeutics (GTx) Program, Techna Institute, University Health Network, Toronto, ON, Canada
- Donovan Eu
- Princess Margaret Cancer Centre, Toronto General Hospital, Department of Otolaryngology-Head and Neck Surgery/Surgical Oncology, University Health Network, Toronto, ON, Canada
- Donovan Eu
- 0Department of Otolaryngology-Head and Neck Surgery, National University Hospital, Singapore, Singapore
- Axel Sahovaler
- Guided Therapeutics (GTx) Program, Techna Institute, University Health Network, Toronto, ON, Canada
- Axel Sahovaler
- Princess Margaret Cancer Centre, Toronto General Hospital, Department of Otolaryngology-Head and Neck Surgery/Surgical Oncology, University Health Network, Toronto, ON, Canada
- Axel Sahovaler
- 1Head & Neck Surgery Unit, University College London Hospitals, London, United Kingdom
- Nidal Muhanna
- Guided Therapeutics (GTx) Program, Techna Institute, University Health Network, Toronto, ON, Canada
- Nidal Muhanna
- 2Department of Otolaryngology-Head and Neck Surgery, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel
- Manuela Ventura
- 3STTARR Innovation Centre, University Health Network, Toronto, ON, Canada
- Manuela Ventura
- 4Human Technopole Foundation, Milan, Italy
- Kamol Dey
- 5Department of Mechanical and Industrial Engineering, University of Brescia Via Branze, Brescia, Italy
- Kamol Dey
- 6Department of Applied Chemistry and Chemical Engineering, Faculty of Science, University of Chittagong, Chittagong, Bangladesh
- Stefano Pandini
- 5Department of Mechanical and Industrial Engineering, University of Brescia Via Branze, Brescia, Italy
- Chiara Pasini
- 5Department of Mechanical and Industrial Engineering, University of Brescia Via Branze, Brescia, Italy
- Federica Re
- 7Unit of Blood Diseases and Bone Marrow Transplantation, Department of Clinical and Experimental Sciences, ASST Spedali Civili, University of Brescia, Brescia, Italy
- Federica Re
- 8Centro di Ricerca Emato-Oncologica AIL (CREA), ASST Spedali Civili, Brescia, Italy
- Simona Bernardi
- 7Unit of Blood Diseases and Bone Marrow Transplantation, Department of Clinical and Experimental Sciences, ASST Spedali Civili, University of Brescia, Brescia, Italy
- Simona Bernardi
- 8Centro di Ricerca Emato-Oncologica AIL (CREA), ASST Spedali Civili, Brescia, Italy
- Katia Bosio
- 7Unit of Blood Diseases and Bone Marrow Transplantation, Department of Clinical and Experimental Sciences, ASST Spedali Civili, University of Brescia, Brescia, Italy
- Katia Bosio
- 8Centro di Ricerca Emato-Oncologica AIL (CREA), ASST Spedali Civili, Brescia, Italy
- Davide Mattavelli
- 9Unit of Otorhinolaryngology-Head and Neck Surgery, ASST Spedali Civili of Brescia, Brescia, Italy
- Davide Mattavelli
- 0Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy
- Francesco Doglietto
- 1Neurosurgery Unit, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy
- Francesco Doglietto
- 2Catholic University School of Medicine, Rome, Italy
- Shrinidh Joshi
- Osteoarthritis Program, Schroeder Arthritis Institute, Krembil Research Institute, Institute of Biomedical Engineering, University Health Network, University of Toronto, Toronto, ON, Canada
- Ralph W. Gilbert
- Princess Margaret Cancer Centre, Toronto General Hospital, Department of Otolaryngology-Head and Neck Surgery/Surgical Oncology, University Health Network, Toronto, ON, Canada
- Piero Nicolai
- Section of Otorhinolaryngology-Head and Neck Surgery, Department of Neurosciences, University of Padua, Padua, Italy
- Piero Nicolai
- Unit of Otorhinolaryngology-Head and Neck Surgery, Azienda Ospedale-Università di Padova, Padova, Italy
- Sowmya Viswanathan
- Osteoarthritis Program, Schroeder Arthritis Institute, Krembil Research Institute, Institute of Biomedical Engineering, University Health Network, University of Toronto, Toronto, ON, Canada
- Luciana Sartore
- 5Department of Mechanical and Industrial Engineering, University of Brescia Via Branze, Brescia, Italy
- Domenico Russo
- 7Unit of Blood Diseases and Bone Marrow Transplantation, Department of Clinical and Experimental Sciences, ASST Spedali Civili, University of Brescia, Brescia, Italy
- Jonathan C. Irish
- Guided Therapeutics (GTx) Program, Techna Institute, University Health Network, Toronto, ON, Canada
- Jonathan C. Irish
- Princess Margaret Cancer Centre, Toronto General Hospital, Department of Otolaryngology-Head and Neck Surgery/Surgical Oncology, University Health Network, Toronto, ON, Canada
- DOI
- https://doi.org/10.3389/fbioe.2024.1353523
- Journal volume & issue
-
Vol. 12
Abstract
Background: Reconstruction of mandibular bone defects is a surgical challenge, and microvascular reconstruction is the current gold standard. The field of tissue bioengineering has been providing an increasing number of alternative strategies for bone reconstruction.Methods: In this preclinical study, the performance of two bioengineered scaffolds, a hydrogel made of polyethylene glycol-chitosan (HyCh) and a hybrid core-shell combination of poly (L-lactic acid)/poly (ε-caprolactone) and HyCh (PLA-PCL-HyCh), seeded with different concentrations of human mesenchymal stromal cells (hMSCs), has been explored in non-critical size mandibular defects in a rabbit model. The bone regenerative properties of the bioengineered scaffolds were analyzed by in vivo radiological examinations and ex vivo radiological, histomorphological, and immunohistochemical analyses.Results: The relative density increase (RDI) was significantly more pronounced in defects where a scaffold was placed, particularly if seeded with hMSCs. The immunohistochemical profile showed significantly higher expression of both VEGF-A and osteopontin in defects reconstructed with scaffolds. Native microarchitectural characteristics were not demonstrated in any experimental group.Conclusion: Herein, we demonstrate that bone regeneration can be boosted by scaffold- and seeded scaffold-reconstruction, achieving, respectively, 50% and 70% restoration of presurgical bone density in 120 days, compared to 40% restoration seen in spontaneous regeneration. Although optimization of the regenerative performance is needed, these results will help to establish a baseline reference for future experiments.
Keywords
- bone regeneration
- porous scaffold
- osteogenesis
- mesenchymal stromal cells
- tissue engineering
- head and neck
