StemBoneReg: Reconstruction of mandibular bone using stem cells and biomedical engineering approaches

Recent project activity

Increased emphasis is being placed on translational research discoveries, which will bring the use of stem cells in laboratory studies into the clinical setting. However, only few early stage clinical studies with a limited number of patients have proven safety of this novel regenerative treatment. According to the clinical database (www.clinicaltrials.gov) and Medline, it appears that our research is at the forefront of regenerative medicine as we have successfully performed an early stage pilot clinical study using stem cell therapy in 11 patients for reconstruction of alveolar bone with excellent results at the 24 month examination. These results pave the way for improved and well-designed phase II clinical trial using stem cell therapy for bone regeneration.

The StemRegBone project consists of a number of sub-projects including therapeutic and safety assessment in clinical trial and optimization of MSC expansion in preclinical studies.

Reconstruction of jaw/alveolar bones using stem cells and biomaterials.

Atrophied bone has a limited spontaneous healing capacity. A clinical trial is designed to demonstrate the safety and efficacy of mesenchymal stem cells (MSC) for making new bone.

Project detail

Monitoring grafted MSC using a minimally invasive diagnostic concept

The interactions between the transplanted MSCs and host immune cells is under elucidation by liquid biopsy to assess safety and immune efficacy of autologous bone marrow MSC therapy

Project detail

Optimization and production of clinical grade MSC

For the production of clinical grade, xeno-free culture condition is to be adopted. In this project, the efficacy of using Human Platelet Lysates (HPLs) as an alternative to animal serum (i.e., fatal bovine serum) is tested for MSC expansion for the application of cell transplantation therapy.

Project detail

Optimization of capacity and cost of ex-vivo expansion using bioreactors to facilitate commercialization of MSC as ATMP

In bone tissue engineering, various bioreactor systems are used to control MSC fate mechanically. In the project, mechanical regulation of MSC dynamics is assessed by applying dynamic culture conditions.

Project detail

Publication/Thesis

Shanbhag, S., Al-Sharabi, N., Kampleitner, C., Mohamed-Ahmed, S., Kristoffersen, E. K., Tangl, S., … & Sanz, M. (2023). The use of mesenchymal stromal cell secretome to enhance guided bone regeneration in comparison with leukocyte and platelet-rich fibrin.

Ahmad Rashad et al. Responses of Rat Mesenchymal Stromal Cells to Nanocellulose with Different Functional Groups. ACS Apple Bio Mater (2023)

Shanbhag Siddharth et al. Functionalizing Collagen Membranes with MSC-Conditioned Media Promotes Guided Bone Regeneration in Rat Calvarial Defects. Cells (2023)

Shuntaro Yamada et al. Unique Osteogenic Profile of Bone Marrow Stem Cells Stimulated in Perfusion Bioreactor is Rho-ROCK-mediated Contractility-Dependent. Bioeng Transl Med (2023)

Niyaz Al-Sharabi et al. Proteomic Analysis of Mesenchymal Stromal Cells Secretome in Comparison to Leukocyte- and Platelet-Rich Fibrin. Int J Mol Sci (2023)

Shuntaro Yamada et al. Translation of Biophysical Environment in Bone into Dynamic Cell Culture under Flow for Bone Tissue Engineering. Comput Struct Biotechnol J (2023)

Hassan R. W. Ali et al. Xeno-free generation of human induced pluripotent stem cells from donor-matched fibroblasts isolated from dermal and oral tissues. Stem Cell Res Ther (2023)

Neha Rana Ph.D Thesis Immunomodulatory effects of mesenchymal stromal cells and calcium phosphate scaffolds in bone regeneration. Preclinical and Clinical Studies.

Shuntaro Yamada Ph.D Thesis 3D dynamic culture of mesenchymal stem cells under fluid flow: Implications for bone regeneration.

Siddharth Shanbhag et al. Ectopic Bone Tissue Engineering in Mice Using Human Gingiva or Bone Marrow-Derived Stromal/Progenitor Cells in Scaffold-Hydrogel Constructs. Front Bioeng Biothechnol (2022)

Neha Rana et al. Systemic and local innate immune responses to surgical co-transplantation of mesenchymal stromal cells and biphasic calcium phosphate for bone regeneration. Acta Biomaterialia (2022)

Shuntaro Yamada et al. Scaffolds in Periodontal Regenerative Treatment. Dental Clinics (2022)

Neha Rana et al. Extracellular Vesicles Derived from Primed Mesenchymal Stromal Cells Loaded on Biphasic Calcium Phosphate Biomaterial Exhibit Enhanced Macrophage Polarization. Cells (2022)

Shuntaro Yamada et al. Optimisation and validation of a custom-designed perfusion bioreactor for bone tissue engineering: Flow assessment and optimal culture environmental conditions. Front Bioeng Biotechnol (2022)

Mohamad Nageeb Hassan et al. Contact Osteogenesis by Biodegradable 3D-printed Poly(lactide-co-trimethylene carbonate). Biomaterials Research (2022)

Siddharth Shanbhag et al. Effects of conditioned media from human platelet lysate cultured MSC on osteogenic cell differentiation in vitro. Front Bioeng Biothechnol (2022)

Mohamad Nageeb Hassan Ph.D Thesis 3D-printed Synthetic Polymer Templates for Bone Tissue Engineering

Yamada S et al.Induction of osteogenic differentiation of bone marrow stromal cells on 3D polyester-based scaffolds solely by subphysiological fluidic stimulation in a laminar flow bioreactor. Journal of Tissue Engineering(2021)

Yamada S et al.Surface activation with oxygen plasma promotes osteogenesis with enhanced extracellular matrix formation in three-dimensional microporous scaffolds. Journal of Biomedical Materials Research Part A(2021)

Shanbhag S et al.Spheroid coculture of human gingiva-derived progenitor cells with endothelial cells in modified platelet lysate hydrogels. Front Bioeng Biotechnol(2021)

Shanbhag S et al.Bone regeneration in rat calvarial defects using suspension or spheroid mesenchymal stromal cells. Stem Cell ResTher (2021)

Helgeland E et al.3D printed gelatin scaffolds for temporomandibular joint cartilage regeneration. Biomed Phys Eng Express (2021)

Helgeland E et al.Dual-crosslinked 3D printed gelatin scaffolds with potential for temporomandibular joint cartilage regeneration. Biomed Mater (2021)

Mohamed-Ahmed I et al.Comparison of bone regenerative capacity of donor-matched human adipose-derived and bone marrow mesenchymal stem cells.Cell Tissue Res(2021)

Ragda Saleem et al. Bone Marrow Mesenchymal Stem Cells Restored Oxidative Stress-Related Impaired Osteogenic Differentiation. Int J Mol Sci (2021)

Gjerde C et al.Patient experience following iliac crest-derived alveolar bone grafting and implant placement.International J Implant Dentistry.(2020)
Shanbhag S et al.Xeno-free spheroids of human gingiva-derived progenitor cells for bone tissue engineering.Front Bioeng Biotechnol.(2020)
Shanbhag S et al.Influence of platelets storage time on human platelet lysates and platelet lysate-expanded mesenchymal stromal cells for bone tissue engineering.Stem Cell Res Ther.(2020)
Helgeland E et al.Angiostatin-functionalized collagen scaffolds suppress angiogenesis but do not induce chondrogenesis by mesenchymal stromal cells in vivo.J Oral Sci.(2020)
Jain S et al.Engineering 3D degradable,pliable scaffolds toward adipose tissue regeneration;optimized printability,simulations and surface modification.J Tissue Eng.(2020)

Shanbhag S et al.Cell therapy for orofacial bone regeneration:a systematic review and meta-analysis.J Clin Periodontol.(2019)
Hassan MN et al.The Bone Regeneration Capacity of 3D-Printed Templates in Calvarial Defect Models:A Systematic Review and Meta-Analysis.Acta Biomaterialia.(2019)
Ojansivu M et al.Wood-based nanocellulose and bioactive glass modified gelatin-alginate bioinks for 3D bioprinting of bone cells.Biofabrication.(2019)
Rashad A et al.Inflammatory Responses and Host Tissue Reactions to Wood-Based Nanocellulose Scaffolds.Materials Science&Engineering C Mater Biol Appl.(2019)

Dissemination in international conferences

October 2023 2nd Annual TOR symposium

Center of Translational Oral Research (TOR), UiB
Bergen, Norway

Contribution

Kamal Mustafa – Organizer
Åshild Johansen – Oral Presentation
Triazine-trione based composite materials for potential bone tissue engineering

September 2023 31st Annual Meeting of the European Orthopaedic Research Society (EORS)

European Orthopaedic Research Society
Porto, Portogul

Contribution

Cecilie Gjorde -Keynote speaker
Stem cells in bone regeneration, the future is NOW
Niyaz Al-Sharabi- Oral presentation
Extracellular Vesicles Secreted by Osteogenic-Differentiated Mesenchymal Stem Cells Promote Bone Formation in Rat Calvarial Defect
Samih Mohamed-Ahmed – Oral Presentation
Source of mesenchymal stem cells is vital for bone regenerative applications
Åshild Johansen – Oral Presentation
Triazine-trione based composite materials for potential bone tissue engineering
Mehmet Serhat Aydin – Oral Presentation
Phase separation and particulate leaching integrated 3D printing of porous scaffolds for bone tissue engineering applications

September 2023 ESB 2023

European Society for Biomaterials
Davos, Swizerland

Contribution

Masoumeh Jahani Kadousaraei – Poster presentation
Theo Luciani – Poster Presentation
Francesco Torelli – Oral Presentation

June 2023 2023 IADR/LAR General Session & Exhibition with WCPD

International Association of Dental, Oral, and Craniofacial Research
Bogota, Colombia

Contribution

Shuntaro Yamada – Invited SpeakerOsteogenic profile of mechanically stimulated mesenchymal stem cells

June 2022 TERMIS EU-Chapter

Tissue Engineering and Regenerative Medicine International Society
Kraków, Polan
Contribution

Kamal Mustafa -Symposium Chair
New insights underlying mesenchymal stem cell-mediated bone regeneration
Cecilie Gjerde – Invited Speaker
Stem Cells in Bone Regeneration A randomized Clinical Trial
Shuntaro Yamada – Oral Presentation
Fluid-flow mediated cytoskeletal adaptation regulates the growth and fate of bone marrow mesenchymal stem cells
Jannika Korkeamäki – Oral Presentation
Development of angiogenic bioink for vascularized bone tissue engineering

June 2022 Translational Oral Research Workshop
Center of Translational Oral Research, UiB
Bergen, Norway
Contribution

Cecilie Gjerde – Oral Presentation
Cell therapy in clinical studies
Siddharth Shanbhag – Oral Presentation
Clinical-grade cell and cell-free therapies for bone regeneration
Shuntaro Yamada – Oral Presentation
Dynamic Cell Culture Platform: Strategic Application for Tissue Engineering
Jannina Korkeamäki – Oral Presentation
3D-Printing and Biofabrication: A Step Forward

June 2022 Europerio 10

European Federation of Periodontology
Copenhagen, Denmark
Contribution

Cecilie Gjerde – Invited Speaker
The use of Mesenchymal Stem Cells and synthetic biomaterials in oral bone regeneration
Siddharth Shanbhag – Oral Presentation
Cell-secretome functionalized collagen membranes promote in vivo guided bone regeneration

August 2022 TOR Opening Seminar

Center of Translational Oral Research, UiB
Bergen, Norway
Contribution

Shuntaro Yamada – Oral Presentation
Mechanical regulation of stem cell fate for tissue engineering using a novel bioreactor

September 2022 PER-IADR Oral Health Research Congress

Pan European Division of International Association for Dental Research
Marseille, France
Contribution

Kamal Mustafa – Symposium Chair
Symposium Stem Cells in Bone Regeneration – Future is Now
Shuntaro Yamada – Oral Presentation
Osteogenic Profile of Mechanically Stimulated Mesenchymal Stem Cells
NOF Hatton Award

October 2022 Norsk Tannlegeforening Landsmøte
Oslo, Norway
Contribution

Siddharth Shanbhag – Oral Presentation
Nye strategier for beinregenerasjon: Vekstfaktorer fra stamceller

Shuntaro Yamada, Poster presentation, Long-term low-magnitude fluid shear stress directs bone marrow mesenchymal stem cells toward osteogenic lineage
TERMIS 6th World Congress, Netherland

2020,Invited speaker,Kamal Mustafa,2020 Award for Best Research Group at Faculty of Medicine,UiB
2020,Invited speakers,Kamal Mustafa and Cecilie Gjerde,Olav Thon Nordic Award
2020,Invited speaker,Cecilie Gjerde,Quo Vadis Periodontics Symposium(1 000 participants).
2020,Invited speaker,Kamal Mustafa,University of Khartoum,Sudan
2020,Invited speaker,Cecilie Gjerde,Forsker Grand Prix meeting,Bergen
2020,Invited speaker,Kamal Mustafa,IKO and IGS meeting at UiB

2019,Invited speaker,University of Helsinki,Finland
2019,Speaker,Cecilie Gjerde,International Faculty Form in Mainz,Germany
2019,Speaker,Cecilie Gjerde,ITI Section meeting in Bergen.
2019,Speaker,Cecilie Gjerde,IADR,Vancouver,Canada.
2019,Speaker,Cecilie Gjerde,Research meeting,University of Tromsø.
2019,Keynote Speaker for Plenary Session and Opening Ceremony,Kamal Mustafa,Plenary session,European Association for Osseointegration(EAO)Meeting,Lisbon,Portugal.Title:Are stem cells the implants of the future.
2019,Invited Speaker,Kamal Mustafa,NYSCO Annual Meeting,Oslo,Norway.Title:From bench to chairside:Stem cells in bone augmentation.
2019,Invited Speaker,Kamal Mustafa,BioVaria Meeting,Munich,Germany.Bone from the 3D printer.
2019,Invited Speaker,Kamal Mustafa,AMCHA 2019 Meeting,Sri Lanka.Title:Stem cells in bone regeneration,a systematic approach and pilot study in humans.
2018,Invited Speaker,Kamal Mustafa,Joint Workshop in Stem Cells and Regenerative Medicine,Tokyo,Japan.Title:MSC and Biomaterial for Bone Regeneration.
2019,Cecilie Gjerde et al.Stem cells in bone regeneration,a clinical trial with 3 years follow-up,Tissue Engineering and Regenerative Medicine(TERMIS),Brisbane,Australia,oral presentation,2019.
2019,Jannika Paulamäki.Development of Nanostructured Alginate-Gelatin-Based Inks for 3D Bioprinting of Bone Cells.Biofabrication Conference,Columbus OH,USA,Oral Presentation.
2019,Cecilie Gjerde,invited speaker.Bergen Stem Cell Consortium meeting,Bergen Norway.Title:stamcelleforskningen.
2019,Shuntaro Yamada.Plasma activation of polymeric biomaterial enhanced initial adhesion and seeding efficiency of mesenchymal stromal cells.Bergen Stem Cell Consortium meeting,Bergen Norway.Oral Presentation(prize for best presentation).
2019,Cecilie Gjerde,Invited Speaker;Orthopedic department,Int conf Merch,Norway,Cell therapy induced regeneration in severely atrophied mandibular bone.
2019,Cecilie Gjerde,Bergen Dental Health Center,Autumn meeting,Bergen,Norway.Invited Speaker,Beinoppbygging med egne stamceller Bergensmodellen.
2019,Cecilie Gjerde,oral presentation,stem cells for bone regeneration,the future is now!IADR,Vancouver,Canada.
2019,June.Stem cell research for x-ray,HUS,Norway.Invited Speaker:Cecilie Gjerde.Title:Beinoppbygging med egne stamceller Bergensmodellen
2019,Jannika Paulamäki,Characterization of the Printability of Alginate-Gelatin Bioink Blended with Nanocellulose,Scandinavian Society for Biomaterials,Conference,Helsinki,Oral presentation,Award.

The Trond Mohn Foundation was founded in 2004 by means of a donation from Trond Mohn. The gifts of the Mohn family are unique. They give the research communities an outstanding advantage in the long-term work of establishing research and building expertise at a high international level, both in Bergen and in the rest of Norway.
https://mohnfoundation.no/?lang=en