Nanodiamond modified copolymer scaffolds affects tumour progression of early neoplastic oral keratinocytes.
This study aimed to evaluate the tumorigenic potential of functionalising poly(LLA-co-CL) scaffolds. The copolymer scaffolds were functionalised with nanodiamonds (nDP) or with nDP and physisorbed BMP-2 (nDP-PHY) to enhance osteoinductivity. Culturing early neoplastic dysplastic keratinocytes (DOK(Luc)) on nDP modified scaffolds reduced significantly their subsequent sphere formation ability and decreased significantly the cells' proliferation in the supra-basal layers of in vitro 3D oral neoplastic mucosa (3D-OT) when compared to DOK(Luc) previously cultured on nDP-PHY scaffolds. Using an in vivo non-invasive environmentally-induced oral carcinogenesis model, nDP scaffolds were observed to reduce bioluminescence intensity of tumours formed by DOK(Luc) + carcinoma associated fibroblasts (CAF). nDP modification was also found to promote differentiation of DOK(Luc) both in vitro in 3D-OT and in vivo in xenografts formed by DOK(Luc) alone. The nDP-PHY scaffold had the highest number of invasive tumours formed by DOK(Luc) + CAF outside the scaffold area compared to the nDP and control scaffolds. In conclusion, in vitro and in vivo results presented here demonstrate that nDP modified copolymer scaffolds are able to decrease the tumorigenic potential of DOK(Luc), while confirming concerns for the therapeutic use of BMP-2 for reconstruction of bone defects in oral cancer patients due to its tumour promoting capabilities.
Department of Clinical Dentistry, Center for Clinical Dental Research, University of Bergen, Norway; Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway; Center for International Health, Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway. Electronic address: salwa.suliman@uib.no.
Salwa
S
Suliman
Department of Clinical Dentistry, Center for Clinical Dental Research, University of Bergen, Norway.
Kamal
K
Mustafa
Institute of Organic Chemistry, University of Würzburg, Würzburg, Germany.
Anke
A
Krueger
DiaCoating GmbH, Innsbruck, Austria.
Doris
D
Steinmüller-Nethl
Department of Fibre and Polymer Technology, KTH, Royal Institute of Technology, Stockholm, Sweden.
Anna
A
Finne-Wistrand
Department of Clinical Science, Hematology Section, University of Bergen, Bergen, Norway.
Tereza
T
Osdal
Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway.
Amani O
AO
Hamza
Department of Clinical Dentistry, Center for Clinical Dental Research, University of Bergen, Norway; Department of Fibre and Polymer Technology, KTH, Royal Institute of Technology, Stockholm, Sweden.
Yang
Y
Sun
Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway; Center for International Health, Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
Himalaya
H
Parajuli
Institute of Organic Chemistry, University of Würzburg, Würzburg, Germany.
Thilo
T
Waag
Chair Tissue Engineering and Regenerative Medicine, University Hospital Würzburg, Germany; Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Translational Center 'Regenerative Therapies for Oncology and Musculoskeletal Diseases'- Würzburg Branch, Germany.
Joachim
J
Nickel
Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway; Department of Pathology, Haukeland University Hospital, Bergen, Norway; Centre for Cancer Biomarkers, Department of Clinical Medicine, University of Bergen, Bergen, Norway.
Anne Christine
AC
Johannessen
Department of Clinical Science, Hematology Section, University of Bergen, Bergen, Norway; Department of Medicine, Haematology Section, Haukeland University Hospital, Bergen, Norway.
Emmet
E
McCormack
Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway; Center for International Health, Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Department of Pathology, Haukeland University Hospital, Bergen, Norway; Centre for Cancer Biomarkers, Department of Clinical Medicine, University of Bergen, Bergen, Norway. Electronic address: daniela.costea@uib.no.
Daniela Elena
DE
Costea
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009061:Mouth Mucosa / Q000473:pathology; D009062:Mouth Neoplasms / Q000628:therapy*; D058612:Nanodiamonds / Q000737:chemistry* / Q000627:therapeutic use*; D061848:Optical Imaging; D011091:Polyesters / Q000737:chemistry*; D054457:Tissue Scaffolds
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D058612:Nanodiamonds; D011091:Polyesters; C062968:lactide-caprolactone copolymer
BMP-2; Biocompatibility; Bone tissue engineering; Microenvironment; Oral squamous cell carcinoma; Tumorigenicity