TY  - JOUR
A1  - Suliman, Salwa
A1  - Mustafa, Kamal
A1  - Krueger, Anke
A1  - Steinmüller-Nethl, Doris
A1  - Finne-Wistrand, Anna
A1  - Osdal, Tereza
A1  - Hamza, Amani O.
A1  - Sun, Yang
A1  - Parajuli, Himalaya
A1  - Waag, Thilo
A1  - Nickel, Joachim
A1  - Johannessen, Anne Christine
A1  - McCormack, Emmet
A1  - Costea, Daniela Elena
T1  - Nanodiamond modified copolymer scaffolds affects tumour progression of early neoplastic oral keratinocytes
JF  - Biomaterials
N2  - 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 DOKLuc 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.
KW  - Bone morphogenetic protein-2
KW  - Sinus floor augmentation
KW  - Marrow stromal cells
KW  - Growth; BMP-2
KW  - Tumorigenicity
KW  - Biodegradable polymer scaffolds
KW  - Mandibular continuity defects
KW  - Squamous-cell carcinoma
KW  - In-vitro
KW  - Mesenchymal transition
KW  - BMP-2
KW  - Bone tissue engineering
KW  - Biocompatibility
KW  - Microenvironment
KW  - Oral squamous cell carcinoma
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188287
VL  - 95
ER  -