Nanodiamond modified copolymer scaffolds affects tumour progression of early neoplastic oral keratinocytes
Please always quote using this URN: urn:nbn:de:bvb:20-opus-188287
- 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 toThis 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.…
Author: | Salwa Suliman, Kamal Mustafa, Anke Krueger, Doris Steinmüller-Nethl, Anna Finne-Wistrand, Tereza Osdal, Amani O. Hamza, Yang Sun, Himalaya Parajuli, Thilo Waag, Joachim Nickel, Anne Christine Johannessen, Emmet McCormack, Daniela Elena Costea |
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URN: | urn:nbn:de:bvb:20-opus-188287 |
Document Type: | Journal article |
Faculties: | Fakultät für Chemie und Pharmazie / Institut für Organische Chemie |
Medizinische Fakultät / Lehrstuhl für Tissue Engineering und Regenerative Medizin | |
Language: | English |
Parent Title (English): | Biomaterials |
Year of Completion: | 2016 |
Volume: | 95 |
Pagenumber: | 11-21 |
Source: | Biomaterials (2016) 95, 11-21. https://doi.org/10.1016/j.biomaterials.2016.04.002 |
DOI: | https://doi.org/10.1016/j.biomaterials.2016.04.002 |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 547 Organische Chemie |
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit | |
Tag: | BMP-2; Biocompatibility; Biodegradable polymer scaffolds; Bone morphogenetic protein-2; Bone tissue engineering; Growth; BMP-2; In-vitro; Mandibular continuity defects; Marrow stromal cells; Mesenchymal transition; Microenvironment; Oral squamous cell carcinoma; Sinus floor augmentation; Squamous-cell carcinoma; Tumorigenicity |
Release Date: | 2020/06/04 |
EU-Project number / Contract (GA) number: | 242175-VascuBone |
OpenAIRE: | OpenAIRE |
Licence (German): | CC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitungen 4.0 International |