Nanodiamond modified copolymer scaffolds affects tumour progression of early neoplastic oral keratinocytes

Abstract

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.

In Situ Silication of Polymer Nanofibers to Engineer Multi‐Biofunctional Composites

“…Bioactive silica ceramic fillers are potential substitutes for biomolecules such as growth factors to impart bioactivity to the polymers ,. Growth factors are expensive, limit the processability of polymers for the preparation of scaffolds as they are labile and enhance the risk of cancer . A few studies on evaluating polymer composites based on silica containing bioceramics for bone tissue engineering have been reported .…”

Nanodiamonds for In Vivo Applications

“…Examples of different drug delivery strategies that have been tested in vivo. The strategies include the delivery of genetic material (1), (2), embedding the particles into a polymer film or scaffold (3), (4) as well as attachment of a number of different cancer drugs or combinations of cancer drugs and molecules that promote accumulation in cancer cells (5), (6), (7), (8), (9) …”

“…Another approach for drug delivery is to use a scaffold that delivers the drugs. Incorporation of drug‐loaded nanodiamonds into such a scaffold was recently employed by Suliman et al in mice . They used a copolymer containing poly l ‐lactide and ε‐caprolactone as monomer units in which they incorporated the detonation nanodiamonds which were coated with a bone morphogenetic protein (BMP2).…”

“…In order to promote bone formation, Zhang et al incorporated nanodiamonds that were coated with phospholipids inside a poly(lactic‐ co ‐glycolic acid) matrix . The difference to the previous article (Suliman et al) is that here, the phospholipids are not a drug compound but merely help to suspend nanodiamonds in the polymer material . The material was implanted in mice where the polymer was degraded (slower in presence of diamond) and is replaced by new bone material.…”

Multifunctional nanodiamonds in regenerative medicine: Recent advances and future directions

“…Furthermore, the ND coatings displayed localized anti-inflammatory effects due to their function in inhibiting the adhesion of inflammatory cells [129]. A subsequent study from the same group studied the osteogenic functions and tumorigenic potential of the PLCL scaffolds coated with NDs and the same scaffolds coated with ND-BMP complexes [162]. The presence of the hydroxylated NDs on the surface of the scaffolds was reported to cause a significant reduction in tumor growth when administered in vitro to dysplastic oral keratinocytes.…”