Craniofacial therapy: advanced local therapies from nano-engineered titanium implants to treat craniofacial conditions

Abstract

Nano-engineering-based tissue regeneration and local therapeutic delivery strategies show significant potential to reduce the health and economic burden associated with craniofacial defects, including traumas and tumours. Critical to the success of such nano-engineered non-resorbable craniofacial implants include load-bearing functioning and survival in complex local trauma conditions. Further, race to invade between multiple cells and pathogens is an important criterion that dictates the fate of the implant. In this pioneering review, we compare the therapeutic efficacy of nano-engineered titanium-based craniofacial implants towards maximised local therapy addressing bone formation/resorption, soft-tissue integration, bacterial infection and cancers/tumours. We present the various strategies to engineer titanium-based craniofacial implants in the macro-, micro- and nano-scales, using topographical, chemical, electrochemical, biological and therapeutic modifications. A particular focus is electrochemically anodised titanium implants with controlled nanotopographies that enable tailored and enhanced bioactivity and local therapeutic release. Next, we review the clinical translation challenges associated with such implants. This review will inform the readers of the latest developments and challenges related to therapeutic nano-engineered craniofacial implants.

Fig. 1

Craniofacial therapy. Craniofacial defects and ailments require extensive local therapeutic administration

Fig. 2

Classification of therapeutic molecules towards craniomaxillofacial bone regeneration. Adapted with permission from ref.

Fig. 3

Growth factor releasing implants towards osseointegration. The histological sections of peri-implant bone around HA and VEGF-HA modified Ti implants. Optical micrographs of histological sections showed significantly thicker trabecular around VEGF-HA loaded Ti implants (b) than HA-coated counterparts (a) at 12 weeks within sheep tibiae. The yellow arrows indicate the newly formed blood vessels abundant around VEGF-HA loaded Ti implants. Reproduced with permission from ref.

Fig. 4

Nanotubular implants towards craniosynostosis therapy. Schematic representation of titania nanotubes (TNTs) modified Ti implants towards craniosynostosis therapy. Local controlled release of glypicans (GPC) and its influence on bone morphogenetic protein 2 (BMP2) signalling pathway via dual luciferase reporter (DLR) assay. Adapted with permission from ref.

Fig. 5

Drug eluting implants address dental implants’ soft-tissue integration (STI) challenges. Scheme showing a dental implant and transmucosal region; b peri-implantitis; c surface modification to achieve STI; and d next generation of modified therapeutic implants releasing active drugs/proteins directly inside the transmucosal region. Adapted with permission from ref.

Fig. 6

Antibacterial surface modification of Ti implants. Schematic representation: a various physical/chemical surface modifications; and b electrochemically anodised Ti implants with TiO₂ nanotubes towards local elution of antibiotics. Adapted with permission from ref.

Fig. 7

Bacterial adhesion on antibiotic-releasing nanopillar surface. SEM images showing adhesion of S. aureus on a, d smooth electropolished Ti; b, e 2D TiO₂ nanopores; and c, f 3D TiO₂ nanopillars surfaces, without (top-row) and with (bottom-row) gentamicin-tannic acid coating. b Shows bacterial attachment on 3D nanopillar top and gaps between pillar bundles. f The red marking indicates an extracellular polymeric substance excreted by bacteria. g Schematic representation of bacterial adhesion on tannic acid/gentamicin coated 3D nanopillars. Scale bar a–f represents 1 µm. Adapted with permission from ref.

Fig. 8

Clinical translation challenges associated with therapeutic anodised implants. Adapted with permission from ref.