Consume or conserve: micro-roughness of titanium implants towards fabrication of dual micro-nanotopography

Combining micro-roughness of the current titanium implants for initial stability/inter-locking with nano-topography for enhanced bioactivity/drug-release may be an ideal solution to address therapeutic challenges inside the bone micro-environment. We hereby present a single-step electrochemical anodization using conditioned electrolyte to enable fabrication of aligned titania nanopores with preserved micro-scale features of the underlying titanium implant. Applicability towards the fabrication of mechanically robust and clinically translatable next-generation of orthopaedic/dental implants with dual-topography including 'gold-standard' micro-roughness and superimposed 'bioactive' nanotopography

Hydrophilic titanium surface‐induced macrophage modulation promotes pro‐osteogenic signalling

Objectives: As biomaterial‐induced modulation of mediators of the immune response may be a potential therapeutic approach to enhance wound healing events, the aim of this study was to delineate the effects of titanium surface modification on macrophage phenotype and function. Material and methods: Rodent bone marrow‐derived macrophages were polarized into M1 and M2 phenotypes and cultured on micro‐rough (SLA) and hydrophilic modified SLA (modSLA) titanium discs. Macrophage phenotype and cytokine secretion were subsequently assessed by immunostaining and ELISA, respectively. Osteoblast gene expression in response to culture in the M1 and M2 macrophage conditioned media was also evaluated over 7 days by RT‐PCR. Results: M1 macrophage culture on the modSLA surface promoted an M2‐like phenotype as demonstrated by marked CD163 protein expression, Arg1 gene expression and the secretion of cytokines that significantly upregulated in osteoblasts the expression of genes associated with the TGF‐ß/BMP signalling pathway and osteogenesis. In comparison, M2 macrophage culture on SLA surface promoted an inflammatory phenotype and cytokine profile that was not conducive for osteogenic gene expression. Conclusions: Macrophages are able to alter or switch their phenotype according to the signals received from the biomaterial surface. A hydrophilic micro‐rough titanium surface topography elicits a macrophage phenotype associated with reduced inflammation and enhanced pro‐osteogenic signalling

Bridging the gap: optimized fabrication of robust titania nanostructures on complex implant geometries towards clinical translation

Electrochemically anodized titanium surfaces with titania nanostructures (TNS; nanopores, nanotubes, etc.) have been widely applied as therapeutic bone/dental implant modifications. Despite the numerous advancements in the field of electrochemical anodization (EA), in terms of translation into the current implant market, research gaps in this domain include the lack of fabrication optimization, performed on a substrate of conventional implant surface/geometry, and inadequate mechanical stability. In the current study, we investigate the role of substrate pre-treatment on achieving desired nanotopographies for the purpose of reproducing optimized nanostructures on the complex geometry of commercial implant surfaces, as well as in-depth mechanical stability testing of these nano-engineered coatings. The results confirmed that: (a) substrate polishing/smoothening may be insignificant with respect to fabrication of well-ordered and high quality TNS on micro-rough implants with preserved underlying micro roughness; (b) optimized outcomes can be successfully translated onto complex geometries characteristic of the current implant market, including dental implant abutments and screws (also applicable to a wider implant market including orthopaedics); (c) mechanical stability testing revealed improved modulus and hardness values as compared to conventional nanotubes/pores. We believe that such optimization advances the existing knowledge of titanium anodization and anodized implants towards integration into the current implant market and successful clinical translation. (C) 2018 Elsevier Inc. All rights reserved

A Clinical Risk Assessment of a 3D-Printed Patient-Specific Scaffold by Failure Modes and Effects Analysis

This study aims to carry out a risk assessment to identify and rectify potential clinical risks of a 3D-printed patient-specific scaffold for large-volume alveolar bone regeneration. A survey was used to assess clinicians’ perceptions regarding the use of scaffolds in the treatment of alveolar defects and conduct a clinical risk assessment of the developed scaffold using the Failure Modes and Effects Analysis (FMEA) framework. The response rate was 69.4% with a total of 41 responses received. Two particular failure modes were identified as a high priority through the clinical risk assessment conducted. The highest mean Risk Priority Number was obtained by “failure of healing due to patient risk factors” (45.7 ± 27.7), followed by “insufficient soft tissue area” (37.8 ± 24.1). Despite the rapid developments, finding a scaffold that is both biodegradable and tailored to the patient’s specific defect in cases of large-volume bone regeneration is still challenging for clinicians. Our results indicate a positive perception of clinicians towards this novel scaffold. The FMEA clinical risk assessment has revealed two failure modes that should be prioritized for risk mitigation (safe clinical translation). These findings are important for the safe transition to in-human trials and subsequent clinical use

Understanding and augmenting the stability of therapeutic nanotubes on anodized titanium implants

Titanium is an ideal material choice for orthopaedic and dental implants, and hence a significant amount of research has been focused towards augmenting the therapeutic efficacy of titanium surfaces. More recently the focus has shifted to nano-engineered implants fabricated via anodization to generate self-ordered nanotubular structures composed of titania (TiO2). These structures (titania nanotubes/TNTs) enable local drug delivery and tailorable cellular modulation towards achieving desirable effects like enhanced osseointegration and antibacterial action. However, the mechanical stability of such modifications is often ignored and remains under explored, and any delamination or breakage in the TNTs modification can initiate toxicity and lead to severe immuno-inflammatory reactions. This review details and critically evaluates the progress made in relation to this aspect of TNT based implants, with a focus on understanding the interface between TNTs and the implant surface, treatments aimed at augmenting mechanical stability and strategies for advanced mechanical testing within the bone micro-environment ex vivo and in vivo. This review article extends the existing knowledge in this domain of TNTs implant technology and will enable improved understanding of the underlying parameters that contribute towards mechanically robust nano-engineered implants that can withstand the forces associated with implant surgical placement and the load bearing experienced at the bone/implant interface

Tissue integration and biodegradation of soft tissue substitutes with and without compression: an experimental study in the rat

OBJECTIVES To analyze the influence of compression on tissue integration and degradation of soft tissue substitutes. MATERIAL AND METHODS Six subcutaneous pouches in twenty-eight rats were prepared and boxes made of Al$_{2}$O$_{3}$ were implanted and used as carriers for soft tissue substitutes: a collagen matrix (MG), two volume-stable collagen matrices (FG/MGA), and a polycaprolactone scaffold(E). The volume-stable materials (FG/MGA/E) were further implanted with a twofold (2) and a fourfold (4) compression, created by the stacking of additional layers of the substitute materials. The samples were retrieved at 1, 2, and 12 weeks (10 groups, 3 time points, n = 5 per time point and group, overall, 150 samples). The area fraction of infiltrated fibroblasts and inflammatory cells was evaluated histologically. Due to within-subject comparisons, mixed models were conducted for the primary outcome. The level of significance was set at 5%. RESULTS The area fraction of fibroblasts increased in all groups over time. At 12 weeks, the densely compressed materials FG4 (1.1%), MGA4 (1.7%), and MGA2 (2.5%) obtained lower values as compared to the other groups, ranging between 4.7 (E2) and 6.5% (MG). Statistically significant differences (p ≤ 0.05) were observed between groups FG4 vs MG/FG2/E/E4 as well as between MGA4 vs MG/FG2/E/E4 and E vs MGA2. CONCLUSIONS Higher levels of compression led to delayed tissue integration. The effect of different compression levels was more distinct when compared to the differences between the materials. CLINICAL RELEVANCE All biomaterials demonstrated tissue integration and a minimal concomitant inflammatory reaction. Clinically, it might be more favorable to obtain a sufficient flap release or to reduce the material size to improve the tissue integration processes

Ten Year Clinical and Aesthetic Outcomes of an Immediately Placed and Restored Implant in the Anterior Maxilla: A Case Report

The nature of immediate implant placement followed by an immediate restoration protocol makes it particularly suited to the anterior maxilla. In addition to saving treatment time and avoiding additional surgical procedures, this protocol has been reported to improve aesthetic outcomes by supporting the peri-implant tissues during the implant healing phase through the use of a provisional restoration. This case report documents the use of this protocol in a patient with a failing maxillary anterior tooth and reports on the soft and hard tissue changes over an observation period of 10 years. An implant was immediately placed after removal of a failing maxillary central incisor followed by the provision of a screw retained provisional crown on the same day. A definitive restoration was placed after a 3-month healing period. Not only did this protocol manage to maintain peri-implant bone levels over the 10-year follow-up period, excellent aesthetic outcomes and very limited soft tissue recession were observed with the use of this technique

Towards Clinical Translation: Optimized Fabrication of Controlled Nanostructures on Implant-Relevant Curved Zirconium Surfaces

Anodization enables fabrication of controlled nanotopographies on Ti implants to offer tailorable bioactivity and local therapy. However, anodization of Zr implants to fabricate ZrO2 nanostructures remains underexplored and are limited to the modification of easy-to-manage flat Zr foils, which do not represent the shape of clinically used implants. In this pioneering study, we report extensive optimization of various nanostructures on implant-relevant micro-rough Zr curved surfaces, bringing this technology closer to clinical translation. Further, we explore the use of sonication to remove the top nanoporous layer to reveal the underlying nanotubes. Nano-engineered Zr surfaces can be applied towards enhancing the bioactivity and therapeutic potential of conventional Zr-based implants

Workflow for highly porous resorbable custom 3D printed scaffolds using medical grade polymer for large volume alveolar bone regeneration

This study investigates the design, workflow and manufacture of highly porous, resorbable additively manufactured, 3-dimensional (3D) custom scaffolds for the regeneration of large volume alveolar bone defects.Computed tomography (CT) scans of 5 posterior mandibular vertical bone defects were obtained. Surface masks (3D surface contours) of the recipient site were first isolated using a contrast threshold, transformed into 3D objects, and used to guide the formation of custom implant template models. To determine model accuracy and fit, the gap and overlap between the patient geometry models and the idealized template 3D models were quantified. Models were 3D printed from medical grade polycaprolactone (PCL) into porous scaffolds. For scaffold dimensional quantification, scaffolds were scanned using a micro-computed tomography (µCT) scanner.The design and printing processes each achieved dimensional errors of less than 200 µm on average. The average gap between the template implant model and the scanned scaffold model was found to be 74 ± 14 µm. The printed scaffold was confirmed as having a porosity of 83.91 %, a mean polymer or filament thickness of 200 ± 46 µm, and a mean pore size of 590 ± 243 µm.The approach described in this study is straightforward, adaptable to a range of patient geometries, and results in the formation of reproducible, dimensionally accurate custom implants. These highly porous 3D structures manufactured from resorbable medical grade material represent a potentially transformative technology towards the clinical implementation of scaffold guided bone regeneration procedures

Novel Nano-Engineered Biomaterials for Bone Tissue Engineering

This Special Issue of Nanomaterials explores the recent advances relating to nano-engineered strategies for biomaterials and implants in bone tissue engineering [...