Daniel Boyd

FDA approved guidance conduits and wraps for peripheral nerve injury: A review of materials and efficacy

Several nerve guidance conduits (NGCs) and nerve protectant wraps are approved by the US Food and Drug Administration (FDA) for clinical use in peripheral nerve repair. These devices cover a wide range of natural and synthetic materials, which may or may not be resorbable. This review consolidates the data pertaining to all FDA approved materials into a single reference, which emphasizes material composition alongside pre-clinical and clinical safety and efficacy (where possible). This article also summarizes the key advantages and limitations for each material as noted in the literature (with respect to the indication considered). In this context, this review provides a comprehensive reference for clinicians which may facilitate optimal material/device selection for peripheral nerve repair. For materials scientists, this review highlights predicate devices and evaluation methodologies, offering an insight into current deficiencies associated with state-of-the-art materials and may help direct new technology developments and evaluation methodologies thereof.

Hydrogel/bioactive glass composites for bone regeneration applications: Synthesis and characterisation

Due to the deficiencies of current commercially available biological bone grafts, alternative bone graft substitutes have come to the forefront of tissue engineering in recent times. The main challenge for scientists in manufacturing bone graft substitutes is to obtain a scaffold that has sufficient mechanical strength and bioactive properties to promote formation of new tissue. The ability to synthesise hydrogel based composite scaffolds using photopolymerisation has been demonstrated in this study. The prepared hydrogel based composites were characterised using techniques including Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), Energy-dispersive X-ray spectrometry (EDX), rheological studies and compression testing. In addition, gel fraction, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), porosity and swelling studies of the composites were carried out. It was found that these novel hydrogel bioglass composite formulations did not display the inherent brittleness that is typically associated with bioactive glass based bone graft materials and exhibited enhanced biomechanical properties compared to the polyethylene glycol hydrogel scaffolds along. Together, the combination of enhanced mechanical properties and the deposition of apatite on the surface of these hydrogel based composites make them an ideal candidate as bone graft substitutes in cancellous bone defects or low load bearing applications.

Effect of cellulose nanowhiskers on surface morphology, mechanical properties, and cell adhesion of melt-drawn polylactic Acid fibers.

Polylactic acid (PLA) fibers were produced with an average diameter of 11.2 (± 0.9) μm via a melt-drawing process. The surface of the PLA fibers was coated with blends of cellulose nanowhiskers (CNWs) (65 to 95 wt %) and polyvinyl acetate (PVAc). The CNWs bound to the smooth PLA fiber surface imparted roughness, with the degree of roughness depending on the coating blend used. The fiber tensile modulus increased 45% to 7 GPa after coating with 75 wt % CNWs compared with the uncoated PLA fibers, and a significant increase in the fiber moisture absorption properties at different humidity levels was also determined. Cytocompatibility studies using NIH-3T3 mouse fibroblast cells cultured onto CNWs-coated PLA surface revealed improved cell adhesion compared with the PLA control, making this CNW surface treatment applicable for biomedical and tissue engineering applications. Initial studies also showed complete cell coverage within 2 days.

Enhancement of bone consolidation in mandibular distraction osteogenesis: A contemporary review of experimental studies involving adjuvant therapies

BACKGROUND One of the major disadvantages of mandibular distraction osteogenesis (MDO) is the prolonged time required for consolidation of the regenerate bone. The objective of the present study is to perform a contemporary review of various adjuvant therapies to enhance bone consolidation in MDO. METHODS A PubMed search for articles related to MDO, along with the references of those articles, was performed. Inclusion and exclusion criteria were applied to all experimental studies assessing adjuvant therapies to enhance bone consolidation. RESULTS A total of 1414 titles and abstracts were initially reviewed; 61 studies were included for full review. Many studies involved growth factors, hormones, pharmacological agents, gene therapy, and stem cells. Other adjuvant therapies included mechanical stimulation, laser therapy, and hyperbaric oxygen. Majority of the studies demonstrated positive bone healing effects and thus adjuvant therapies remain a viable strategy to enhance and hasten the consolidation period. CONCLUSION Although most studies have demonstrated promising results, many questions still remain, such as optimal amount, timing, and delivery methods required to stimulate the most favorable bone regeneration. As well, further studies comparing various adjuvant therapies and documentation of long-term adverse effects are required prior to clinical application.

Novel adaptations to zinc–silicate glass polyalkenoate cements: The unexpected influences of germanium based glasses on handling characteristics and mechanical properties

Aluminum-free glass polyalkenoate cements (GPC) have been hindered for use as injectable bone cements by their inability to balance handling characteristics with mechanical integrity. Currently, zinc-based, aluminum-free GPCs demonstrate compression strengths in excess of 60MPa, but set in c. 1-2 min. Previous efforts to extend the setting reaction have remained clinically insufficient and are typically accompanied by a significant drop in strength. This work synthesized novel glasses based on a zinc silicate composition with the inclusion of GeO2, ZrO2, and Na2O, and evaluated the setting reaction and mechanical properties of the resultant GPCs. Germanium based GPCs were found to have working times between 5 and 10 min, setting times between 14 and 36 min, and compression strengths in excess of 30 MPa for the first 30 days. The results of this investigation have shown that the inclusion of GeO2, ZrO2, and Na2O into the glass network have produced, for the first time, an aluminum-free GPC that is clinically viable as injectable bone cements with regards to handling characteristics and mechanical properties.

Mixture designs to assess composition–structure–property relationships in SiO2–CaO–ZnO–La2O3–TiO2–MgO–SrO–Na2O glasses: Potential materials for embolization

Embolization with micron-sized particulates is widely applied to treat uterine fibroids. The objective of this work was to develop mixture designs to predict materials composition–structure–property relationships for the SiO2–CaO–ZnO–La2O3–TiO2–MgO–SrO–Na2O glass system and compare its fundamental materials properties (density and cytocompatibility), against a state-of-the-art embolic agent (contour polyvinyl alcohol) to assess the potential of these materials for embolization therapies. The glass structures were evaluated using 29Si MAS NMR to identify chemical shift and line width; the particulate densities were determined using helium pycnometry and the cell viabilities were assessed via MTT assay. 29Si MAS NMR results indicated peak maxima for each glass in the range of −82.3 ppm to −89.9 ppm; associated with Q2 to Q3 units in silicate glasses. All experimental embolic compositions showed enhanced in vitro compatibility in comparison to Contour PVA with the exceptions of ORP9 and ORP11 (containing no TiO2). In this study, optimal compositions for cell viability were obtained for the following compositional ranges: 0.095–0.188 mole fraction ZnO; 0.068–0.159 mole fraction La2O3; 0.545–0.562 mole fraction SiO2 and 0.042–0.050 mole fraction TiO2. To ensure ease of producibility in obtaining good melts, a maximum loading of 0.068 mole fraction La2O3 is required. This is confirmed by the desirability approach, for which the only experimental composition (ORP5) of the materials evaluated was presented as an optimum composition; combining high cell viability with ease of production (0.188 mole fraction ZnO; 0.068 mole fraction La2O3; 0.562 mole fraction SiO2 and 0.042 mole fraction TiO2).

Structure and diffusion of ZnO–SrO–CaO–Na2O–SiO2 bioactive glasses: a combined high energy X-ray diffraction and molecular dynamics simulations study

Novel bioactive glasses that can release ions such as strontium and zinc provide bone growth enhancement and antibacterial properties that earlier-generation bioglasses did not possess. These glasses find applications in bone cementation, restoration and in tissue engineering. In this paper, we present combined experimental and simulation studies to explain the structure and diffusion of ZnO–SrO–CaO–Na2O–SiO2 bioactive glasses with the aim of understanding the short and medium range structure of these glasses, the structural correlation to their dissolution behaviors, and their bioactivity. High energy X-ray diffraction experiments have been performed to obtain structural information and to validate the structure models from simulations. Three glass compositions with ZnO/Na2O substitutions have been studied using molecular dynamics simulations to characterize the glass structure and calculate the ionic diffusion in these glasses. The results provide insight to local environments and structural role of zinc ions, the medium range structural features such as Qn distribution, and ionic diffusion characteristics of these bioactive glasses. The structure and ionic diffusion results are discussed in correlation to the dissolution behaviors and the bioactivity of these glasses.

A Novel Glass Polyalkenoate Cement for Fixation and Stabilisation of the Ribcage, Post Sternotomy Surgery: An ex-Vivo Study

This study investigates the use of gallium (Ga) based glass polyalkenoate cements (GPCs) as a possible alternative adhesive in sternal fixation, post sternotomy surgery. The glass series consists of a Control (CaO–ZnO–SiO2), and LGa-1 and LGa-2 which contain Ga at the expense of zinc (Zn) in 0.08 mol% increments. The additions of Ga resulted in increased working time (75 s to 137 s) and setting time (113 to 254 s). Fourier Transform Infrared (FTIR) analysis indicated that this was a direct result of increased unreacted poly(acrylic acid) (PAA) and the reduction of crosslink formation during cement maturation. LGa samples (0.16 wt % Ga) resulted in an altered ion release profile, particularly for 30 days analysis, with maximum Ca2+, Zn2+, Si4+ and Ga3+ ions released into the distilled water. The additions of Ga resulted in increased roughness and decreased contact angles during cement maturation. The presence of Ga has a positive effect on the compressive strength of the samples with strengths increasing over 10 MPa at 7 days analysis compared to the 1 day results. The additions of Ga had relatively no effect on the flexural strength. Tensile testing of bovine sterna proved that the LGa samples (0.16 wt % Ga) are comparable to the Control samples.

Preliminary evaluation of therapeutic ion release from Sr-doped zinc-silicate glass ceramics

Bioactive and degradable porous bioceramics play an important role in many clinical situations. Porosity is essential to the performance of a material that is proposed to be used as an implantable osseous scaffold. Scaffolds provide a three dimensional support and template to osseous integration and vascularization. Combining the porosity of a scaffold with the ability of the scaffold material to deliver therapeutic ions to the site of implantation goes some way towards developing an ideal bone graft. A series of strontium-doped zinc silicate (Ca-Sr-Na-Zn-Si) glass ceramics scaffoldswere developed, whose porosity was measured to be between 93% and 96%, which is advantageous in terms of osseous integration and vascularization. The levels of Zn2+ and Sr2+ detected as a result of degradation of the crystalline phases were found to be 1.4–600 parts per million (ppm) and 0–583 ppm, respectively. The levels detected correlate well with the levels of Sr2+ and Zn2+ions typically associated with clinical benefits, including antibacterial efficacy, osteoblastic differentiation and impaired osteoclastic resorption.

Experimental composite guidance conduits for peripheral nerve repair: An evaluation of ion release

Poly (lactide-co-glycolide) (PLGA) - Pluronic F127 - glass composites have demonstrated excellent potential, from the perspective of controlled mechanical properties and cytocompatibility, for peripheral nerve regeneration. In addition to controlling the mechanical properties and cytotoxicity for such composite devices, the glass component may mediate specific responses upon implantation via degradation in the physiological environment and release of constituent elements. However, research focused on quantifying the release levels of such therapeutic ions from these experimental medical devices has been limited. To redress the balance, this paper explores the ion release profiles for Si(4+), Ca(2+), Na(+), Zn(2+), and Ce(4+) from experimental composite nerve guidance conduits (CNGC) comprising PLGA (at 12.5, and 20 wt.%), F127 (at 0, 2.5 and 5 wt.%) and various loadings of Si-Ca-Na-Zn-Ce glass (at 20 and 40 wt.%) for incubation periods of up to 28 days. The concentration of each ion, at various time points, was determined using Inductively Coupled Plasma-Atomic Emission Spectrometry (Perkin Elmer Optima 3000). It was observed that the Si(4+), Na(+), Ca(2+), Zn(2+) release from CNGCs in this study ranged from 0.22 to 6.477 ppm, 2.307 to 3.277 ppm, 40 to 119 ppm, and 45 to 51 ppm, respectively. The Ce(4+) concentrations were under the minimum detection limits for the ICP instrument utilized. The results indicate that the ion release levels may be appropriate to mediate therapeutic effects with respect to peripheral nerve regeneration. The data generated in this paper provides requisite evidence to optimize composition for pre-clinical evaluation of the experimental composite.