In vivo analysis of a proprietary glass-based adhesive for sternal fixation and stabilization using rabbit and sheep models.

Wire cerclage remains the standard method of care for sternal fixation, following median sternotomy, despite being beset with complications. An emerging treatment option has been to augment the wires with an adhesive. A patented ionomeric glass (mole fraction: SiO2:0.48, ZnO:0.36, CaO:0.12, SrO:0.04) has been used to formulate GPC+, a glass polyalkenoate cement (GPC), by mixing it with poly(acrylic) acid (PAA) and de-ionized water. In a human cadaver study, this material, when applied with wire cerclage, was able to significantly reduce sternal instability. However, the material has yet to be tested in pertinent animal models. Here, after a series of physical and mechanical tests to confirm suitability of the experimental material for implantation, three samples of GPC+ were implanted in either the tibia or femur of three different rabbits, alongside sham defects, for two different time modalities. A further seven samples of GPC+ and one poly(methyl methacrylate) control (PMMA) were implanted in either the tibia or femur of two different sheep. The sheep containing the PMMA was sacrificed at 8 weeks and the other at 16 weeks, to evaluate time dependent biological response. Upon sacrifice, microCT images were acquired and histology slides prepared for analysis. All three GPC+ samples implanted in the rabbit model, for the two time modalities, were characterized by minimal bone resorption along with a mild inflammatory response. Five of the seven GPC+ materials implanted in the sheep model (all three implanted for 8 weeks and two of those implanted for 16 weeks) were associated with mild to moderate immune response, comparable to that observed with PMMA, as well as mild bone resorption. The remaining two GPC + materials (implanted in the sheep model for 16 weeks) exhibited no bone resorption or inflammatory response and appeared to stimulate increased bone density at the implant site. These results suggest that GPC + can be a viable bone adhesive for use in hard tissue applications such as sternal fixation and stabilization. Experiments performed to synthesize & test Sr-doped glass adhesive for sternal fixation. (1) Sr-doped ionomeric glass fired, ground down and mixed with aqueous polyacrylic acid to produce the adhesive. (2) Adhesive characterized and tested by a suite of laboratory-based tests to ensure suitability for implantation. (3) Adhesive implanted into a rabbit model (distal femur, 12 weeks post implantation) where micro-CT images confirmed an excellent bone/cement interface, no evidence of bone resorption and some bone remodelling. (4) Adhesive subsequently implanted into a sheep model; at 16-weeks, a continuous bone-adhesive interface is seen suggesting no bone resorption. There was an increase in the peri-implant radiodensity, suggesting enhanced mineral content of the bone surrounding the GPC+ implant.

Calcium sulfate-containing glass polyalkenoate cement for revision total knee arthroplasty fixation.

Poly(methyl methacrylate) (PMMA) bone cement is used as a minor void filler in revision total knee arthroplasty (rTKA). The application of PMMA is indicated only for peripheral bone defects with less than 5 mm depth and that cover less than 50% of the bone surface. Treating bone defects with PMMA results in complications as a result of volumetric shrinkage, bone necrosis, and aseptic loosening. These concerns have driven the development of alternative bone cements. We report here on novel modified glass polyalkenoate cements (mGPCs) containing 1, 5 and 15 wt% calcium sulfate (CaSO4 ) and how the modified cements' properties compare to those of PMMA used in rTKA. CaSO4 is incorporated into the mGPC to improve both osteoconductivity and bioresorbability. The results confirm that the incorporation of CaSO4 into mGPCs decreases the setting time and increases release of therapeutic ions such as Ca2+ and Zn2+ over 30 days of maturation in deionized (DI) water. Moreover, the compressive strength for 5 and 15 wt% CaSO4 addition increased to over 30 MPa after 30 day maturation. Although the overall initial compressive strength of the mGPC (~ 30 MPa) is less than PMMA (~ 95 MPa), the compressive strength of mGPC is closer to that of cancellous bone (~ 1.2-7.8 MPa). CaSO4 addition did not affect biaxial flexural strength. Fourier transform infrared analysis indicated no cross-linking between CaSO4 and the GPC after 30 days. in vivo tests are required to determine the effects the modified GPCs as alternative on PMMA in rTKA.

The Role of Poly(Methyl Methacrylate) in Management of Bone Loss and Infection in Revision Total Knee Arthroplasty: A Review.

Poly(methyl methacrylate) (PMMA) is widely used in joint arthroplasty to secure an implant to the host bone. Complications including fracture, bone loss and infection might cause failure of total knee arthroplasty (TKA), resulting in the need for revision total knee arthroplasty (rTKA). The goals of this paper are: (1) to identify the most common complications, outside of sepsis, arising from the application of PMMA following rTKA, (2) to discuss the current applications and drawbacks of employing PMMA in managing bone loss, (3) to review the role of PMMA in addressing bone infection following complications in rTKA. Papers published between 1970 to 2018 have been considered through searching in Springer, Google Scholar, IEEE Xplore, Engineering village, PubMed and weblinks. This review considers the use of PMMA as both a bone void filler and as a spacer material in two-stage revision. To manage bone loss, PMMA is widely used to fill peripheral bone defects whose depth is less than 5 mm and covers less than 50% of the bone surface. Treatment of bone infections with PMMA is mainly for two-stage rTKA where antibiotic-loaded PMMA is inserted as a spacer. This review also shows that using antibiotic-loaded PMMA might cause complications such as toxicity to surrounding tissue, incomplete antibiotic agent release from the PMMA, roughness and bacterial colonization on the surface of PMMA. Although PMMA is the only commercial bone cement used in rTKA, there are concerns associated with using PMMA following rTKA. More research and clinical studies are needed to address these complications.

Novel adhesives for sternal fixation and stabilization: A biomechanical analysis.

BACKGROUND: Cerclage wires remain the current standard of care following median sternotomy, despite significant complications including dehiscence and infection. This study uses a human cadaveric model to investigate the use of glass polyalkenoate cements formulated from two glasses, A (mole fraction: SiO2:0.48, ZnO:0.36, CaO:0.12, SrO:0.04) and B (mole fraction: SiO2:0.48, ZnO:0.355, CaO:0.06, SrO:0.08, P2O5:0.02, Ta2O5:0.005), to improve wired sternal fixation. METHODS: Median sternotomies were performed on fifteen cadaveric sterna. Fixation was performed with either traditional wire cerclage or adhesive-enhanced wire cerclage; the adhesive based on either Glass A or Glass B. Cyclic tensile loading of 10 N to 100 N was applied. Every 30 cycles, the maximum load was increased by 100 N up to a maximum of 500 N. Two adhered sterna were tested beyond 500 N. Mid-sternal displacement was measured to assess fixation stability. FINDINGS: Displacement for adhesive-enhanced sternal closures were significantly less (p < 0.05) than standard wire cerclage. There was no significant difference between adhesives. Up to 500 N, no adhesive-enhanced sternum experienced a pathological sternal displacement (>2 mm), while three out of five of traditional wire fixations did. Of the two adhered samples tested beyond 500 N, one showed pathological displacement at 800 N and the other at 1100 N. Failure of adhered sterna appeared to initiate within the trabecular bone rather than in the adhesive. INTERPRETATION: The adhesives were capable of providing immediate bone stability, significantly reducing sternal displacement. In vivo investigations are warranted to determine the effect the adhesives have on bone remodelling.

The effect of tantalum incorporation on the physical and chemical properties of ternary silicon-calcium-phosphorous mesoporous bioactive glasses.

Synthesis and characterization of the first mesoporous bioactive glasses (MBGs) containing tantalum are reported here, along with their potential application as hemostats. Silica MBGs were synthesized using with the molar composition of (80-x)% Si, 15% Ca, 5% P, and x% Ta. It was found that incorporation of >1 mol % Ta into the MBGs changes their physical and chemical properties. Increasing Ta content from 0 to 10 mol % causes a decrease in the surface area and pore volume of ~20 and ~35%, respectively. This is due to the increase in nonbridging oxygens and mismatch of thermal expansion coefficient which created discontinuities in the ordered channel structure. However, the effect is not significant on the amount of ions (Si, Ca, P, and Ta) released, from the sample into deionized water, for short durations (<60 min). In a mouse tail-cut model, a significant decrease in bleeding time (≥50% of average bleeding time) was found for Ta-MBGs compared to having no treatment, Arista, and MBG without Ta. Further studies are proposed to determine the mechanism of Ta involvement with the hemostatic process. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2229-2237, 2019.

Novel adhesives for distal radius fixation: A biomechanical analysis.

Wrist fractures can be difficult to treat due to advanced age of the patient, medical co-morbidities, and comminution of the bone. This study examines the effectiveness of two injectable glass polyalkenoate cements (GPCs), derived from two different glasses (A and B), as minimally invasive treatments for distal radius fractures. Twenty-seven fresh cadaveric radial pairs were tested either in compressive fatigue or to quasi-static compressive failure. The radii tested to failure had one pair fixated with a GPC while the other was left intact. The radii tested under fatigue had one pair fixated with a GPC and the other with a volar locking plate. A wedge osteotomy was used to simulate a severely comminuted fracture. When loaded to failure, the radii fixated with a GPC made from glass A or B were found to be, respectively, at least 57% and 62% as strong as their intact biological pair (95% Confidence Interval, Lower). Using a paired t-test, the radii fixated with either adhesive were found to be significantly stiffer than their biological pairs fixated with a volar locking plate for all cycles of fatigue loading. The adhesives under investigation demonstrate promise as treatment for distal radius fractures. In vivo investigations are warranted to determine the effect that the adhesives have on the bone remodelling process.

Rapidly-Dissolving Silver-Containing Bioactive Glasses for Cariostatic Applications.

A novel bioactive glass series containing incremental amounts of silver oxide was synthesized, ground down, and subsequently incorporated into a dentifrice for the purpose of reducing the incidence of dental caries and lesion formation. Three glasses were synthesized using the melt quench route: Si-Control (70SiO2-12CaO-3P2O5-15Na2O, mol %), Si-02 and Si-05, where 0.2 and 0.5 mol % Ag2O were substituted, respectively, for SiO2 in Si-Control. The glasses were then ground, sieved, characterized, and dissolved in Tris buffer solution (pH = 7.30) for 6, 12, and 24 h, with the pH of the resultant solution being recorded and the ions that were released into solution quantified. Samples of each glass were subsequently embedded into a non-fluoridated, commercially available toothpaste which was then used to brush resin-mounted lamb molars which, up to the point of testing, had been stored in a 1.0 M HCl solution. Knoop microhardness measurements of the molars were recorded before and after brushing to determine the presence of remineralization on the surface of the teeth (surface hardness loss of 37%, 35%, and 34% for Si-Control, Si-02 and Si-05, respectively, after 24 h). Four oral cavity bacterial strains were isolated through swabs of the inner cheek, gums, and teeth surfaces of three volunteers, and placed on agar discs. Of each glass, 0.5 g was placed onto the discs, and the resultant inhibition zones were measured after 6, 12, and 24 h. Si-05 performed better than Si-02 on two strains after 24 h, while exhibiting similar behavior for the remaining two strains after 24 h; the largest inhibition zone measured was 2.8 mm, for Si-05 after 12 h. Si-Control exhibited no antibacterial effect at any time point, providing evidence for the role of silver oxide as the antibacterial component of these glasses.

Percutaneous upper extremity fracture fixation using a novel glass-based adhesive.

OBJECTIVE: To develop a surgical technique for percutaneous upper extremity fracture fixation using a novel glass-based adhesive. METHODS: Three intact upper extremity cadaveric specimens with undisturbed soft tissues were obtained. Two were used to model a wrist fracture, and the third to model a proximal humerus fracture. Fractures were produced using a small osteotome in a percutaneous fashion. Banna Bone Adhesive (BBA) was delivered to the fracture site percutaneously using a 16 gauge needle under bi-planar fluoroscopic guidance. After setting of the adhesive, the specimens were dissected to qualitatively assess BBA delivery and placement. RESULTS: The adhesive could readily be delivered through the 16 gauge needle with an appropriate amount of pressure applied to the syringe. Using the fluoroscope, the adhesive could be seen to flow into the fracture site with minimal extravagation into the surrounding soft tissues. Successful bonding of the fracture fragments was observed. CONCLUSIONS: Percutaneous delivery of BBA into a fracture of the distal radius and proximal humerus may be a feasible fracture fixation technique. Biomechanical testing and animal model testing are required to further develop this procedure.

A novel tantalum-containing bioglass. Part II. Development of a bioadhesive for sternal fixation and repair.

With over a million median sternotomy surgeries performed worldwide every year, sternal wound complications have posed a serious risk to the affected patients. A rigid therapeutic sternal fixation device has therefore become a necessity. In this work, the incorporation of up to 0.5mol% of tantalum pentoxide (Ta2O5), in exchange for zinc oxide (ZnO), into the SiO2-ZnO-CaO-SrO-P2O5 glass system is presented. The effect of Ta incorporation on the physical, chemical and biological properties of the glass polyalkenoate cements (GPCs) prepared from them have been presented in this manuscript. The data obtained have confirmed that Ta2O5 incorporation into the reference glass system results in increased working times, radiopacity, ion solubility, and long-term mechanical stability. The formulated glass systems have also shown clear antibacterial and antifungal activity against both Gram-negative (Escherichia coli) and Gram-positive prokaryotes (Staphylococcus aureus and Streptococcus epidermidis), as well as eukaryotes (Fusarium solani). Cytotoxicity testing showed that Ta incorporation results in no toxicity effect and may simulate osseo-integration when tested in animal models. These new metallic-containing biomaterial adhesives have been developed for sternal fixation and repair. As a permanent implant, the formulated adhesives can be used in conjunction with sternal cable ties to offer optimal fixation for patients and reduce post-operative complications such as bacterial infection and pain from micro-motion.

A novel tantalum-containing bioglass. Part I. Structure and solubility.

Bioglasses are employed for surgical augmentation in a range of hard tissue applications. Tantalum is a bioactive and biocompatible transition metal that has been used as an orthopedic medical device. It has a range of biological and physical properties that make its incorporation into ionic form into bioactive glass systems promising for various clinical applications. The work herein reports the characterization and properties of novel tantalum-containing glasses. A series of glasses based on the system 48SiO2-(36-X)ZnO-6CaO-8SrO-2P2O5-XTa2O5 with X varying from 0mol% (TA0) to 0.5mol% (TA2) were synthesized. The addition of small amounts of Ta2O5 did not cause crystallization of the glasses but increasing Ta2O5 content at the expense of ZnO was found to result in an increased number of bridging oxygens (BOs). This, along with the data recorded by differential thermal analysis (DTA) and magic angle spinning-nuclear magnetic resonance (MAS-NMR), confirms that Ta acts as a glass former in this series. Solubility experiments showed that minor changes in the glass structure caused by Ta incorporation (0.5mol%) exhibited greater cumulative % weight loss, pH values and cumulative Zn2+ and Sr2+ ion concentration over a period of 30days of maturation, when compared to Ta2O5-free glasses. The results presented in this article confirm that replacing ZnO with Ta2O5 in silicate glasses results in the formation of stronger bonds within the glass network without any adverse effects on the solubility of the glasses prepared from them.

A glass polyalkenoate cement carrier for bone morphogenetic proteins.

This work considers a glass polyalkenoate cement (GPC)-based carrier for the effective delivery of bone morphogenetic proteins (BMPs) at an implantation site. A 0.12 CaO-0.04 SrO-0.36 ZnO-0.48 SiO2 based glass and poly(acrylic acid) (PAA, Mw 213,000) were employed for the fabrication of the GPC. The media used for the water source in the GPC reaction was altered to produce a series of GPCs. The GPC liquid media was either 100 % distilled water with additions of albumin at 0, 2, 5 and 8 wt% of the glass content, 100 % formulation buffer (IFB), and 100 % BMP (150 µg rhBMP-2/ml IFB). Rheological properties, compressive strength, ion release profiles and BMP release were evaluated. Working times (Tw) of the formulated GPCs significantly increased with the addition of 2 % albumin and remained constant with further increases in albumin content or IFB solutions. Setting time (Ts) experienced an increase with 2 and 5 % albumin content, but a decrease with 8 % albumin. Changing the liquid source to IFB containing 5 % albumin had no significant effect on Ts compared to the 8 % albumin-containing BT101. Replacing the albumin with IFB/BMP-2 did not significantly affect Tw. However, Ts increased for the BT101_BMP-2 containing GPCs, compared to all other samples. The compressive strength evaluated 1 day post cement mixing was not affected significantly by the incorporation of BMPs, but the ion release did increase from the cements, particularly for Zn and Sr. The GPCs released BMP after the first day, which decreased in content during the following 6 days. This study has proven that BMPs can be immobilized into GPCs and may result in novel materials for clinical applications.

Comparative study of Weibull characteristic strength and mean strength of GPCs to confirm the minimum number of samples needed for confident strength reporting.

This short communication determines the strength of two glass polyalkenoate cements that differ from each other through the composition of their glass phase. Sample sets of n=5, 10, 20 and 30 were formulated and tested in biaxial flexure. The derived mean for each sample set was compared against the Weibull characteristic strength. The mean and corresponding characteristic strength show a maximum percentage difference 10.1%, and the 95% confidence intervals calculated from the mean data encompass the corresponding characteristic strength down to a sample set of n=5. This suggests that, for brittle materials such as glass polyalkenoate cements, it is acceptable to test only five samples of each material in biaxial flexure and the resultant 95% confidence intervals will encompass the corresponding Weibull characteristic strength of the material.

A review of sternal closure techniques.

Sternotomy and sternal closure occur prior to and post cardiac surgery, respectively. Although post-operative complications associated with poor sternal fixation can result in morbidity, mortality, and considerable resource utilization, sternotomy is preferred over other methods such as lateral thoracotomy. Rigid sternal fixation is associated with stability and reduced incidence of post-operative complications. This is a comprehensive review of the literature evaluating in vivo, in vitro, and clinical responses to applying commercial and experimental surgical tools for sternal fixation after median sternotomy. Wiring, interlocking, plate-screw, and cementation techniques have been examined for closure, but none have experienced widespread adoption. Although all techniques have their advantages, serious post-operative complications were associated with the use of wiring and/or plating techniques in high-risk patients. A fraction of studies have analyzed the use of sternal interlocking systems and only a single study analyzed the effect of using kryptonite cement with wires. Plating and interlocking techniques are superior to wiring in terms of stability and reduced rate of post-operative complications; however, further clinical studies and long-term follow-up are required. The ideal sternal closure should ensure stability, reduced rate of post-operative complications, and a short hospitalization period, alongside cost-effectiveness.

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.