Characterization of the conversion of bone cement and borate bioactive glass composites.

Borate bioactive glass 13-93B3 converts into an osteoconductive hydroxyapatite-like material in a liquid medium. In this study, 13-93B3 was incorporated into a commercial PMMA (poly(methyl methacrylate)) bone cement, and the conversion of the glass into a precipitate in solution was investigated with scanning electron microscopy, energy dispersive X-ray spectroscopy, Fourier transform infrared (spectroscopy)-attenuated total reflection, and micro-Raman spectroscopy. Glass particles of 5, 33, and 100 µm diameter were each mixed with the PMMA cement to create 20, 30, and 40% glass-loaded composites. Precipitate formation was found to be a calcium-deficient apatite partially substituted with magnesium ions that resembles native bone material and would ideally encourage bone growth better than stoichiometric hydroxyapatite. Composites of bone cement and 13-93B3 show promise as a means of encouraging bone attachment to the surface of the bone cement.

Mechanical and degradation properties of poly(methyl methacrylate) cement/borate bioactive glass composites.

Bone cement is used extensively in orthopedics to anchor prostheses to bone and fill voids. Incorporating bioactive glass into poly(methyl methacrylate) (PMMA)-based bone cement could potentially improve its effectiveness for these tasks. This study characterizes the mechanical and degradation properties of composites containing PMMA-based bone cement and particles of borate bioactive glass designated as 13-93B3. Glass particles of size 5, 33, and 100 µm were mixed with PMMA bone cement to create composites containing 20, 30, and 40 wt % glass. Composites and a bone cement control were soaked in phosphate-buffered saline. Compressive strength, Young's modulus, weight loss, water uptake, solution pH, and ionic concentrations were measured over 21 days. The compressive strengths of composites decreased over 21 days. Average Young's moduli of the composites remained below 3 GPa. Weight loss and water uptake of specimens did not exceed 2 and 6%, respectively. Boron concentrations and pH of all solutions increased over time, with higher glass weight fractions leading to higher pH values. Results demonstrated that the composite can sustain glass degradation and ionic release without compromising short-term mechanical strength.

Remodeling of injectable, low-viscosity polymer/ceramic bone grafts in a sheep femoral defect model.

Ceramic/polymer composite bone grafts offer the potential advantage of combining the osteoconductivity of ceramic component with the ductility of polymeric component, resulting in a graft that meets many of the desired properties for bone void fillers (BVF). However, the relative contributions of the polymer and ceramic components to bone healing are not well understood. In this study, we compared remodeling of low-viscosity (LV) ceramic/poly(ester urethane) composites to a ceramic BVF control in a sheep femoral condyle plug defect model. LV composites incorporating either ceramic (LV/CM) or allograft bone (LV/A) particles were evaluated. We hypothesized that LV/CM composites which have the advantageous handling properties of injectability, flowability, and settability would heal comparably to the CM control, which was evaluated for up to 2 years to study its long-term degradation properties. Remodeling of LV/CM was comparable to that observed for the CM control, as evidenced by new bone formation on the surface of the ceramic particles. At early time points (4 months), LV/CM composites healed similar to the ceramic clinical control, while LV/A components showed more variable healing due to osteoclast-mediated resorption of the allograft particles. At longer time points (12-15 months), healing of LV/CM composites was more variable due to the nonhomogeneous distribution and lower concentration of the ceramic particles compared to the ceramic clinical control. Resorption of the ceramic particles was almost complete at 2 years. This study highlights the importance of optimizing the loading and distribution of ceramic particles in polymer/ceramic composites to maximize bone healing. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2333-2343, 2017.

Apatite formation on a hydrogel containing sulfinic acid group under physiological conditions.

Natural bone consists of apatite and collagen fiber. Bioactive materials capable to bonding to bone tissue are clinically used as bone-repairing materials. Apatite-organic polymer composites exhibit bone-bonding abilities and mechanical properties similar to those of natural bone, and these materials can be prepared using biomimetic processes in simulated body fluid (SBF). Specific functional groups such as sulfonic and carboxylic acid groups are known to induce the heterogeneous nucleation of apatite in SBF. However, it remains unclear whether structurally related sulfinic acid groups can contribute to apatite formation in the same way, despite sodium sulfonate being used in biomedical applications as a radical polymerization promoter in adhesive dental resin. Herein, we report the preparation of a new hydrogel containing sulfinic acid groups from sodium 4-vinylbenzenesulfinate and 2-hydroxyethyl methacrylate using a radical polymerization reaction and the subsequent incorporation of Ca2+ ions into this material. We also investigated the apatite-forming behavior of these hydrogels in SBF. Hydrogels containing sulfinic acid groups showed higher apatite-forming ability than those without sulfinic acid groups. In addition, the apatite layer formed on the former showed tight adhesion to the hydrogel. This phenomenon was attributed to the heterogeneous nucleation of apatite, induced by the sulfinic acid groups. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1924-1929, 2017.

Effect of hydroxyapatite concentration on high-modulus composite for biodegradable bone-fixation devices.

There are over 3 million bone fractures in the United States annually; over 30% of which require internal mechanical fixation devices to aid in the healing process. The current standard material used is a metal plate that is implanted onto the bone. However, metal fixation devices have many disadvantages, namely stress shielding and metal ion leaching. This study aims to fix these problems of metal implants by making a completely biodegradable material that will have a high modulus and exhibit great toughness. To accomplish this, long-fiber poly-l-lactic acid (PLLA) was utilized in combination with a matrix composed of polycaprolactone (PCL) and hydroxyapatite (HA) nano-rods. Through single fibril tensile tests, it was found that the PLLA fibers have a Young's modulus of 8.09 GPa. Synthesized HA nanorods have dimensions in the nanometer range with an aspect ratio over 6. By dip coating PLLA fibers in a suspension of PCL and HA and hot pressing the resulting coated fibers, dense fiber-reinforced samples were made having a flexural modulus up to 9.2 GPa and a flexural strength up to 187 MPa. The flexural modulus of cortical bone ranges from 7 to 25 GPa, so the modulus of the composite material falls into the range of bone. The typical flextural strength of bone is 130 MPa, and the samples here greatly exceed that with a strength of 187 MPa. After mechanical testing to failure the samples retained their shape, showing toughness with no catastrophic failure, indicating the possibility for use as a fixation material. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1963-1971, 2017.

Oleic acid surfactant in polycaprolactone/hydroxyapatite-composites for bone tissue engineering.

Bone substitutes are required to repair osseous defects caused by a number of factors, such as traumas, degenerative diseases, and cancer. Autologous bone grafting is typically used to bridge bone defects, but suffers from chronic pain at the donor-site and limited availability of graft material. Tissue engineering approaches are being investigated as viable alternatives, which ideal scaffold should be biocompatible, biodegradable, and promote cellular interactions and tissue development, need to present proper mechanical and physical properties. In this study, poly(ε-caprolactone) (PCL), oleic acid (OA) and hydroxyapatite (HAp) were used to obtain films whose properties were investigated by contact angle, scanning electron microscopy, atomic force microscopy, tensile mechanical tests, and in vitro tests with U2OS human osteosarcoma cells by direct contact. Our results indicate that by using OA as surfactant/dispersant, it was possible to obtain a homogenous film with HAp. The PCL/OA/Hap sample had twice the roughness of the control (PCL) and a lower contact angle, indicating increased hydrophilicity of the film. Furthermore, mechanical testing showed that the addition of HAp decreased the load at yield point and tensile strength and increased tensile modulus, indicating a more brittle composition vs. PCL matrix. Preliminary cell culture experiments carried out with the films demonstrated that U2OS cells adhered and proliferated on all surfaces. The data demonstrate the improved dispersion of HAp using OA and the important consequences of this addition on the composite, unveiling the potentially of this composition for bone growth support. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1076-1082, 2016.

In vitro evaluation of thermal frontally polymerized thiol-ene composites as bone augments.

Because of the large number of total knee replacement (TKR) surgeries conducted per year, and with projections of increased demand to almost a million primary TKR surgeries per year by 2030 in the United States alone, there is a need to discover more efficient working materials as alternatives to current bone cements. There is a need for surgeons and hospitals to become more efficient and better control over the operative environment. One area of inefficiency is the cement steps during TKR. Currently the surgeon has very little control over cement polymerization. This leads to an increase in time, waste, and procedural inefficiencies. There is a clear need to create an extended working time, moldable, osteoconductive, and osteoinductive bone augment as a substitution for the current clinically used bone cement where the surgeon has better control over the polymerization process. This study explored several compositions of pentaerythritol-co-trimethylolpropane tris-(3-mercaptopropionate) hydroxyapatite composite materials prepared via benzoyl peroxide-initiated thermal frontal polymerization. The 4:1 acrylate to thiol ratio containing augment material shows promise with a maximal propagation temperature of 160°C ± 10°C, with mechanical strength of 3.65 MPa, and 111% cytocompatibility, relative to the positive control. This frontally polymerized material may have application as an augment with controlled polymerization supporting cemented implants. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1152-1160, 2016.

Effect of the preparation methods on architecture, crystallinity, hydrolytic degradation, bioactivity, and biocompatibility of PCL/bioglass composite scaffolds.

In this study, two different composition gel derived silica-rich (S2) or calcium-rich (A2) bioactive glasses (SBG) from a basic CaO-P2 O5 -SiO2 system were incorporated into poly(ε-caprolactone) (PCL) matrix to obtain novel bioactive composite scaffolds for bone tissue engineering applications. The composites were fabricated in the form of highly porous 3D scaffolds using following preparation methods: solvent casting particulate leaching (SCPL), solid-liquid phase separation, phase inversion (PI). Scaffolds containing 21% vol. of each bioactive glass were characterized for architecture, crystallinity, hydrolytic degradation, surface bioactivity, and cellular response. Results indicated that the use of different preparation methods leads to obtain highly porous (60-90%) materials with differentiated morphology: pore shape, size, and distributions. Thermal analysis (DSC) showed that the preparation method of materials and addition of bioactive glass particles into polymer matrix induced the changes of PCL crystallinity. Composites obtained by SCPL and PI method containing A2 SBG rapidly formed a hydroxyapatite calcium phosphate surface layer after incubation in SBF. Bioactive glasses used as filler in composite scaffolds could neutralize the released acidic by-products of the polymer degradation. Preliminary in vitro biological studies of the composites in contact with osteoblastic cells showed good biocompatibility of the obtained materials. Addition of bioactive glass into the PCL matrix promotes mineralization estimated on the basis of the ALP activity. These results suggest that through a process of selection appropriate methods of preparation and bioglass composition it is possible to design and obtain porous materials with suitable properties for regeneration of bone tissue.

Injectable radiopaque and bioactive polycaprolactone-ceramic composites for orthopedic augmentation.

The aim of this study was to develop and characterize an injectable bone void filler by incorporating baghdadite (Ca3 ZrSi2 O9 ) particles (average size of 1.7 µm) into polycaprolactone (PCL). A series of PCL composites containing different volume percentages of baghdadite [1 (PCL-1%Bag), 5 (PCL-5%Bag), 10 (PCL-10%Bag), 20 (PCL-20%Bag), and 30 (PCL-30%Bag)] were prepared, and their injectability, setting time, mechanical properties, radiopacity, degradation, and cytocompatibility were investigated. PCL, PCL-1%Bag, PCL-5%Bag, and PCL-10%Bag were able to be injected through a stainless steel syringe (Length: 9.0 mm, nozzle diameter: 2.2 mm) at 75°C at injection forces of below 1.5 kN. The core temperature of the injected material at the nozzle exit ranged between 55 and 60°C and was shown to set after 2.5-3.5 min postinjection in a 37°C environment. Injection force, melt viscosity, and radiopacity of the composites increased with increasing baghdadite content. Incorporation of 10-30 vol % baghdadite into PCL increased the compressive strength of the composites from 36 to 47.1 MPa, compared with that for pure PCL (31.4 MPa). Similar trend was found for the compressive modulus of the composites, which increased from 203.8 to 741 MPa, compared with that for pure PCL (205 MPa). Flexural strain of PCL, PCL-5%Bag, and PCL-10%Bag exceeded 30%, and PCL-10%Bag showed the highest flexural strength (29.8 MPa). Primary human osteoblasts cultured on PCL-10%Bag showed a significant upregulation of osteogenic genes compared with pure PCL. In summary, our results demonstrated that PCL-10%Bag could be a promising injectable material for orthopedic and trauma application.

Effects of particle size and porosity on in vivo remodeling of settable allograft bone/polymer composites.

Established clinical approaches to treat bone voids include the implantation of autograft or allograft bone, ceramics, and other bone void fillers (BVFs). Composites prepared from lysine-derived polyurethanes and allograft bone can be injected as a reactive liquid and set to yield BVFs with mechanical strength comparable to trabecular bone. In this study, we investigated the effects of porosity, allograft particle size, and matrix mineralization on remodeling of injectable and settable allograft/polymer composites in a rabbit femoral condyle plug defect model. Both low viscosity and high viscosity grafts incorporating small (<105 µm) particles only partially healed at 12 weeks, and the addition of 10% demineralized bone matrix did not enhance healing. In contrast, composite grafts with large (105-500 µm) allograft particles healed at 12 weeks postimplantation, as evidenced by radial µCT and histomorphometric analysis. This study highlights particle size and surface connectivity as influential parameters regulating the remodeling of composite bone scaffolds.

Reinforced Portland cement porous scaffolds for load-bearing bone tissue engineering applications.

Modified Portland cement porous scaffolds with suitable characteristics for load-bearing bone tissue engineering applications were manufactured by combining the particulate leaching and foaming methods. Non-crosslinked polydimethylsiloxane was evaluated as a potential reinforcing material. The scaffolds presented average porosities between 70 and 80% with mean pore sizes ranging from 300 µm up to 5.0 mm. Non-reinforced scaffolds presented compressive strengths and elastic modulus values of 2.6 and 245 MPa, respectively, whereas reinforced scaffolds exhibited 4.2 and 443 MPa, respectively, an increase of ∼62 and 80%. Portland cement scaffolds supported human osteoblast-like cell adhesion, spreading, and propagation (t = 1-28 days). Cell metabolism and alkaline phosphatase activity were found to be enhanced at longer culture intervals (t ≥ 14 days). These results suggest the possibility of obtaining strong and biocompatible scaffolds for bone repair applications from inexpensive, yet technologically advanced materials such as Portland cement.