Physico-Chemical Characteristics and Posterolateral Fusion Performance of Biphasic Calcium Phosphate with Submicron Needle-Shaped Surface Topography Combined with a Novel Polymer Binder.

A biphasic calcium phosphate with submicron needle-shaped surface topography combined with a novel polyethylene glycol/polylactic acid triblock copolymer binder (BCP-EP) was investigated in this study. This study aims to evaluate the composition, degradation mechanism and bioactivity of BCP-EP in vitro, and its in vivo performance as an autograft bone graft (ABG) extender in a rabbit Posterolateral Fusion (PLF) model. The characterization of BCP-EP and its in vitro degradation products showed that the binder hydrolyses rapidly into lactic acid, lactide oligomers and unaltered PEG (polyethylene glycol) without altering the BCP granules and their characteristic submicron needle-shaped surface topography. The bioactivity of BCP-EP after immersion in SBF revealed a progressive surface mineralization. In vivo, BCP-EP was assessed in a rabbit PLF model by radiography, manual palpation, histology and histomorphometry up to 12 weeks post-implantation. Twenty skeletally mature New Zealand (NZ) White Rabbits underwent single-level intertransverse process PLF surgery at L4/5 using (1) autologous bone graft (ABG) alone or (2) by mixing in a 1:1 ratio with BCP-EP (BCP-EP/ABG). After 3 days of implantation, histology showed the BCP granules were in direct contact with tissues and cells. After 12 weeks, material resorption and mature bone formation were observed, which resulted in solid fusion between the two transverse processes, following all assessment methods. BCP-EP/ABG showed comparable fusion rates with ABG at 12 weeks, and no graft migration or adverse reaction were noted at the implantation site nor in distant organs.

Calcium phosphate cement reinforced with poly (vinyl alcohol) fibers: An experimental and numerical failure analysis.

Calcium phosphate cements (CPCs) have been widely used during the past decades as biocompatible bone substitution in maxillofacial, oral and orthopedic surgery. CPCs are injectable and are chemically resemblant to the mineral phase of native bone. Nevertheless, their low fracture toughness and high brittleness reduce their clinical applicability to weakly loaded bones. Reinforcement of CPC matrix with polymeric fibers can overcome these mechanical drawbacks and significantly enhance their toughness and strength. Such fiber-reinforced calcium phosphate cements (FRCPCs) have the potential to act as advanced bone substitute in load-bearing anatomical sites. This work achieves integrated experimental and numerical characterization of the mechanical properties of FRCPCs under bending and tensile loading. To this end, a 3-D numerical gradient enhanced damage model combined with a dimensionally-reduced fiber model are employed to develop a computational model for material characterization and to simulate the failure process of fiber-reinforced CPC matrix based on experimental data. In addition, an advanced interfacial constitutive law, derived from micromechanical pull-out tests, is used to represent the interaction between the polymeric fiber and CPC matrix. The presented computational model is successfully validated with the experimental results and offers a firm basis for further investigations on the development of numerical and experimental analysis of fiber-reinforced bone cements.

Micro- and macromechanical characterization of the influence of surface-modification of poly(vinyl alcohol) fibers on the reinforcement of calcium phosphate cements.

Calcium phosphate cements (CPCs) are frequently used as synthetic bone substitute materials due to their favorable osteocompatibility and handling properties. However, CPCs alone are inherently brittle and exhibit low strength and toughness, which restricts their clinical applicability to non-load bearing sites. Mechanical reinforcement of CPCs using fibers has proven to be an effective strategy to toughen these cements by transferring stress from the matrix to the fibers through frictional sliding at the interface. Therefore, tailoring the fiber-matrix affinity is paramount in designing highly toughened CPCs. However, the mechanistic correlation between this interaction and the macromechanical properties of fiber-reinforced CPCs has hardly been investigated to date. The aim of this study was to tailor the fiber-matrix interface affinity by modifying the surface of poly(vinyl alcohol) (PVA) fibers and correlate their interfacial properties to macromechanical properties (i.e. fracture toughness, work-of-fracture and tensile strength) of CPCs. Results from single fiber pullout tests reveal that the surface modification of PVA fibers increased their hydrophilicity and improved their affinity to the CPC matrix. This observation was evidenced by an increase in the interfacial shear strength and a reduction in the critical fiber embedment length (i.e. maximum embedded length from which a fiber can be pulled out without rupture). This increased interface affinity facilitated energy dissipation during fracture of CPCs subjected to macromechanical three-point flexure and tensile tests. The fracture toughness also significantly improved, even for CPCs reinforced with fibers of lengths greater than their critical fiber embedment length, suggesting that other crack-arresting mechanisms also play an important role in mechanically reinforcing CPCs. Overall, these basic insights will improve the understanding of the correlation between micro- and macromechanical characteristics of fiber-reinforced CPCs.

Experimental and numerical analysis on bending and tensile failure behavior of calcium phosphate cements.

Since their discovery in the 1980s, injectable self-setting calcium phosphate cements (CPCs) are frequently used in orthopedic, oral and maxillofacial surgery due to their chemical resemblance to the mineral phase of native bone. However, these cements are very brittle, which complicates their application in load-bearing anatomical sites. Polymeric fibers can be used to transform brittle calcium phosphate cements into ductile and load-bearing biomaterials. To understand and optimize this process of fiber reinforcement, it is essential to characterize the mechanical properties of fiber-free calcium phosphate matrices in full detail. However, the mechanical performance of calcium phosphate cements is usually tested under compression only, whereas bending and tensile tests are hardly performed due to technical limitations. In addition, computational models describing failure behavior of calcium phosphate cements under these clinically more relevant loading scenarios have not yet been developed. Here, we investigate the failure behavior of calcium phosphate cements under bending and tensile loading by combining, for the first time, experimental tests and numerical modeling. To this end, a 3-D gradient-enhanced damage model is developed in a finite element framework, and numerical results are correlated to experimental three-point bending and tensile tests to characterize the mechanical properties of calcium phosphate cements in full detail. The presented computational model is successfully validated against experimental results and is able to predict the mechanical response of calcium phosphate cement under different types of loading with a unique set of parameters. This model offers a solid basis for further experimental and computational studies on the development of load-bearing bone cements.

Sterilization effects on the handling and degradation properties of calcium phosphate cements containing poly (D,L -lactic-co-glycolic acid) porogens and carboxymethyl cellulose.

Injectable, self-setting calcium phosphate cements (CPCs) are synthetic bone substitutes considered favorable for the repair and regeneration of bone due to their osteocompatibility and unique handling properties. However, their clinical applicability can be compromised due to insufficient cohesion upon injection into the body coupled with poor degradation rates that restricts new bone formation. Consequently, carboxymethyl cellulose (CMC) was incorporated into CPC formulations to improve their cohesion and injectability while poly (D,L -lactic-co-glycolic acid) (PLGA) porogens were added to introduce macroporosity and improve their biodegradation rate. Like most biomaterials, CPCs are gamma irradiated before clinical use to ensure sufficient sterilization. However, it is well known that gamma irradiation also reduces the molecular weight of CMC and PLGA via chain scission, which affects their material properties. Therefore, the aim of this study is to measure the effect that gamma irradiation has on the molecular weight of CMC at varying doses of 15, 40, or 80 kGy and investigate how this affects the handling (i.e., injectability, cohesion, washout, and setting times) and in vitro degradation behavior of CPC formulations. Results reveal that the molecular weight of CMC decreases with increasing gamma irradiation dose, thereby reducing the viscosifying capabilities of CMC, which causes CPCs to deteriorate more readily. Further, the addition of CMC seems to inhibit the degree of phase transformation during cement setting while the subsequent reduction in molecular weight of PLGA after gamma irradiation improves the in vitro degradation rate of CPCs due to the faster degradation rate of low molecular weight PLGA. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2216-2228, 2019.

Tough and Osteocompatible Calcium Phosphate Cements Reinforced with Poly(vinyl alcohol) Fibers.

Injectable, self-setting calcium phosphate cements (CPCs) are favorable bone substitutes due to their osteocompatibility. However, due to their brittleness and low toughness, their clinical application is limited to non-load-bearing sites. The incorporation of poly(vinyl alcohol) (PVA) fibers into cementitious materials is a successful strategy in civil engineering for improving the mechanical performance of cements. However, PVA fibers in particular have not yet been applied to reinforce CPCs. Therefore, the aim of this study is to investigate the effect of PVA fibers on the mechanical properties of CPCs. Second, the in vitro cytocompatibility of these fibers is studied using cell culture tests. Finally, the in vivo osteocompatibility of PVA fiber-reinforced CPCs is studied after a 6 and 12 week implantation period in the femoral condyle of rabbits. Results reveal that the incorporation of PVA fibers into CPCs is a highly effective strategy to strengthen and toughen CPCs, since the flexural strength and toughness of CPCs increased by more than 3-fold and 435-fold, respectively, upon reinforcement with PVA fibers. In vitro cytocompatibility tests indicate that PVA fibers are cytocompatible, which is further confirmed by the in vivo results that show that PVA fibers do not compromise the excellent osteocompatibility of CPCs.

Surface functionalization of polylactic acid fibers with alendronate groups does not improve the mechanical properties of fiber-reinforced calcium phosphate cements.

Calcium phosphate cements (CPCs) are frequently used as synthetic bone substitute, but their intrinsic low fracture toughness impedes their application in highly loaded skeletal sites. However, fibers can be used to reduce the brittleness of these CPCs provided that the affinity between the fibers and cement matrix facilitates the transfer of loads from the matrix to the fibers. The aim of the present work was to improve the interface between hydrophobic polylactic acid (PLA) microfibers and hydrophilic CPC. To this end, calcium-binding alendronate groups were conjugated onto the surface of PLA microfibers via different strategies to immobilize a tunable amount of alendronate onto the fiber surface. CPCs reinforced with PLA fibers revealed toughness values which were up to 50-fold higher than unreinforced CPCs. Nevertheless, surface functionalization of PLA microfibers with alendronate groups did not improve the mechanical properties of fiber-reinforced CPCs.

Long-term evaluation of the degradation behavior of three apatite-forming calcium phosphate cements.

Calcium phosphate cements (CPCs) are injectable bone substitutes with a long clinical history because of their biocompatibility and osteoconductivity. Nevertheless, their cohesion upon injection into perfused bone defects as well as their long-term degradation behavior remain major clinical challenges. Therefore, the long-term degradation behavior of two types of α-tricalcium phosphate-based, apatite-forming CPCs was compared to a commercially available apatite-forming cement, that is HydroSet™ . Carboxyl methylcellulose (CMC) was used as cohesion promotor to improve handling properties of the two experimental cements, whereas poly (d, l-lactic-co-glycolic) acid (PLGA) microparticles were added to introduce macroporosity and stimulate CPC degradation. All three CPCs were injected into defects drilled into rabbit femoral condyles and explanted after 4, 12, or 26 weeks, after which the bone response was assessed both qualitatively and quantitatively. CPCs without PLGA microparticles degraded only at the periphery of the implants, while the residual CPC volume was close to 90%. On the contrary, bone ingrowth was observed not only at the periphery of the CPC, but also throughout the center of the implants after 26 weeks of implantation for the PLGA-containing CPCs with a residual CPC volume of approximately 55%. In conclusion, it was shown that CPC containing CMC and PLGA was able to induce partial degradation of apatite-forming CPCs and concomitant replacement by bone tissue.

Fill volume as an indicator of surface heterogeneity in glass vials for parenteral packaging.

The chemical durability of glass vials for parenteral packaging is typically assessed by completely filling the vial with a medium of interest. This testing approach can mask the heterogeneous dissolution behavior of vials produced by conversion of glass tubing. In this study, the corrosion behavior of vials provided by four suppliers was evaluated as a function of fill volume. Vials were filled with incrementally increasing volumes of water for injection (WFI) up to near-maximum capacity and then autoclaved. The pH and levels of extracted ions were measured. The pH of autoclaved WFI generally increased for low fill volumes relative to pure WFI, presumably because of extraction of alkali from the heel region. The pH was found to generally decrease with increasing fill volume as the concentration of extractables was diluted. Analysis of dissolution profiles supports the altered surface chemistry of the heel region relative to the body. The results of this study demonstrate the potential limitations of conventional hydrolytic resistance tests and the susceptibility of the heel region to aqueous corrosion.

Designing high-performance electrochemical energy-storage nanoarchitectures to balance rate and capacity.

The impressive specific capacitance and high-rate performance reported for many nanometric charge-storing films on planar substrates cannot impact a technology space beyond microdevices unless such performance translates into a macroscale form factor. In this report, we explore how the nanoscale-to-macroscale properties of the electrode architecture (pore size/distribution, void volume, thickness) define energy and power performance when scaled to technologically relevant dimensions. Our test bed is a device-ready electrode architecture in which scalable, manufacturable carbon nanofoam papers with tunable pore sizes (5-200 nm) and thickness (100-300 µm) are painted with ~10 nm coatings of manganese oxide (MnOx). The quantity of capacitance and the rate at which it is delivered for four different MnOx-C variants was assessed by fabricating symmetric electrochemical capacitors using a concentrated aqueous electrolyte. Carbon nanofoam papers containing primarily 10-20 nm mesopores support high MnOx loadings (60 wt%) and device-level capacitance (30 F g(-1)), but the small mesoporous network hinders electrolyte transport and the low void volume restricts the quantity of charge-compensating ions within the electrode, making the full capacitance only accessible at slow rates (5 mV s(-1)). Carbon nanofoam papers with macropores (100-200 nm) facilitate high rate operation (50 mV s(-1)), but deliver significantly lower device capacitance (13 F g(-1)) as a result of lower MnOx loadings (41 wt%). Devices comprising MnOx-carbon nanofoams with interconnecting networks of meso- and macropores balance capacitance and rate performance, delivering 33 F g(-1) at 5 mV s(-1) and 23 F g(-1) at 50 mV s(-1). The use of carbon nanofoam papers with size-tunable pore structures and thickness provides the opportunity to engineer the electrode architecture to deliver scalable quantities of capacitance (F cm(-2)) in tens of seconds with a single device.