Desaminotyrosyl-tyrosine Ethyl Ester Carbonate Research Articles

Iodination of PEGylated Polymers Counteracts the Inhibition of Fibrinogen Adsorption by PEG.

Poly(ethylene glycol), PEG, known to inhibit protein adsorption, is widely used on the surfaces of biomedical devices when biofilm formation is undesirable. Poly(desaminotyrosyl-tyrosine ethyl ester carbonate), PDTEC, PC for short, has been a promising coating polymer for insertion devices, and it has been anticipated that PEG plays a similar role if it is copolymerized with PC. Earlier studies show that no fibrinogen (Fg) is adsorbed onto PC polymers with PEG beyond the threshold weight percentage. This is attributed to the phase separation of PEG. Further, iodination of the PC units in the PC polymer, (I2PC), has been found to counteract this Fg-repulsive effect by PEG. In this study, we employ surface-sensitive X-ray techniques to demonstrate the surface affinity of Fg toward the air-water interface, particularly in the presence of self-assembled PC-based film, in which its constituent polymer units are assumed to be much more mobile as a free-standing film. Fg is found to form a Gibbs monolayer with its long axis parallel to the aqueous surface, thus maximizing its interactions with hydrophobic interfaces. It influences the amount of insoluble, surface-bound I2PC likely due to the desorption of the formed Fg-I2PC complex and/or the penetration of Fg onto the I2PC film. The results show that the phase behavior at the liquid-polymer interface shall be taken into account for the surface behavior of bulk polymers surrounded by tissue. The ability of PEG units rearranging into a protein-blocking layer, rather than its mere presence in the polymer, is the key to antifouling characteristics desired for polymeric coating on insertion devices.

Researchers Make Advances in Neural Stem Cell Therapy

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessResearchers Make Advances in Neural Stem Cell TherapyNick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:20 May 2016https://doi.org/10.1176/appi.pn.2016.4b19AbstractWith the help of a polymer-based scaffold, researchers may be able to greatly improve the survival and integration of transplanted stem cells in the brain.While there are many therapeutic options for treating psychiatric disorders that involve the improper or insufficient activity of brain cells, such as depression or schizophrenia, treatment can be more difficult in neurodegenerative disorders like Alzheimer’s in which cells die—one cannot repair what no longer exists.Seeding stem cells on a 3-D polymer scaffold (area within the white dashed line) helps them mature, extend, and integrate with surrounding neurons when transplanted into the brain, paving the way for novel therapies to replace cells lost to neurodegeneration.Neal K. BennettOne intriguing research avenue in the field of neurodegeneration involves transplanting new nerve cells into the brain. This still experimental therapy holds potential, but needs to overcome a pair of important hurdles: making enough viable neurons to transplant and ensuring survival once neurons are transplanted.Advances in stem cell technology, notably the ability to generate large amounts of neurons from a patient’s skin cells, are addressing the former issue. A study published March 17 in Nature Communications may help with the latter. Currently, the neuronal transplantation process is a simplistic affair—cultured cells in a liquid solution are injected into the brain with the hopes that they will graft onto some tissue and start growing. The survival rate of such transplanted cells has been very low. In this new study, a research team at Rutgers University increased the survival rate nearly 40-fold by placing the neurons on tiny organic scaffolds prior to their injection; these micro-scaffolds are 3-D structures that recreate a natural environment and enable the stem cells to begin branching out and making connections—forming synapses—with neighbors before the injection process, in short, helping “prime” the stem cells for their maturation.Some work has been done in scaffolding already, seeding cells on gels and protein structures, but these designs have had shortcomings; notably, they can encourage stem cells to proliferate but not necessarily mature into neurons. This unchecked proliferation can increase the risk that transplanted cells will form tumors known as teratomas in the brain.Prabhas Moghe, Ph.D., a distinguished professor of biomedical engineering and chemical engineering at Rutgers, worked with his colleagues to design a scaffold made from a polymer called poly(desaminotyrosyl tyrosine ethyl ester carbonate), or pDTEc, which was spun into a thick, weblike structure. As Moghe noted in a press release, the spaces formed among the criss-crossing polymer fibers is a critical element. “If the scaffolds are too dense, the stem cell–derived neurons are unable to integrate into the scaffold; whereas if they are too sparse, then the network organization tends to be poor since they can’t sense the presence of their neighbors.”After testing various combinations on slices of brain tissue, the team found an ideal configuration and tested it in living mice—with high success. In addition to the 40-fold increase in the survival of the injected cells, biochemical analysis revealed the presence of several proteins involved in the formation of neural synapses, suggesting the transplanted cells were not only growing but also becoming functional brain cells.Moghe’s team is fine-tuning its scaffolding system to specifically develop dopamine-producing neurons for use as a Parkinson’s disease therapy, though there still is a good deal of work left before any human studies can begin. However, they believe that this approach could be adapted to apply to a wide range of brain disorders.This study was supported by grants from the National Institute of Biomedical Imaging and Bioengineering, National Institute of Neurological Disorders and Stroke, National Institute on Alcohol Abuse and Alcoholism, and National Institute on Drug Abuse. ■“Generation and Transplantation of Reprogrammed Human Neurons in the Brain Using 3D Microtopographic Scaffolds” can be accessed here. ISSUES NewArchived

Competitive Adsorption of Plasma Proteins Using a Quartz Crystal Microbalance.

Proteins that get adsorbed onto the surfaces of biomaterials immediately upon their implantation mediate the interactions between the material and the environment. This process, in which proteins in a complex mixture compete for adsorption sites on the surface, is determined by the physicochemical interactions at the interface. Competitive adsorption of bovine serum albumin (BSA), fibronectin (Fn), and collagen type I (Col I), sequentially and from mixtures, was investigated so as to understand the performances of different surfaces used in biomedical applications. A quartz crystal microbalance with dissipation was used to monitor the adsorption of these proteins onto two materials used in functional bone replacement, a titanium alloy (Ti6Al4V) and Ti6Al4V physisorbed with poly(sodium styrenesulfonate) [poly(NaSS)], and three controls, gold, poly(desaminotyrosyltyrosine ethyl ester carbonate) [poly(DTEc)], and polystyrene (PS). In experiments with individual proteins, the adsorption was the highest with Fn and Col I and the least with BSA. Also, protein adsorption was the highest on poly(NaSS) and Ti6Al4V and the least on poly(DTEc). In sequential adsorption experiments, protein exchange was observed in BSA + Fn, Fn + Col I, and BSA + Col I sequences but not in Fn + BSA and Col I + BSA because of the lower affinity of BSA to surfaces relative to Fn and Col I. Protein adsorption was the highest with Col I + Fn on hydrophobic surfaces. In experiments with protein mixtures, with BSA & Fn, Fn appears to be preferentially adsorbed; with Fn & Col I, both proteins were adsorbed, probably as multilayers; and with Col I & BSA, the total amount of protein was the highest, greater than that in sequential and individual adsorption of the two proteins, probably because of the formation of BSA and Col I complexes. Protein conformational changes induced by the adsorbing surfaces, protein-protein interactions, and affinities of proteins appear to be the important factors that govern competitive adsorption. The findings reported here will be useful in understanding the host response to surfaces used for implants.

Structure of biodegradable films at aqueous surfaces: X-ray diffraction and spectroscopy studies of polylactides and tyrosine-derived polycarbonates.

Three representative polymers of increasing modulus, poly(d,l-lactic acid), PDLLA, poly(desaminotyrosyl-tyrosine ethyl ester carbonate), PDTEC, and the same polymer with iodinated DTE segments, PI2DTEC, were characterized by surface-pressure versus area (Π-A) isotherms and surface sensitive X-ray diffraction techniques. Films of 10-100 Å thickness were prepared for these studies by spreading dilute polymer solutions at air-water interfaces. The general properties of the isotherms and the Flory exponents, determined from the isotherms, vary in accordance with the increasing modulus of PDLLA, PDTEC, PI2DTEC, respectively. The analysis of in situ X-ray reflectivity and grazing incidence X-ray diffraction (GIXD) measurements from films at aqueous surfaces provides a morphological picture that is consistent with the modulus of the polymers, and to a large extent, with their packing in their dry-bulk state. Large absorption of X-rays by iodine enabled X-ray spectroscopic studies under near-total-reflection conditions to determine the iodine distribution in the PI2DTEC film and complement the structural model derived from reflectivity and GIXD. These structural studies lay the foundation for future studies of polymer-protein interactions at aqueous interfaces.

Gas-Foamed Scaffold Gradients for Combinatorial Screening in 3D.

Current methods for screening cell-material interactions typically utilize a two-dimensional (2D) culture format where cells are cultured on flat surfaces. However, there is a need for combinatorial and high-throughput screening methods to systematically screen cell-biomaterial interactions in three-dimensional (3D) tissue scaffolds for tissue engineering. Previously, we developed a two-syringe pump approach for making 3D scaffold gradients for use in combinatorial screening of salt-leached scaffolds. Herein, we demonstrate that the two-syringe pump approach can also be used to create scaffold gradients using a gas-foaming approach. Macroporous foams prepared by a gas-foaming technique are commonly used for fabrication of tissue engineering scaffolds due to their high interconnectivity and good mechanical properties. Gas-foamed scaffold gradient libraries were fabricated from two biodegradable tyrosine-derived polycarbonates: poly(desaminotyrosyl-tyrosine ethyl ester carbonate) (pDTEc) and poly(desaminotyrosyl-tyrosine octyl ester carbonate) (pDTOc). The composition of the libraries was assessed with Fourier transform infrared spectroscopy (FTIR) and showed that pDTEc/pDTOc gas-foamed scaffold gradients could be repeatably fabricated. Scanning electron microscopy showed that scaffold morphology was similar between the pDTEc-rich ends and the pDTOc-rich ends of the gradient. These results introduce a method for fabricating gas-foamed polymer scaffold gradients that can be used for combinatorial screening of cell-material interactions in 3D.

The Fiber Diameter of Synthetic Bioresorbable Extracellular Matrix Influences Human Fibroblast Morphology and Fibronectin Matrix Assembly

The ideal scaffold material should provide immediate capacity to bear mechanical loads and also permit eventual resorption and replacement with native tissue of similar mechanical integrity. Scaffold characteristics such as fiber diameter provide environmental cues that can influence cell function and differentiation. In this study, the impact of fiber diameter of scaffolds constructed from a tyrosine-based bioresorbable polymer on cellular response was investigated. Electrospun bioresorbable poly(desamino tyrosyl-tyrosine ethyl ester carbonate) scaffolds composed of microfibers or nanofibers were constructed and seeded with human dermal fibroblasts. The impact of fiber diameter on actin cytoskeletal morphology, focal adhesion size, fibronectin matrix assembly, and cell proliferation was evaluated using immunofluorescent microscopy and computer-assisted image analysis. Actin stress fibers were more easily observed in cells on microfiber scaffolds compared with those on nanofiber scaffolds. Cells on nanofiber scaffolds developed smaller focal adhesion complexes compared with those on microfiber scaffolds (p < 0.0001). The temporal patterns of fibronectin matrix assembly were affected by scaffold fiber diameter, with cells on microfiber scaffolds showing a delayed response in dense fibril formation compared with nanofiber scaffolds. Cells on nanofiber scaffolds showed higher proliferation compared with microfiber scaffolds at time points under 1 week (p < 0.01), but by 2 weeks significantly higher cell proliferation was observed on microfiber scaffolds (p < 0.01). The fiber diameter of bioresorbable scaffolds can significantly influence cell response and suggests that the ability of scaffolds to elicit consistent biological responses depends on factors beyond scaffold composition. Such findings have important implications for the design of clinically useful engineered constructs.

Microphase separation in copolymers of hydrophilic PEG blocks and hydrophobic tyrosine-derived segments using simultaneous SAXS/WAXS/DSC

Hydration- and temperature-induced microphase separations were investigated by simultaneous small- and wide-angle X-ray scattering (SAXS and WAXS) and differential scanning calorimetry (DSC) in a family of copolymers in which hydrophilic poly(ethylene glycol) (PEG) blocks are inserted randomly into a hydrophobic polymer made of either desaminotyrosyl-tyrosine ethyl ester (DTE) or iodinated I2DTE segments. Iodination of the tyrosine rings in I2DTE increased the X-ray contrast between the hydrophobic and hydrophilic segments in addition to facilitating the study of the effect of iodination on microphase separation. The formation of phase-separated, hydrated PEG domains is of considerable significance as it profoundly affects the polymer properties. The copolymers of DTE (or I2DTE) and PEG are a useful model system, and the findings presented here may be applicable to other PEG-containing random copolymers. In copolymers of PEG and DTE and I2DTE, the presence of PEG depressed the glass transition temperature (Tg) of the copolymer relative to the homopolymer, poly(DTE carbonate), and the DTE/I2DTE segments hindered the crystallization of the PEG segments. In the dry state, at large PEG fractions (>70 vol%), the PEG domains self-assembled into an ordered structure with 14–18 nm distance between the domains. These domains gave rise to a SAXS peak at all temperatures in the iodinated polymers, but only above the Tg in non-iodinated polymers, due to the unexpected contrast-match between the crystalline PEG domains and the glassy DTE segments. Irrespective of whether PEG was crystalline or not, immersion of these copolymers in water resulted in the formation of hydrated PEG domains that were 10–20 nm apart. Since both water and the polymer chains must be mobile for the phase separation to occur, the PEG domains disappeared when the water froze, and reappeared as the ice began to melt. This transformation was reversible, and showed hysteresis as did the melting of ice and freezing of the water incorporated into the polymer. PEG–water complexes and PEG–water eutectics were observed in WAXS and DSC scans, respectively.

Impact of Polymer-Bound Iodine on Fibronectin Adsorption and Osteoblast Cell Morphology in Radiopaque Medical Polymers: Tyrosine-Derived Polycarbonate Blends as a Model System

Imaging of polymer implants during surgical implantations is challenging in that most materials lack sufficient X-ray contrast. Synthetic derivatization with iodine serves to increase the scattering contrast but results in distinct physicochemical properties in the material which influence subsequent protein adsorption and cell morphology behavior. Herein we report the impact of increasing iodine inclusion on the cell morphology (cell area and shape) of MC3T3-E1 osteoblasts on a series of homopolymers and discrete blend thin films of poly(desaminotyrosyl tyrosine ethyl ester carbonate), poly(DTE carbonate), and an iodinated analogue poly(I(2)-DTE carbonate). Cell morphology is correlated to film chemical composition via measuring fibronectin (FN) adhesion protein adsorption profile on these films. FN exhibits up to 2-fold greater adsorption affinity for poly(I(2)-DTE carbonate) than (poly(DTE carbonate)). A correlation was established between cell area, roundness, and the measured FN adsorption profile on the blend films up to 75% by mass poly(I(2)-DTE carbonate). Data suggest that incorporation of iodine within the polymer backbone has a distinct impact on the way FN proteins adsorb to the surface and within the studied blend systems; the effect is composition dependent.

Angiogenic competency of biodegradable hydrogels fabricated from polyethylene glycol-crosslinked tyrosine-derived polycarbonates

Synthetic biomaterials can be used as instructive biological milieus to guide cellular behaviour and function. To further realize this application, we synthesized a series of structurally similar hydrogels and tested their ability to modulate angiogenesis. Hydrogels were synthesized from poly(DTE-co-x% DT carbonate) crosslinked by y% poly(ethylene glycol) (PEG). Hydrogel desaminotyrosyl tyrosine (DT) contents (x%) ranged from 10-100%, and crosslink densities (y% PEG-crosslinker) ranged from 5-80%. The hydrogels were fashioned into porous scaffolds with highly interconnected macro- and micro-pore (>100 and 10 mm in diameter, respectively) architecture using poly(DTE-co-10%DT carbonate% crosslinked with 8% PEG. Under physiological conditions (in vitro), the hydrogels degraded into three major products: desaminotyrosyl-tyrosine ethyl ester (DTE), desaminotyrosyl tyrosine (DT), and poly(ethylene glycol)-di-DT-hydrazide (PEG-di-DT hydrazide). Increasing either DT content or crosslink density brought quickened degradation. Because DT and DTE, two of the three major degradation products, have not demonstrated any noticeable cytotoxicity or angiogenic effect in previous studies, we measured the cytotoxicity of PEG-di-DT hydrazide, the third major degradation product. We found that PEG-di-DT hydrazide only displayed significant cytotoxicity at the high concentration of 100 mg/mL. Interestingly, PEG-di-DT hydrazide and its further degradation product PEG-dihydrazide stimulated in vitro endothelial cell migration and tubulogenesis, which is comparable to results found with FGF-beta treatment. Subcutaneous implantation of the PEG-crosslinked poly(DTE-co-10%DT carbonate) scaffolds into the backs of rats elicited greater tissue growth over time and superior vascularization than poly(DTE carbonate) implantation. These results show that this new class of biomaterials has a strong potential to modulate angiogenesis.

Precipitation of a biodegradable polymer using compressed carbon dioxide as antisolvent

Submicronic and micronic particles of a promising biodegradable polymer, poly(desamino tyrosyl-tyrosine ethyl ester carbonate) [poly(DTE carbonate)], were produced by precipitation with compressed carbon dioxide as antisolvent. The effects of temperature, pressure, as well as initial concentration and flow rate of polymer solution on the particle size, size distribution, and morphology were investigated on a lab-scale apparatus with a coaxial injection nozzle. Among these operating parameters, pressure and temperature were found to have only mild effect on the product. Instead, the degree of agglomeration of the products can be manipulated with adjusting the operating parameters. The relationship between the operating variables and the sizes of primary particles reveals that the nature of this polymer is the dominant factor on its solid-state engineering in the course of its precipitation.

X-ray imaging optimization of 3D tissue engineering scaffolds via combinatorial fabrication methods

We have developed a combinatorial method for determining optimum tissue scaffold composition for several X-ray imaging techniques. X-ray radiography and X-ray microcomputed tomography enable non-invasive imaging of implants in vivo and in vitro. However, highly porous polymeric scaffolds do not always possess sufficient X-ray contrast and are therefore difficult to image with X-ray-based techniques. Incorporation of high radiocontrast atoms, such as iodine, into the polymer structure improves X-ray radiopacity but also affects physicochemical properties and material performance. Thus, we have developed a combinatorial library approach to efficiently determine the minimum amount of contrast agent necessary for X-ray-based imaging. The combinatorial approach is demonstrated in a polymer blend scaffold system where X-ray imaging of poly(desaminotyrosyl-tyrosine ethyl ester carbonate) (pDTEc) scaffolds is improved through a controlled composition variation with an iodinated-pDTEc analog (pI 2DTEc). The results show that pDTEc scaffolds must include at least 9%, 16%, 38% or 46% pI 2DTEc (by mass) to enable effective imaging by microradiography, dental radiography, dental radiography through 0.75 cm of muscle tissue or microcomputed tomography, respectively. Only two scaffold libraries were required to determine these minimum pI 2DTEc percentages required for X-ray imaging, which demonstrates the efficiency of this new combinatorial approach for optimizing scaffold formulations.

Fixation of distal femoral osteotomies with self-reinforced polymer/bioactive glass rods: an experimental study on rabbits

Two self-reinforced poly(desamino tyrosyl–tyrosine ethyl ester carbonate), poly(DTE carbonate) or self-reinforced poly(DTE carbonate)/bioactive glass rods, (2 mm by 40 mm) were implanted into the dorsal subcutaneous tissue and osteotomies of the distal femur were fixed with these rods (2 mm by 26 mm) in 36 rabbits. The follow-up times varied from three to 100 weeks. After sacrifice, three-point bending and shear tests and molecular weight measurements were performed for subcutaneously placed rods. Radiological, histological, histomorphometrical, microradiographic, and oxytetracycline-fluorescence studies of the osteotomized and intact control femora were performed. The initial mechanical properties were higher with the SR-poly(DTE carbonate) rods, but the SR-poly(DTE carbonate)/bioactive glass rods lost their mechanical properties slower. At 100 weeks the bending strength had decreased to 21% of the initial value with the SR-poly(DTE carbonate) rods and to 49% with the SR-poly(DTE carbonate)/bioactive glass rods. The shear strength had decreased to 10% with the SR-poly(DTE carbonate) rods and to 23% of the initial value with the SR-poly(DTE carbonate)/bioactive glass rods. Two slight displacements and one delayed union and one failure of fixation were seen in the SR-poly(DTE carbonate) group. In the SR-poly(DTE carbonate)/bioactive glass group five delayed unions and seven slight displacements were seen. No signs of osteolysis or foreign body reactions were observed. Signs of resorption of the implants were seen at 100 weeks in the SR-poly(DTE carbonate)/bioactive glass group. The present investigation showed that the mechanical strength and fixation properties of SR-poly(DTE carbonate) and SR-poly(DTE carbonate)/bioactive glass rods are suitable for fixation of cancellous bone osteotomies in rabbits.

Fixation of distal femoral osteotomies with self-reinforced polymer/bioactive glass rods: an experimental study on rabbits

Two self-reinforced poly(desamino tyrosyl–tyrosine ethyl ester carbonate), poly(DTE carbonate) or self-reinforced poly(DTE carbonate)/bioactive glass rods, (2 mm by 40 mm) were implanted into the dorsal subcutaneous tissue and osteotomies of the distal femur were fixed with these rods (2 mm by 26 mm) in 36 rabbits. The follow-up times varied from three to 100 weeks. After sacrifice, three-point bending and shear tests and molecular weight measurements were performed for subcutaneously placed rods. Radiological, histological, histomorphometrical, microradiographic, and oxytetracycline-fluorescence studies of the osteotomized and intact control femora were performed. The initial mechanical properties were higher with the SR-poly(DTE carbonate) rods, but the SR-poly(DTE carbonate)/bioactive glass rods lost their mechanical properties slower. At 100 weeks the bending strength had decreased to 21% of the initial value with the SR-poly(DTE carbonate) rods and to 49% with the SR-poly(DTE carbonate)/bioactive glass rods. The shear strength had decreased to 10% with the SR-poly(DTE carbonate) rods and to 23% of the initial value with the SR-poly(DTE carbonate)/bioactive glass rods. Two slight displacements and one delayed union and one failure of fixation were seen in the SR-poly(DTE carbonate) group. In the SR-poly(DTE carbonate)/bioactive glass group five delayed unions and seven slight displacements were seen. No signs of osteolysis or foreign body reactions were observed. Signs of resorption of the implants were seen at 100 weeks in the SR-poly(DTE carbonate)/bioactive glass group. The present investigation showed that the mechanical strength and fixation properties of SR-poly(DTE carbonate) and SR-poly(DTE carbonate)/bioactive glass rods are suitable for fixation of cancellous bone osteotomies in rabbits.

Engineered cellular response to scaffold architecture in a rabbit trephine defect.

Tight control of pore architecture in porous scaffolds for bone repair is critical for a fully elucidated tissue response. Solid freeform fabrication (SFF) enables construction of scaffolds with tightly controlled pore architecture. Four types of porous scaffolds were constructed using SFF and evaluated in an 8-mm rabbit trephine defect at 8 and 16 weeks (n = 6): a lactide/glycolide (50:50) copolymer scaffold with 20% w/w tri-calcium phosphate and random porous architecture (Group 1); another identical design made from poly(desaminotyrosyl-tyrosine ethyl ester carbonate) [poly(DTE carbonate)], a tyrosine-derived pseudo-polyamino acid (Group 2); and two poly(DTE carbonate) scaffolds containing 500 microm pores separated by 500-microm thick walls, one type with solid walls (Group 3), and one type with microporous walls (Group 4). A commercially available coralline scaffold (Interpore) with a 486-microm average pore size and empty defects were used as controls. There was no significant difference in the overall amount of bone ingrowth in any of the devices, as found by radiographic analysis, but patterns of bone formation matched the morphology of the scaffold. These results suggest that controlled scaffold architecture can be superimposed on biomaterial composition to design and construct scaffolds with improved fill time.

Fixation of distal femoral osteotomies with self-reinforced poly(desamino tyrosyl–tyrosine ethyl ester carbonate) rods: an experimental study on rats

AbstractSelf-reinforced poly(desamino tyrosyl–tyrosine ethyl ester carbonate) poly(DTE carbonate) rods (diameter, 2 mm; length, 26 mm) were implanted into the dorsal subcutaneous tissue of 16 rats. Osteotomies of the distal femur were fixed with these rods (2mm by 15mm) in 64 other rats. The follow-up times varied from 1 week to 1 year. After sacrifice, three-point bending and shear tests and molecular weight measurements were performed for subcutaneously placed rods. Radiological, histological, histomorphometrical, microradiographic, and oxytetracycline-fluorescence studies of the osteotomized and intact control femurs were performed. At 36 weeks, the bending strength of the rods was nearly at the same level as the initial value, and the shear strength was decreased to about one quarter of the initial value. One of the 64 evaluated osteotomies showed signs of infection at 24 weeks, and there were five failures of fixation. Fifty-eight osteotomies healed uneventfully. No gross signs of inflammatory or foreign-body reactions were observed. The present investigation showed that the mechanical strength and fixation properties of SR-poly(DTE carbonate) rods are suitable for fixation of cancellous bone osteotomies in rats. The present article is the first report on successful application of SR-poly(DTE carbonate) rods for fixation of cancellous bone osteotomies.