Hydrogels for site-specific oral drug delivery: synthesis and characterization.

Novel types of hydrogels based on hydrophilic N-substituted (meth)acrylamides, N-tert-butylacrylamide and acrylic acid cross-linked with 4,4'-di(methacryloylamino)azobenzene were synthesized. The gels were characterized by the equilibrium degree of swelling as a function of pH, modulus of elasticity in compression at pH 2 and 7.4 and permeability of insulin at pH 2 and 7.4. It was found that the structure of the polymer backbone influenced the pH-dependent swelling. In all cases, the degree of swelling was lower at pH 2 than at 7.4. As the degree of swelling decreased, the modulus of elasticity was found to increase and the permeability of insulin decreased. These gels are enzymatically degradable by microbial azoreductases present in the colon and have a potential use in site-specific drug delivery to the colon.     

Fibril formation pH controls intrafibrillar collagen biomineralization in vitro and in vivo

We demonstrate that intrafibrillar, homogenous collagen biomineralization can be achieved by controlling self-assembly under mildly alkaline conditions. Using dense collagen (DC) gels as an osteoid model, we modulated their fibrillogenesis environment to evaluate the effects of fibrillogenesis pH on the protein charge distribution and ultimately on biomineralization. Cationic and anionic dye staining and electron cryomicroscopy analyses established that fibrillogenesis under mildly alkaline conditions promotes the formation of electronegative charges within the protein (anionic DC gels). These charges are stable upon titration of the gel pH to physiological values. Subsequent exposure of anionic DC gels to simulated body fluid induced the intrafibrillar biomineralization of the gels, promoting a rapid, extensive formation of carbonated hydroxyapatite, and strongly impacting gel mechanical properties. The generality and significance of this approach has been addressed by implanting freshly made anionic DC gels in vivo, in a rat subcutaneous model. Subcutaneous implants showed an extensive, homogenous biomineralization as early as at day 7, indicating that anionic collagen gels rapidly self-mineralize upon contact with body fluids in a non-osseous implantation site. The control of collagen fibrillogenesis pH provides not only new interpretations to what has been called the collagen mineralization enigma by demonstrating that neat collagen can intrafibrilarly self-mineralize, but it will also set a new starting point for the use of DC gels in bone regenerative medicine, in addition as potential applications as mineralized tissue model or as slow-release delivery carriers.     

Dendrimer crosslinked collagen as a corneal tissue engineering scaffold: mechanical properties and corneal epithelial cell interactions

Generation 2 polypropyleneimine octaamine dendrimers were used to generate highly crosslinked collagen with mechanical properties that would make it appropriate for use as a corneal tissue-engineering scaffold. Crosslinking of a highly concentrated collagen solution (2-4%) was effected using the water-soluble carbodiimide 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride (EDC). The multifunctional dendrimers were introduced as novel multifunctional crosslinkers after the activation of the carboxylic acid groups of glutamic and aspartic acid residues in collagen. Glutaraldehyde, a common collagen crosslinker, was used as comparison, as was EDC, itself an alternative crosslinker, which forms "zero-length or self-crosslinking". The mechanical properties resultant gels were determined. Young's modulus of the dendrimer crosslinked gels was significantly higher than that observed with the other crosslinkers, increasing to 5 MPa compared with 0.1 MPa for the EDC crosslinked gels. Transmission electron microscopy (TEM) analysis of the gels demonstrated the presence of fibrils in the thermally gelled collagen controls; no fibrils were observed in the dendrimer crosslinked gels. As a result, the optical transparency of the dendrimer crosslinked collagen was significantly better than that of the collagen thermal gels. The EDC and glutaraldehyde crosslinked gels were generally less transparent than those crosslinked with the dendrimers. Glucose permeation results demonstrated that the dendrimer crosslinked collagen had higher glucose permeability than natural human cornea. Dendrimer crosslinked collagen gels supported human corneal epithelial cell growth and adhesion, with no cell toxicity. In comparison, some potentially cytotoxic effects were observed with glutaraldehyde crosslinked collagen. Overall, the dendrimer crosslinked collagen gels showed promising properties that suggest that these might be suitable scaffolds for corneal tissue engineering and potentially other tissue engineering applications.     

Collagen-silica hybrid materials: sodium silicate and sodium chloride effects on type I collagen fibrillogenesis

Collagen-silica hybrid materials have been considered for potential biomedical applications. Understanding of the collagen-silica interactions is the key to control hybrids structure and properties. For this purpose, the effect of sodium silicate and sodium chloride addition at two concentrations, 0.83 and 10 mM, on the kinetic of the type I collagen fibrillogenesis at 20 degrees C, and pH 7.4 were studied. Absorbance profiles of fibrillogenesis experiments were collected together with measures of silicic acid concentration and transmission electron microscopy analysis. The specific effect of silica addition on the collagen fibrils self-assembly mechanisms was demonstrated by comparison with the sodium chloride. Sodium silicate at 10 mM inhibited the collagen fibrillogenesis. At the same concentration, the sodium chloride decreased the rate of the collagen fibril assembly. Collagen fibrillogenesis kinetic was not significantly disturbed by the presence of 0.83 mM of sodium chloride. However, the same concentration of sodium silicate modified the collagen fibrillogenesis kinetic. Transmission electron microscopy indicated for experiment with 0.83 mM of sodium silicate, the formation of longer and wider fibrils than for the equivalent collagen fibrillogenesis experiment with sodium chloride. The effect of sodium chloride is explained in terms of osmotic exclusion and influence on electrostatic interactions between collagen fibrils. The specific involvement of silicic acid in collagen helices hydrogen-bond interactions is suggested. Finally, the results of this study are discussed regarding the preparation of composites by co-gelation of type I collagen and sodium silicate, for potential application as bone repair device.     

Genipin-induced changes in collagen gels: correlation of mechanical properties to fluorescence

Controlled crosslinking of collagen gels has important applications in cell and tissue mechanics as well as tissue engineering. Genipin is a natural plant extract that has been shown to crosslink biological tissues and to produce color and fluorescence changes upon crosslinking. We have characterized the effects of genipin concentration and incubation duration on the mechanical and fluorigenic properties of type I collagen gels. Gels were exposed to genipin (0, 1, 5, or 10 mM) for a defined duration (2, 4, 6, or 12 h). Mechanical properties were characterized using parallel plate rheometry, while fluorigenic properties were examined with a spectrofluorimetric plate reader and with a standard, inverted epifluorescent microscope. Additionally, Fourier transform infrared spectroscopy was used to characterize and track the crosslinking reaction in real-time. Genipin produced significant concentration- and incubation-dependent increases in the storage modulus, loss modulus, and fluorescence intensity. Storage modulus was strongly correlated to fluorescence exponentially. Minimal cytotoxicity was observed for exposure of L929 fibroblasts cultured within collagen gels to 1 mM genipin for 24 h, but significant cell death occurred for 5 and 10 mM genipin. We conclude that genipin can be used to stiffen collagen gels in a relatively short time frame, that low concentrations of genipin can be used to crosslink cell-populated collagen gels to affect cell behavior that is influenced by the mechanical properties of the tissue scaffold, and that the degree of crosslinking can be reliably assayed optically via simple fluorescence measurements.     

Effect of resin matrix ratio, storage medium, and time upon the physical properties of a radiopaque dental composite

Three light curing composite pastes with varying resin matrix ratios [bisphenol A-glycidyl methacrylate (BIS-GMA)/urethane tetramethacrylate (UTMA) 25:75, BIS-GMA/UTMA 50:50, and BIS-GMA/UTMA 75:25 w/w%] were prepared in combination with a radiopaque glass powder and camphorquinone photoinitiator. Cured samples were aged at 37 degrees C in three food simulating media such as citrate buffer (pH 4.0), PBS buffer (pH 7.4), and 75% ethyl alcohol. Samples were withdrawn at specific intervals of 1, 15, 30, 45, and 60 days and tested for changes in mechanical properties, sorption, and solubility characteristics. Statistical calculations revealed significant changes in compressive strength (CS) for composites depending on the resin matrix ratio and type of medium used for aging. While diametral tensile strength (DTS) was affected adversely in citrate medium for composites with higher urethane content, samples stored in alcohol medium showed deterioration of transverse strength (TS) and microhardness (VMH) for all composites studied. Increase in BIS-GMA content in the resin matrix and storage in alcohol medium resulted in higher sorption and solubility values and lower microhardness.     

A trial to prepare biodegradable collagen-hydroxyapatite composites for bone repair

This paper is a trial to prepare collagen-hydroxyapatite composites in vitro by an alternate immersion method. Collagen sponges of different biodegradabilities were prepared through chemical cross-linking of Type I collagen with glutaraldehyde (GA) at concentrations of 0.2, 1.0, and 2.0 wt%. The sponges were immersed at 37 degrees C in Tris-HCl-buffered solution containing 200 mM CaCl2 (pH 7.4) for 2 h and then in an aqueous solution of 120 mM Na2HPO4 (pH 9.3) for a 2 h further (one immersion cycle). The alternate immersion cycle was repeated for different times to obtain collagen-hydroxyapatite composites. The characterization of the resulting composites was performed by Fourier transform infrared spectroscopy (FT-IR). X-ray diffraction (XRD), and scanning electron microscopy (SEM). The weight of composites increased with an increase in immersion cycles and the rate of increase became greater with higher GA cross-linking levels for collagen sponge preparation. The pH of the phosphate solution decreased with the immersion cycle, which suggests H+ generation accompanied hydroxyapatite formation. Irrespective of the GA concentration and immersion cycle, every composite showed IR absorption bands attributable to phosphate and hydroxyl groups at 950-1100 or 550-650 and 3000-3500 cm(-1) and broad peaks specific to hydroxyapatite on the XRD charts. SEM study revealed small white clusters of hydroxyapatite interspersed uniformly on/in the collagen framework without any preferential orientation. The composite prepared from 0.2 wt% GA cross-linked collagen sponge which showed favourable characteristics was applied to a rat skull defect to evaluate its osteoconductivity as well as biodegradability. The formation of new bone tissue was histologically observed at the defect 12 weeks after application in marked contrast to the collagen sponge alone. The composite degraded without any inflammation reaction. It is concluded that the collagen-hydroxyapatite composite prepared by the present method is a biodegradable biomaterial of osteoconductivity applicable to bone repair.     

Cell-matrix interactions improve beta-cell survival and insulin secretion in three-dimensional culture

Controlled matrix interactions were presented to pancreatic beta-cells in three-dimensional culture within poly(ethylene glycol) hydrogels. Dispersed MIN6 beta-cells were encapsulated in gel environments containing the following entrapped extracellular matrix (ECM) proteins: collagen type I, collagen type IV, fibrinogen, fibronectin, laminin, and vitronectin. In ECM-containing gels, beta-cell survival was significantly better than in gels without ECM over 10 days. Correspondingly, apoptosis in encapsulated beta-cells was less in the presence of each matrix protein, suggesting the ability of individual matrix interactions to prevent matrix signaling-related apoptosis (anoikis). MIN6 beta-cells cultured in gels containing collagen type IV or laminin secreted more insulin in response to glucose stimulation than beta-cells in all other experimental conditions. Variations in collagen type IV or laminin concentration between 10 microg/mL and 250 microg/mL did not affect insulin secretion. Finally, beta-cell function in hydrogels presenting both collagen type IV and laminin revealed synergistic interactions. With a total protein concentration of 100 microg/mL, three gel compositions of varying ratios of collagen type IV to laminin (25:75, 50:50, and 75:25) were tested. In the presence of 25 microg/mL of collagen type IV and 75 microg/mL of laminin, beta-cell insulin secretion was greater than with laminin or collagen type IV individually. These results demonstrate that specific, rationally designed extracellular environments promote isolated beta-cell survival and function.     

软基质力学特性对滑膜间充质干细胞向软骨细胞分化的干预作用

背景：课题组前期研究表明,较软的培养基质对大鼠骨髓间充质干细胞的形态及细胞骨架有明显的影响。 目的：探讨不同弹性模量的聚丙烯酰胺凝胶软基质对人滑膜间充质干细胞向软骨细胞分化的影响。 方法：无菌条件下获取骨关节炎患者滑膜组织,有限稀释法获得原代人滑膜间充质干细胞,流式细胞术进行细胞表面标记物鉴定,多向诱导分化实验进行功能鉴定。用丙烯酰胺和甲叉双丙烯酰胺制备0.4,6,30 kPa 3个弹性模量的聚丙烯酰胺凝胶软基质作为培养人滑膜间充质干细胞的基底,在转化生长因子β1存在的情况下分别培养7 d和14 d,RT-PCR方法检测软骨形成相关基因COL2A1、CRTAC1 mRNA的表达,以6孔细胞培养板作为对照组。 结果与结论：在不同弹性模量上生长的人滑膜间充质干细胞表现出不同的细胞形态;软基质的弹性模量及培养时间对人滑膜间充质干细胞成软骨基因COL2A1、CRTAC1的表达有交互作用：7 d时,CRTAC1 mRNA在6 kPa弹性模量聚丙烯酰胺凝胶上表达量最高(F=44.350,P=0.000);7 d时,COL2A1 mRNA在0.4 kPa弹性模量聚丙烯酰胺软基质上的表达量最高(F=6.384,P=0.005)。较低弹性模量的聚丙烯酰胺凝胶软基质比常规细胞培养板更具有促进滑膜间充质干细胞向软骨细胞分化的作用。 中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程      

Hydroxyapatite nanoparticle loaded collagen fiber composites: microarchitecture and nanoindentation study

Hydroxyapatite (HA) nanoparticle-collagen composite materials with various HA/collagen weight ratios were prepared from HA/collagen dispersions using the solution deposition and electrospinning with static or rotating collectors. The composites with nanoparticle HA to collagen weight ratio of 80:20 can be easily prepared in the solution deposition approach, whereas in the electrospun fibrous composites it was possible to reach a maximum HA/collagen weight ratio of 30:70 while maintaining a good fibrous structure. The structure, surface morphology, and nanoindentation properties of these nanoparticle HA/collagen composites with different microarchitectures were investigated. The values from 0.2 GPa to 20 GPa for nanoindentation Young's modulus and from 25 MPa to 500 MPa for hardness, were obtained depending on the fabrication technique, composition, and microarchitecture of the composites. It was observed that the nanoindentation Young's modulus and hardness of the HA/collagen composite materials seem to achieve maximum values for 45-60% HA content by weight.     

Insolubilized properties of UV-irradiated CO3 apatite-collagen composites

To examine the response to biological hard tissues, a carbonate-containing hydroxyapatite with chemical composition and crystallinity similar to those of bone was synthesized at pH 7.4 and 60 degrees C. The apatite powder was mixed with collagen solution, whose antigenicity had been removed by enzymatic treatment, and formed into apatite-collagen pellets. After insolubilization by UV-irradiation for 4 h, the composites showed remarkably reduced disintegration and maintained their shape under 3.6 MPa of stress after 1 wk incubation in 0.9% NaCl solution. They showed good biocompatibility when implanted beneath the periosteum cranii of rats. The UV-irradiated sample kept its features well and was packed with newly created material 3 wk after implantation.     

A trial to prepare biodegradable collagen–hydroxyapatite composites for bone repair

This paper is a trial to prepare collagen-hydroxyapatite composites in vitro by an alternate immersion method. Collagen sponges of different biodegradabilities were prepared through chemical cross-linking of Type I collagen with glutaraldehyde (GA) at concentrations of 0.2, 1.0, and 2.0 wt%. The sponges were immersed at 37°C in Tris-HCl-buffered solution containing 200 mM CaCl₂ (pH 7.4) for 2 h and then in an aqueous solution of 120 mM Na₂HPO₄ (pH 9.3) for a 2 h further (one immersion cycle). The alternate immersion cycle was repeated for different times to obtain collagen-hydroxyapatite composites. The characterization of the resulting composites was performed by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). The weight of composites increased with an increase in immersion cycles and the rate of increase became greater with higher GA cross-linking levels for collagen sponge preparation. The pH of the phosphate solution decreased with the immersion cycle, which suggests H⁺ generation accompanied hydroxyapatite formation. Irrespective of the GA concentration and immersion cycle, every composite showed IR absorption bands attributable to phosphate and hydroxyl groups at 950-1100 or 550-650 and 3000-3500 cm^-1 and broad peaks specific to hydroxyapatite on the XRD charts. SEM study revealed small white clusters of hydroxyapatite interspersed uniformly on/in the collagen framework without any preferential orientation. The composite prepared from 0.2 wt% GA cross-linked collagen sponge which showed favourable characteristics was applied to a rat skull defect to evaluate its osteoconductivity as well as biodegradability. The formation of new bone tissue was histologically observed at the defect 12 weeks after application in marked contrast to the collagen sponge alone. The composite degraded without any inflammation reaction. It is concluded that the collagen-hydroxyapatite composite prepared by the present method is a biodegradable biomaterial of osteoconductivity applicable to bone repair.     

Young's modulus of collagen at slow displacement rates

Collagen is a key structural component of extracellular matrix and its mechanical properties, particularly its stiffness, have been shown to influence cell function. This study explores the mechanical behavior of type I collagen gels at low rates relevant to that of cell motion. The Young's modulus, E, was obtained for collagen samples of concentrations 1.3, 2 and 3 mg/ml at varying crosshead displacement rates: 0.01, 0.1 and 1 mm/min. Local strain measurement in the gage section were used for both the strain and strain rate determination. The power law models for the modulus at these low strain rates show that the values converge as the displacement rate approaches a quasistatic state. This study provides data that was unavailable in the past on the Young's modulus of collagen at rates relevant to the cell.     

Hydrolysis and release behavior of hydrolyzable poly(etherurethane) gels derived from saccharide-, L-lysine-derivatives,and poly(propylene glycol)

Four different poly(ether urethane) gels were prepared by polyaddition of saccharide derivatives ( 1 , 2 , 3α , or 3β ) and poly(propylene glycol) with an L -lysine-derived diisocyanate, methyl (S)-2,6-diisocyanatohexanoate ( 4 ). Dibutyltin dilaurate and triisocyanate 5 , that was also derived from L -lysine, were used as a catalyst and a crosslinking agent, respectively. Hydrogels containing 1 , 2 or 3α were hydrolyzed in phosphate buffers (pH 5.5, 7.0, 8.0) at 27°C, while the hydrolysis of the gel bearing 3β did not occur even after immersion for 3 months. Release of 5(6)-carboxyfluorescein (CF) and magnesium 8-anilino-1-naphthalenesulfonate (ANS) from the hydrogels was investigated in buffers of different pH. The release behavior was significantly controlled by the degree of hydrolysis of the gels. Both hydrolysis and the release behavior of these gels depended on the pH value.     

Degradation of collagen suture in vitro and in vivo.

In vitro and in vivo degradation of collagen suture was investigated focussing on the change in the mechanical properties and weight. The in vitro hydrolysis was carried out for catguts using collagenase (pH 7.4) and pepsin (pH 1.6), simulating the in vivo environments. The kinetic study on the weight loss of the fibre at the collagenase hydrolysis suggested that the degradation proceeded gradually from the surface of the fibre into the core. The enzymatic hydrolysis was different from the non-enzymatic acidic hydrolysis which resulted in almost homogeneous degradation throughout the cross-section of the fibre from the beginning of the hydrolysis reaction. The rate of weight loss with enzymatic hydrolysis was in good agreement with that predicted under the assumption of continuous erosion from the surface. When the collagen sutures were implanted in the subdermal tissue of rabbits, severe infiltration of macrophages and neutrophils was observed at 4 wk post-implantation, probably because of the degradation products from the implanted sutures. Comparison of the tensile strength decrease with the weight loss observed at the in vivo degradation revealed that enzymatic and non-enzymatic hydrolysis occurred concurrently in the subcutaneous tissue.     

Insolubilization of apatite-collagen composites by UV irradiation

The physico-chemical properties and biocompatibility of insolubilized apatite-collagen composites were examined. A carbonate-containing hydroxyapatite with chemical composition and crystallinity similar to that of bone was synthesized at pH 7.4 and 60 degrees C. The apatite powder was mixed with collagen solution, whose antigenicity had been removed by enzymatic treatment and formed into apatite-collagen pellets. After insolubilization by UV irradiation for 4 h, the composites showed remarkably reduced disintegration and showed good biocompatibility when implanted into rat abdomen.     

Preparation of a collagen/polymer hybrid gel designed for tissue membranes. Part I: Controlling the polymer–collagen cross-linking process using an ethanol/water co-solvent

The drawback with collagen/2-methacryloyloxyethyl phosphorylcholine (MPC) polymer hybrid gels (collagen/phospholipid polymer hybrid gels) prepared in alkaline morpholinoethane sulfonic acid (MES) aqueous solution is that the cross-linking rate between the polymer and the collagen is low. To solve this problem, ethanol has been adopted as the reaction solvent, to prevent 1-ethyl-3-(3-dimethylaminopropyl)-1-carbodiimide hydrochloride (EDC) hydrolysis. Alterations in the ethanol mole concentration changed the cross-linking rate between the MPC polymer and the collagen gel. Prevention of EDC hydrolysis is clearly observed; protonation of carboxyl groups implies that the ratio of ethanol to water should be controlled. The polymer shows signs of penetration into the collagen gel layer, thus forming a totally homogeneous phase gel. This affects the mechanical strength of the collagen gel, making the gel much stiffer and brittle with an increase in the swelling ratio, as compared with that prepared in MES buffer. However, it is possible to obtain a collagen/phospholipid polymer hybrid gel with a high polymer portion and the cross-linking rate can be successfully controlled.     

Effects of pH on human bone marrow stromal cells in vitro: implications for tissue engineering of bone

The objective of this study was to address the hypothesis that changes in extracellular pH alter collagen gene expression, collagen synthesis, and alkaline phosphatase activity in bone marrow stromal cells (BMSCs). Potential effects of pH on cell function are of particular importance for tissue engineering because considerable effort is being placed on engineering biodegradable polymers that may generate a local acidic microenvironment on degradation. Human and murine single-cell marrow suspensions were plated at a density of 2 x 10(4) cells/cm(2). After 7 days in culture, the pH of the culture medium was adjusted to one of six ranges: > or = 7.8, 7.5.-7.7, 7.2-7.4, 6.9-7.1, 6.6-6.8, or < or = 6.5. After 48 h of exposure to an altered pH, alkaline phosphatase activity and collagen synthesis decreased significantly with decreasing pH. This decrease was two-to threefold as pH decreased from 7.5 to 6.6. In contrast, alpha1(I) procollagen mRNA levels increased two- to threefold as pH was decreased. The trend in osteocalcin mRNA expression was opposite to that of collagen. Small shifts in extracellular pH led to significant changes in the ability of BMSCs to express markers of the osteoblast phenotype. These pH effects potentially relate to the microenvironment supplied by a tissue-engineering scaffold and suggest that degrading polymer scaffolds may influence the biologic activity of the cells in the immediate environment.     

Effects of neighboring sulfides and pH on ester hydrolysis in thiol-acrylate photopolymers

Networks synthesized through thiol-acrylate photopolymerization or Michael-type addition step growth reactions contain esters with neighboring sulfide groups. Previous work has demonstrated that these esters are readily hydrolyzable at physiological pH. Here, the influence of the distance between the sulfide and ester, as well as the water concentration, on ester hydrolysis was characterized. These preliminary results indicate that reducing the number of carbons between the sulfide and the ester from 2 to 1 increased the rate of ester hydrolysis from 0.022+/-0.001 to 0.08+/-0.015days(-1). Increases in ester hydrolysis rates were also observed as hydrophilicity increased for oligomers prepared from a trithiol, tetrathiol and dithiol monomer (0.012+/-0.003, 0.032+/-0.004, and 0.091+/-0.003days(-1), respectively). Additionally, in bulk-eroding polymeric biomaterials, variations in pH impacted the ester hydrolysis rate. This work confirms that small variations in buffer pH predictably alter the mass loss profile of a thiol-acrylate photopolymer. More specifically, as buffer pH was changed from 7.4 to 8.0, the rate of ester hydrolysis increased from 0.074+/-0.003 to 0.28+/-0.005days(-1). The magnitude of this observed change in ester hydrolysis rate was correlated to the increase in hydroxide ion concentration that accompanied this pH change.     

Polylactic acid-phosphate glass composite foams as scaffolds for bone tissue engineering

Phosphate glass (PG) of the composition 0.46(CaO)-0.04(Na(2)O)-0.5(P(2)O(5)) was used as filler in poly-L-lactic acid (PLA) foams developed as degradable scaffolds for bone tissue engineering. The effect of PG on PLA was assessed both in bulk and porous composite foams. Composites with various PG content (0, 5, 10, and 20 wt %) were melt-extruded, and either compression-molded or foamed through supercritical CO(2). Dynamic mechanical analysis on the bulk composites showed that incorporating 20 wt % PG resulted in a significant increase in storage modulus. Aging studies in deionized water in terms of weight loss, pH change, and ion release inferred that the degradation was due to PG dissolution, and dependent on the amount of glass in the composites. Foaming was only possible for composites containing 5 and 10 wt % PG, as an increase in PG increased the foam densities; however, the level of porosity was maintained above 75%. PLA-T(g) in the foams was higher than those obtained for the bulk. Compressive moduli showed no significant reinforcement with glass incorporation in either expansion direction, indicating no anisotropy. Biocompatibility showed that proliferation of human fetal bone cells was more rapid for PLA compared to PLA-PG foams. However, the proliferation rate of PLA-PG foams were similar to those obtained for foams of PLA with either hydroxyapatite or beta-tricalcium phosphate.