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It is becoming increasingly apparent that the architecture and mechanical properties of scaffolds, particularly with respect to mimicking features of natural tissues, are important for tissue engineering applications. Acrylated poly(glycerol sebacate) (Acr-PGS) is a material that can be crosslinked upon exposure to ultraviolet light, leading to networks with tunable mechanical and degradation properties through simple changes during Acr-PGS synthesis. For example, the number of acrylate functional groups on the macromer dictates the concentration of crosslinks formed in the resulting network. Three macromers were synthesized that form networks that vary dramatically with respect to their tensile modulus (~30 kPa to 6.6 MPa) and degradation behavior (~20 to 100% mass loss at 12 weeks) based on the extent of acrylation (~1 to 24%). These macromers were processed into biodegradable fibrous scaffolds using electrospinning, with gelatin as a carrier polymer to facilitate fiber formation and cell adhesion. The resulting scaffolds were also diverse with respect to their mechanics (tensile modulus ranging from ~60 kPa to 1 MPa) and degradation (~45 to 70% mass loss by 12 weeks). Mesenchymal stem cell adhesion and proliferation on all fibrous scaffolds was indistinguishable from controls. The scaffolds showed similar diversity when implanted on the surface of hearts in a rat model of acute myocardial infarction and demonstrated a dependence on scaffold thickness and chemistry in the host response. In summary, these diverse scaffolds with tailorable chemical, structural, mechanical and degradation properties are potentially useful for the engineering of a wide range of soft tissues.

To develop biodegradable polymers with favorable physicochemical and biological properties, we have synthesized a series of poly(terephthalate-co-phosphate)s using a two-step polycondensation. The diol 1,4-bis(2-hydroxyethyl) terephthalate was first reacted with ethylphosphorodichloridate (EOP), and then chain-extended with terephthaloyl chloride (TC). Incorporation of phosphate into the poly(ethylene terephthalate) backbone rendered the co-polymers soluble in chloroform and biodegradable, lowered the Tg, decreased the crystallinity and increased the hydrophilicity. With an EOP/TC molar feed ratio of 80 : 20, the polymer exhibited good film-forming property, yielding at 86.6 ± 1.6% elongation with an elastic modulus of 13.76 ± 2.66 MPa. This polymer showed a favorable toxicity profile in vitro and good tissue biocompatibility in the muscular tissue of mice. In vitro the polymer lost 21% of mass in 21 days, but only 20% for up to 4 months in vivo. It showed no deterioration of properties after sterilization by γ -irradiation at 2.5 Mrad on solid CO2. Release of FITC-BSA from the microspheres was diffusion-controlled and exceeded 80% completion in two days. Release of the hydrophobic cyclosporine-A from microspheres was however much more sustained and near zero-ordered, discharging 60% in 70 days. A limited structure–property relationship has been established for this co-polymer series. The co-polymers became more hydrolytically labile as the phosphate component (EOP) was increased and the side chains were switched from the ethoxy to the methoxy structure. Converting the methoxy group to a sodium salt further increased the degradation rate significantly. The chain rigidity as reflected in the Tg values of the co-polymers decreased according to the following diol structure in the backbone: ethylene glycol > 2-methylpropylene diol > 2,2-dimethylpropylene diol. The wide range of physicochemical properties obtainable from this co-polymer series should help the design of degradable biomaterials for specific biomedical applications.

An injectable, biodegradable hydrogel composite of oligo(poly(ethylene glycol) fumarate) (OPF) and gelatin microparticles (MPs) has been investigated as a cell and growth factor carrier for cartilage tissue engineering applications. In this study, hydrogel composites with different swelling ratios were prepared by crosslinking OPF macromers with poly(ethylene glycol) (PEG) repeating units of varying molecular weights from 1,000 ~ 35,000. Rabbit marrow mesenchymal stem cells (MSCs) and MPs loaded with transforming growth factor-β1 (TGF-β1) were encapsulated in the hydrogel composites in order to examine the effect of the swelling ratio of the hydrogel composites on the chondrogenic differentiation of encapsulated rabbit marrow MSCs both in the presence and absence of TGF-β1. The swelling ratio of the hydrogel composites increased as the PEG molecular weight in the OPF macromers increased. Chondrocyte-specific genes were expressed at higher levels in groups containing TGF-β1-loaded MPs and varied with the swelling ratio of the hydrogel composites. OPF hydrogel composites with PEG repeating units of molecular weight 35,000 and 10,000 with TGF-β1-loaded MPs exhibited a 159 ± 95 and a 89 ± 31 fold increase in type II collagen gene expression at day 28, respectively, while OPF hydrogel composites with PEG repeating units of molecular weight 3,000 and 1,000 with TGF-β1-loaded MPs showed a 27 ± 10 and a 17 ± 7 fold increase in type II collagen gene expression, respectively, as compared to the composites with blank MPs at day 0. The results indicate that chondrogenic differentiation of encapsulated rabbit marrow MSCs within OPF hydrogel composites could be affected by their swelling ratio, thus suggesting the potential of OPF composite hydrogels as part of a novel strategy for controlling the differentiation of stem cells.

There is an increased interest in the development of bioactive polymeric dental composites and related materials that have potential for mineralized tissue regeneration and preservation. This study explores how the substitution of ethyl α-hydroxymethylacryate (EHMA) for 2-hydroxyethyl methacrylate (HEMA) in photo-activated 2,2-bis[p-(2'-hydroxy-3'-methacryloxypropoxy)phenyl]propane (Bis-GMA) and Bis-GMA/tri(ethylene glycol) dimethacrylate (TEGDMA) resins affected selected physicochemical properties of the polymers and their amorphous calcium phosphate (ACP) composites. Rate of polymerization and the degree of conversion (DC) of polymers {EHMA (E), HEMA (H), Bis-GMA/EHMA (BE), Bis-GMA/HEMA (BH), Bis-GMA/TEGDMA/EHMA (BTE) and Bis-GMA/TEGDMA/HEMA (BTH)} were assessed by photo-differential scanning calorimetry and Fourier-Transform Infrared (FTIR) spectroscopy. ACP/BTE and ACP/BTH composites were evaluated for DC, biaxial flexure strength (BFS), water sorption (WS) and mineral ion release. Mid-FTIR and near-IR measurements revealed the following order of decreasing DC: [E, H polymers (97.0 %)] > [BE copolymer (89.9 %)] > [BH copolymer (86.2 %)] > [BTE, BTH copolymers (85.5 %)] > [ACP/BTH composite (82.6 %)] > [ACP/BTE composite (79.3 %)]. Compared to HEMA, EHMA did not adversely affect the BFS of its copolymers and/or ACP composites. Lower WS of BTE copolymers and composites (28 % and 14 %, respectively, compared to the BTH copolymers and composites) only marginal reduced the ion release from ACP/BTE composites compared to ACP/BTH composites. More hydrophobic ACP composites with acceptable ion-releasing properties were developed by substituting the less hydrophilic EHMA for HEMA.

A novel self-crosslinkable and biodegradable macromer poly(caprolactone fumarate) (PCLF) has been developed for guided bone regeneration. This macromer is a copolymer of fumaryl chloride, which contains double bonds for in-situ crosslinking, and poly(ε-caprolactone) that has a flexible chain to facilitate self-crosslinkability. PCLF was characterized with Fourier transform infrared (FTIR) spectroscopy, 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, and gel permeation chromatography (GPC). Porous scaffolds were fabricated with sodium chloride particles as the porogen and a chemical initiation system. The PCLF scaffolds were characterized with scanning electron microscopy (SEM) and micro-computed tomography (micro-CT). The cytotoxicity and in vivo biocompatibility of PCLF were also assessed. Our results suggest that this novel copolymer, PCLF, is an injectable, self-crosslinkable, and biocompatible macromer that may be potentially used as a scaffold for tissue engineering applications.

A structural protein blend system based on silkworm silk fibroin and recombinant human tropoelastin is described. Silk fibroin, a semicrystalline fibrous protein with beta-sheet crystals provides mechanical strength and controllable biodegradation, while tropoelastin, a noncrystallizable elastic protein provides elasticity. Differential scanning calorimetry (DSC) and temperature modulated DSC (TMDSC) indicated that silk becomes miscible with tropoelastin at different blend ratios, without macrophase separation. Fourier transform infrared spectroscopy (FTIR) revealed secondary structural changes of the blend system (beta-sheet content) before and after methanol treatment. Atomic Force Microscopy (AFM) nano-indentation demonstrated that blending silk and tropoelastin at different ratios resulted in modification of mechanical features, with resilience from ~68% to ~97%, and elastic modulus between 2~9Mpa, depending on the ratio of the two polymers. Some of these values are close to those of native aortic elastin or elastin-like polypeptides. Significantly, during blending and drying silk-tropoelastin form micro- and nano-scale porous morphologies which promote human mesenchymal stem cell attachment and proliferation. These blends offer a new protein biomaterial system for cell support and tailored biomaterial properties to match mechanical needs.

Due to the biocompatibility of poly(ethylene glycol) (PEG), PEG-based hydrogels have attracted considerable interest for use as biomaterials in tissue engineering applications. In this work, we show that PEG-based hydrogels prepared by photopolymerization of PEG macromonomers functionalized with either acrylate or acrylamide end-groups generate networks with crosslink junctions of high functionality. Although the crosslink functionality is not well controlled, the resultant networks are sufficiently well ordered to generate a distinct correlation peak in the small angle x-ray scattering (SAXS) related to the distance between crosslink junctions within the PEG network. The crosslink spacing is a useful probe of the PEG chain conformation within the hydrogel and ranges from approximately 6 to 16 nm, dependent upon both the volume fraction of polymer and the molecular weight of the PEG macromonomers. The presence of a peak in the scattering of photopolymerized PEG networks is also correlated with an enhanced compressive modulus in comparison to PEG networks reported in the literature with much lower crosslink functionality that exhibit no scattering peak. This comparison demonstrates that the method used to link together PEG macromonomers has a critical impact on both the nanoscale structure and the macroscopic properties of the resultant hydrogel network.

Currently available synthetic biodegradable elastomers are primarily composed of crosslinked aliphatic polyesters, which suffer from deficiencies including (1) high crosslink densities, which results in exceedingly high stiffness, (2) rapid degradation upon implantation, or (3) limited chemical moieties for chemical modification. Herein, we have developed poly(1,3-diamino-2-hydroxypropane-co-polyol sebacate)s, a new class of synthetic, biodegradable elastomeric poly(ester amide)s composed of crosslinked networks based on an amino alcohol. These crosslinked networks feature tensile Young’s modulus on the order of 1 MPa and reversable elongations up to 92%. These polymers exhibit in vitro and in vivo biocompatibility. These polymers have projected degradation half-lives up to 20 months in vivo.

Targeted drug delivery requires novel biodegradable, specific binding systems with longer circulation time. The aim of this study was to prepare biotinylated poly(lactic acid) (PLA) nanoparticles (NPs) which can meet regular requirements as well conjugate more biotins in the polymer to provide better binding with streptavidin. A biotin-graft-PLA was synthesized based on previously published biodegradable poly(ethylene glycol) (PEG)-graft-PLA, with one polymer molecule containing three PEG molecules. Newly synthesized biotin-graft-PLA had three biotins per polymer molecule, higher than the previous biotinylated PLA (≤1 biotin per polymer molecule). A PEG with a much lower molecular weight (MW ~1900) than the previous biotinylated PLA (PEG MW ≥ 3800), and thus more biocompatible, was used which supplied good nonspecific protein-resistant property compatible to PEG-graft-PLA, suggesting its possible longer stay in the bloodstream. Biotin-graft-PLA specifically bound to streptavidin and self-assembled into NPs, during which naproxen, a model small molecule (MW 230 Da) and hydrophobic drug, was encapsulated (encapsulation efficiency 51.88%). The naproxen-loaded NPs with particle size and zeta potential of 175 nm and −27.35 mV realized controlled release within 170 hours, comparable to previous studies. The biotin-graft-PLA NPs adhered approximately two-fold more on streptavidin film and on biotin film via a streptavidin arm both in static and dynamic conditions compared with PEG-graft-PLA NPs, the proven nonspecific protein-resistant NPs. The specific binding of biotin-graft-PLA NPs with streptavidin and with biotin using streptavidin arm, as well as its entrapment and controlled release for naproxen, suggest potential applications in targeted drug delivery.

Synthetic hydrogels based on poly(ethylene glycol) (PEG) have been used as biomaterials for cell biology and tissue engineering investigations. Bioactive PEG-based gels have largely relied on heterobifunctional or multi-arm PEG precursors that can be difficult to synthesize and characterize or expensive to obtain. Here, we report an alternative strategy, which instead uses inexpensive and readily available PEG precursors to simplify reactant sourcing. This new approach provides a robust system in which to probe cellular interactions with the microenvironment. We used the step-growth polymerization of PEG diacrylate (PEGDA, 3400 Da) with bis-cysteine matrix metalloproteinase (MMP)-sensitive peptides via Michael-type addition to form biodegradable photoactive macromers of the form acrylate-PEG-(peptide-PEG)m-acrylate. The molecular weight (MW) of these macromers is controlled by the stoichiometry of the reaction, with a high proportion of resultant macromer species greater than 500 kDa. In addition, the polydispersity of these materials was nearly identical for three different MMP-sensitive peptide sequences subjected to the same reaction conditions. When photopolymerized into hydrogels, these high MW materials exhibit increased swelling and sensitivity to collagenase-mediated degradation as compared to previously published PEG hydrogel systems. Cell-adhesive acrylate-PEG-CGRGDS was synthesized similarly and its immobilization and stability in solid hydrogels was characterized with a modified Lowry assay. To illustrate the functional utility of this approach in a biological setting, we applied this system to develop materials that promote angiogenesis in an ex vivo aortic arch explant assay. We demonstrate the formation and invasion of new sprouts mediated by endothelial cells into the hydrogels from embedded embryonic chick aortic arches. Furthermore, we show that this capillary sprouting and three-dimensional migration of endothelial cells can be tuned by engineering the MMP-susceptibility of the hydrogels and the presence of functional immobilized adhesive ligands (CGRGDS vs. CGRGES peptide). The facile chemistry described and significant cellular responses observed suggest the usefulness of these materials in a variety of in vitro and ex vivo biologic investigations, and may aid in the design or refinement of material systems for a range of tissue engineering approaches.

Two types of 32 arm star polymers incorporating amphiphilic block copolymer arms have been synthesized and characterized. The first type, stPCL-PEG32, is composed of a polyamidoamine (PAMAM) dendrimer as the core with radiating arms having poly(ε-caprolactone) (PCL) as an inner lipophilic block in the arm and poly(ethylene glycol) (PEG) as an outer hydrophilic block. The second type, stPLA-PEG32, is similar but with poly(l-lactide) (PLA) as the inner lipophilic block. Characterization with SEC, 1H NMR, FTIR, and DSC confirmed the structure of the polymers. Micelle formation by both star copolymers was studied by fluorescence spectroscopy. The stPCL-PEG32 polymer exhibited unimolecular micelle behavior. It was capable of solubilizing hydrophobic molecules, such as pyrene, in aqueous solution, while not displaying a critical micelle concentration. In contrast, the association behavior of stPLA-PEG32 in aqueous solution was characterized by an apparent critical micelle concentration of ca. 0.01 mg/mL. The hydrophobic anticancer drug etoposide can be encapsulated in the micelles formed from both polymers. Overall, the stPCL-PEG32 polymer exhibited a higher etoposide loading capacity (up to 7.8 w/w % versus 4.3 w/w % for stPLA-PEG32) as well as facile release kinetics and is more suitable as a potential drug delivery carrier.

There is a strong need for tissue engineering scaffolds that are mechanically robust, exhibit good biocompatibility, and can be made from readily available materials. To this end, blends of commercially available poly(ethylene glycol) diacrylate (PEGDA) with molecular weights of 400 and 3400 were UV-crosslinked at total polymer concentrations that varied systematically from 20 to 40 wt %. The compressive strength and cell viability were determined for each PEGDA mixture. The compressive modulus of the blends was maximized when the wt % ratio PEGDA3400/400 was about 40/60, with the compressive strength reaching 1.7 MPa. Cell viability results with a LIVE/DEAD fluorescence assay show an average viability of ~ 80% at a total PEGDA concentration of 20 wt %, for all blends. Increasing the total polymer concentration increased the compressive modulus of a polymer, but adversely affected cell viability for all the PEGDA blend compositions. The blend composition affected the mechanical behavior of the discs, where a higher degree of crosslinking was achieved by increasing the concentration of shorter chained PEGDA400, whereas elasticity was gained by incorporating longer chained PEGDA3400 into the blends. These results can be exploited for use in tissue engineering applications, where a mechanically robust scaffold is advantageous.

Hydrogels that degrade at different rates were prepared by copolymerizing slowly degrading macromer poly(ethylene glycol) (PEG) dimethacrylate with a faster degrading macromer poly(lactic acid)-b-PEG-b-poly(lactic acid) dimethacrylate. A clinically relevant population of neural cells composed of differentiated neurons and multipotent precursor cells was cultured within hydrogels. Within 2 h after encapsulation, metabolic activity was higher in hydrogels prepared with increasing levels of degradable content. This improvement was accompanied by a reduction in intracellular redox state and an increase in the fraction of glutathione in the reduced state, both of which persisted throughout 7 days of culture and which may be the result of radical scavenging by lactic acid. Importantly, an increase in cellular proliferation was observed in gels prepared with increasing degradable macromer content after 7 days of growth without a shift in the cellular composition of the culture toward the glial cell phenotype. The findings of this study provide additional insight into the growth of neural cells in PEG-based hydrogels. Results suggest that lactic acid released during gel degradation may impact the function of encapsulated cells, a finding of general interest to biomaterials scientists who focus on the development of degradable polymers for cell culture and drug delivery devices.

Shape-memory polymers are a class of smart materials that have recently been used in intelligent biomedical devices and industrial applications for their ability to change shape under a predetermined stimulus. In this study, photopolymerized thermoset shape-memory networks with tailored thermomechanics are evaluated to link polymer structure to recovery behavior. Methyl methacrylate (MMA) and poly(ethylene glycol) dimethacrylate (PEGDMA) are copolymerized to create networks with independently adjusted glass transition temperatures (Tg) and rubbery modulus values ranging from 56 to 92 °C and 9.3 to 23.0 MPa, respectively. Free-strain recovery under isothermal and transient temperature conditions is highly influenced by the Tg of the networks, while the rubbery moduli of the networks has a negligible effect on this response. The magnitude of stress generation of fixed-strain recovery correlates with network rubbery moduli, while fixed-strain recovery under isothermal conditions shows a complex evolution for varying Tg. The results are intended to help aid in future shape-memory device design and the MMA-co-PEGDMA network is presented as a possible high strength shape-memory biomaterial.

This study explores how substituting a new high molecular mass oligomeric poly(ethylene glycol) extended urethane dimethacrylate (PEG-U) for 2-hydroxyethyl methacrylate (HEMA) in photo-activated urethane dimethacrylate (UDMA) resins affects degree of vinyl conversion (DC), polymerization shrinkage (PS), stress development (PSSD) and biaxial flexure strength (BFS) of their amorphous calcium phosphate (ACP) composites. The composites were prepared from four types of resins (UDMA, PEG-U, UDMA/HEMA and UDMA/PEG-U) and zirconia-hybridized ACP. Introducing PEG-U improved DC while not adversely affecting PS, PSSD and the BFS of composites. This improvement in DC is attributed to the long, more flexible structure between the vinyl groups of PEG-U and its higher molecular mass compared to poly(HEMA). The results imply that PEG-U has the potential to serve as an alternative to HEMA in dental and other biomedical applications.

The purpose of this study was to develop poly(d,1-lactic-coglycolic acid) (PLGA)-based anastrozole microparticles for treatment of breast cancer. An emulsion/extraction method was used to prepare anastrozole sustained-release PLGA-based biodegradable microspheres. Gas chromatography with mass spectroscopy detection was used for the quantitation of the drug throughout the studies. Microparticles were formulated and characterized in terms of encapsulation efficiency, particle size distribution, surface morphology, and drug release profile. Preparative variables such as concentrations of stabilizer, drug-polymer ratio polymer viscosity, stirring rate, and ratio of internal to external phases were found to be important factors for the preparation of anastrozole-loaded PLGA microparticles. Fourier transform infrared with attenuated total reflectance (FTIR-ATR) analysis and differential scanning calorimetry (DSC) were employed to determine any interactions between drug and polymer. An attempt was made to fit the data to various dissolution kinetics models for multiparticulate systems, including the zero order, first order, square root of time kinetics, and biphasic models. The FTIR-ATR studies revealed no chemical interaction between the drug and the polymer. DSC results indicated that the anastrozole trapped in the microspheres existed in an amorphous or disordered-crystalline status in the polymer matrix. The highest correlation coefficients were obtained for the Higuchi model, suggesting a diffusion mechanism for the drug release. The results demonstrated that anastrozole microparticles with PLGA could be an alternative delivery method for the long-term treatment of breast cancer.

Injectable reverse thermal gels have great potentials as biomaterials for tissue engineering and drug delivery. However, most existing gels lack functional groups that can be modified with biomolecules that can guide cell/material interactions. We created an amine-functionalized ABA block copolymer, poly(ethylene glycol)-poly(serinol hexamethylene urethane), or ESHU. This reverse thermal gel consists of a hydrophobic block (B): poly(serinol hexamethylene urethane) and a hydrophilic block (A): poly(ethylene glycol). The polymer was characterized by GPC, FTIR and 1H FTNMR. Rheological study demonstrated that ESHU solution in phosphate-buffered saline initiated phase transition at 32°C and reached maximum elastic modulus at 37°C. The in vitro degradation tests performed in PBS and cholesterol esterase solutions revealed that the polymer was hydrolyzable and the presence of cholesterol esterase greatly accelerated the hydrolysis. The in vitro cytotoxicity tests carried out using baboon smooth muscle cells demonstrated that ESHU had good cytocompatibility with cell viability indistinguishable from tissue culture treated polystyrene. Subcutaneous implantation in rats revealed well tolerated accurate inflammatory response with moderate ED-1 positive macrophages in the early stages, which largely resolved 4 weeks post-implantation. We functionalized ESHU with a hexapeptide, Ile-Lys-Val-Ala-Val-Ser (IKVAVS), which gelled rapidly at body temperature. We expect this new platform of functionalizable reverse thermal gels to provide versatile biomaterials in tissue engineering and regenerative medicine.

The copolymerization of poly(3-hydroxybutyrate) (PHB) is a promising trend in bioengineering to improve biomedical properties, e.g. biocompatibility, of this biodegradable polymer. We used strain Azotobacter chroococcum 7B, an effective producer of PHB, for biosynthesis of not only homopolymer and its main copolymer, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB-HV), but also novel terpolymer, poly(3-hydroxybutyrate-co-3-hydroxyvalerate)-poly(ethylene glycol) (PHB-HV-PEG), using sucrose as the primary carbon source and valeric acid and poly(ethylene glycol) 300 (PEG 300) as additional carbon sources. The chemical structure of PHB-HV-PEG was confirmed by 1H nuclear-magnetic resonance analysis. The physico-chemical properties (molecular weight, crystallinity, hydrophilicity, surface energy) of produced biopolymer, the protein adsorption to the terpolymer, and cell growth on biopolymer films were studied. Despite of low EG-monomers content in bacterial-origin PHB-HV-PEG polymer, the terpolymer demonstrated significant improvement in biocompatibility in vitro in contrast to PHB and PHB-HV polymers, which may be coupled with increased protein adsorption, hydrophilicity and surface roughness of PEG-containing copolymer.

The principal aim of this study was to synthesize and characterize pH-sensitive biodegradable triblock copolymers containing a hydrophobic polyacetal segment for controlled drug delivery. Poly(ethylene glycol)-poly(ethyl glyoxylate)-poly(ethylene glycol) (PEG-PEtG-PEG) triblock copolymers with PEG molecular weights 500 (PEtG-PEG500) and 750 (PEtG-PEG750) were synthesized by PEtG end-capping with methoxy PEG via a carbamate linkage. Synthesized amphiphilic PEG-PEtG-PEG was characterized by 1H-NMR spectroscopy. Molecular weights of PEtG-PEG500 and PEtG-PEG750 were determined to be 2,823 and 3,387, respectively, by gel permeation chromatography. The polymers with a biodegradable polyacetal block underwent pH-dependent degradation via an acid-catalyzed hydrolysis. Paclitaxel (PTX)-loaded polymeric micelles were prepared by a dialysis method and the amount of PTX incorporated into the polymeric micelle formulations was 45,000 times greater than the water solubility of PTX at room temperature. The polymeric micelles prepared from the amphiphilic PEG-PEtG-PEG triblock copolymers have released the loaded PTX in a pH-dependent manner. The novel PEtG-based amphiphilic block copolymers can find applications for targeted and controlled drug delivery to the acidic environments found in tumors and intracellular compartments.

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 as well. 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.

We demonstrate spatial control over cell attachment on biodegradable surfaces by flowing cell adhesive poly (D-lysine) (PDL) in a trifluoroethanol (TFE)–water mixture through microfluidic channels placed on a biodegradable poly (lactic acid)–poly (ethylene glycol) (PLA–PEG) substrate. The partial solvent mixture swells the PLA–PEG within the confines of the microfluidic channels allowing PDL to diffuse on to the surface gel layer. When excess water is flowed through the channels substituting the TFE–water mixture, the swollen PLA surface collapses, entrapping PDL polymer. Results using preosteoblast human palatal mesenchymal cells (HEPM) indicate that this new procedure can be used for facile attachment of cells in localized regions. The PEG component of the PLA–PEG copolymer prevents cells from binding to the nonpatterned regions.

Low cytotoxicity and high gene transfection efficiency are critical issues in designing current non-viral gene delivery vectors. The purpose of the present work was to synthesize the novel biodegradable poly (lactic acid)-poly(ethylene glycol)-poly(l-lysine) (PLA-PEG-PLL) copolymer, and explore its applicability and feasibility as a non-viral vector for gene transport. PLA-PEG-PLL was obtained by the ring-opening polymerization of Lys(Z)-NCA onto amine-terminated NH2-PEG-PLA, then acidolysis to remove benzyloxycarbonyl. The tri-block copolymer PLA-PEG-PLL combined the characters of cationic polymer PLL, PLA and PEG: the self-assembled nanoparticles (NPs) possessed a PEG loop structure to increase the stability, hydrophobic PLA segments as the core, and the primary ɛ-amine groups of lysine in PLL to electrostatically interact with negatively charged phosphate groups of DNA to deposit with the PLA core. The physicochemical properties (morphology, particle size and surface charge) and the biological properties (protection from nuclease degradation, plasma stability, in vitro cytotoxicity, and in vitro transfection ability in HeLa and HepG2 cells) of the gene-loaded PLA-PEG-PLL nanoparticles (PLA-PEG-PLL NPs) were evaluated, respectively. Agarose gel electrophoresis assay confirmed that the PLA-PEG-PLL NPs could condense DNA thoroughly and protect DNA from nuclease degradation. Initial experiments showed that PLA-PEG-PLL NPs/DNA complexes exhibited almost no toxicity and higher gene expression (up to 21.64% in HepG2 cells and 31.63% in HeLa cells) than PEI/DNA complexes (14.01% and 24.22%). These results revealed that the biodegradable tri-block copolymer PLA-PEG-PLL might be a very attractive candidate as a non-viral vector and might alleviate the drawbacks of the conventional cationic vectors/DNA complexes for gene delivery in vivo.

Successful tissue regeneration requires that biomaterials have optimal bioactivity and mechanical properties. Heparin-containing hydrogels that can be crosslinked in situ were designed to contain tunable amounts of biological components (e.g. heparin, arginine–glycine–aspartate (RGD)) as well as to exhibit controlled mechanical properties (e.g. shear modulus). These gel parameters can also be tuned to provide controlled delivery of proteins, such as growth factors, for regulating cellular behavior. Maleimide-functionalized low-molecular-weight heparin (LWMH) was conjugated to a poly(ethylene glycol) (PEG) hydrogel. The elastic shear modulus, as assessed via oscillatory rheology experiments, could be tuned by the concentration of polymer in the hydrogel, and by the end group functionality of PEG. Hydrogels of two different moduli (2.8 and 0.4 kPa) were used to study differences in the response of human aortic adventitial fibroblasts (AoAF) in two-dimensional cell culture experiments. These experiments indicated that the AoAFs show improved adhesion to materials with the higher modulus. Evaluation of cell responses to hydrogels with RGD linked to the hydrogels via conjugation to PEG or to LMWH indicated improved cellular responses to these materials when the bioactive ligands were chemically attached through linkage to the PEG rather than to the LMWH. These results highlight important design considerations in the tailoring of these materials for cardiovascular tissue engineering applications.

There is a great need for biodegradable polymer scaffolds that can regulate the delivery of bioactive factors such as drugs, plasmids and proteins. Coaxial electrospinning is a novel technique that is currently being explored to create such polymer scaffolds by embedding within them aqueous based biological molecules. In this study we evaluated the influence of various processing parameters such as sheath polymer concentration, core polymer concentration and molecular weight, and salt ions within the core polymer on coaxial fiber morphology. The sheath polymer used in this study was poly(ε-caprolactone) (PCL) and the core polymer was poly(ethylene glycol) (PEG). We examined the effects of the various processing parameters on core diameters, total fiber diameters and sheath thicknesses of coaxial microfibers using a 24 full factorial statistical model. The maximum increase in total fiber diameter was observed with increase in sheath polymer (PCL) concentration from 9 to 11 wt % (0.49 ± 0.03 μm) and salt concentration within the core from 0 to 500 mM (0.38 ± 0.03 μm). The core fiber diameter was most influenced by the sheath and core polymers (PCL and PEG, respectively) concentrations, the latter of which increased from 200 to 400 mg/ml (0.40 ± 0.01 μm and 0.36 ± 0.01 μm, respectively). The core polymer (PEG) concentration had a maximal negative effect on sheath thickness (0.40 ± 0.03 μm), while salt concentration had the maximal positive effect (0.28 ± 0.03 μm). Molecular weight increases in core polymer (PEG) from 1.0 kDa to 4.6 kDa caused moderate increases in total and sheath fiber diameters and sheath thicknesses. These experiments provide important information that lays the foundation required for the synthesis of coaxial fibers with tunable dimensions.

There is a great need for biodegradable polymer scaffolds that can regulate the delivery of bioactive factors such as drugs, plasmids, and proteins. Coaxial electrospinning is a novel technique that is currently being explored to create such polymer scaffolds by embedding within them aqueous-based biological molecules. In this study, we evaluated the influence of various processing parameters such as sheath polymer concentration, core polymer concentration and molecular weight, and salt ions within the core polymer on coaxial fiber morphology. The sheath polymer used in this study was poly(ɛ-caprolactone) (PCL), and the core polymer was poly(ethylene glycol) (PEG). We examined the effects of the various processing parameters on core diameters, total fiber diameters, and sheath thicknesses of coaxial microfibers using a 24 full factorial statistical model. The maximum increase in total fiber diameter was observed with increase in sheath polymer (PCL) concentration from 9 to 11 wt% (0.49 ± 0.03 μm) and salt concentration within the core from 0 to 500 mM (0.38 ± 0.03 μm). The core fiber diameter was most influenced by the sheath and core polymer (PCL and PEG, respectively) concentrations, the latter of which increased from 200 to 400 mg/mL (0.40 ± 0.01 μm and 0.36 ± 0.01 μm, respectively). The core polymer (PEG) concentration had a maximal negative effect on sheath thickness (0.40 ± 0.03 μm), while salt concentration had the maximal positive effect (0.28 ± 0.03 μm). Molecular weight increases in core polymer (PEG) from 1.0 to 4.6 kDa caused moderate increases in total and sheath fiber diameters and sheath thicknesses. These experiments provide important information that lays the foundation required for the synthesis of coaxial fibers with tunable dimensions.