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Biobased and biodegradable films were prepared by physically mixing 2,3-dialdehyde cellulose (DAC) with two other biopolymers, zein and gelatin, in three different proportions. The antimicrobial activities of the composite blends against Gram-positive and Gram-negative bacteria increase with the increase of DAC content. Cell viability tests on mammalian cells showed that the materials were not cytotoxic. In addition, DAC and gelatin were able to promote thermal degradation of the blends. However, DAC increased the stiffness and decreased the glass transition temperature of the blends, while gelatin was able to decrease the stiffness of the film. Morphological analysis showed the effect of DAC on the surface smoothness of the blends. The contact angle confirmed that all blends were within the range of hydrophilic materials. Although all the blends showed impressive performance for wound dressing application, the blend with gelatin might be more suitable for this purpose due to its better mechanical performance and antibacterial activity.

The viscoelastic properties of polymer blends of poly(glycerol sebacate) (PGS) and poly(butylene succinate-dilinoleate) (PBS-DLA) copolymer intended for cardiac tissue patches are investigated by dynamic flat punch nanoindentation at frequencies ranging from 1 to 45 Hz. The storage modulus is found to depend weakly on the testing frequency, the lowest value being for 1 Hz, which corresponds to the usual heart rate. More significantly, it is found that varying the PGS content between 40 and 70 wt% allows tuning the storage modulus of the blends between 11 and 39 MPa. The reliability of the nanoindentation method is validated by reference dynamic mechanical measurements on thicker PBS-DLA samples using a tensile testing machine.

Nano- and micro-scale topographical features play a critical role in the induction and maintenance of various cellular properties and functions, including morphology, adhesion, gene regulation, and cell-to-cell communication. In addition, recent studies have indicated that the structure and function of heart tissue are also sensitive to mechanical cues at the nano- and micro-scale. Although fabrication methods exist for generating topographical features on polymeric scaffolds for cell culture, current techniques, especially those with nano-scale resolution, are typically complex, prohibitively expensive and not accessible to most biology laboratories. Here, we present a simple and tunable fabrication method for the production of patterned electrospun fibers that simulate the complex anisotropic and multi-scale architecture of cardiac tissue, to promote cardiac cell alignment. This method is based on the combination of electrospinning and soft lithography techniques, in which electrospun fibers, based on a blend of poly(glycerol sebacate) and poly(caprolactone), were collected on a patterned Teflon-coated silicon wafer with imprinted topographical features. Different surface topographies were investigated, such as squares and grooves, with constant or different interspatial distances. In vitro cell culture studies successfully demonstrated the alignment of both C2C12 myoblasts and neonatal rat cardiomyocytes on fabricated electrospun patterned surfaces. C2C12 cells were cultured over a period of 72 h to study the effect of topographical cues on cell morphology. Cells attached within the first 8 h after seeding and after 24 h most of the cells started to align responding to the topographical cues. Similarly, cardiomyocytes responded to the topographical features by aligning themselves and by expressing Connexin 43 along cellular junctions. Summarizing, we have developed a new method with the potential to significantly promote cardiac tissue engineering by fabricating electrospun fibers with defined topographical features to guide and instruct donor and/or host cells.

A novel self-crosslinked hydrogel with a delivery carrier was prepared by incorporating 0.5, 1, and 4% (w/v) oxidized alginate di-aldehyde microspheres (Ads) into a 5% (w/v) gelatin matrix. The Ads have a two-fold function. Namely, they act as delivery vehicles and promote the self-crosslinking of the hybrid hydrogel. Both light and scanning electron microscopy confirmed a homogenous distribution of the Ads in the gelatin matrix. In contrast to the unmodified alginate microspheres, clustering and sedimentation could be avoided. Furthermore, their incorporation improved the mechanical properties and the thermal stability of the thermosensitive gelatin. Crosslinking was completed after 213 min at 37 °C. The addition of 1% (w/w) borax shortened the crosslinking process to 59.5 min. The crosslinking time could be further reduced to 20 min by performing the Schiff base reaction at an elevated temperature of 45 °C.

The application of a cardiac patch made of biodegradable polymer is a novel approach in regenerative therapies for infarcted cardiac tissue and aims to deliver healthy and functional cells on a mechanically supporting matrix to the damaged area of the myocardium. In this study a novel type of tissue engineered cardiac construct based on poly(glycerol sebacate) (PGS) blended with the corn protein zein was developed. Bead free electrospun PGS–zein fibers were fabricated using acetic acid as a benign solvent. In vitro degradation studies in PBS revealed a physicochemically stable system over a 28 day period showing only a slight drop in pH after 28 days. The results indicate that the novel PGS–zein fibrous structures are attractive biomaterials which can be valuable for cardiac patch applications thus warranting their further investigation in vitro and in vivo.

The present article investigates the use of a novel electrospun fibrous blend of poly(glycerol sebacate) (PGS) and poly(butylene succinate-butylene dilinoleate) (PBS-DLA) as a candidate for cardiac tissue engineering. Random electrospun fibers with various PGS/PBS-DLA compositions (70/30, 60/40, 50/50, and 0/100) were fabricated. To examine the suitability of these fiber blends for heart patches, their morphology, as well as their physical, chemical, and mechanical properties were measured before examining their biocompatibility through cell adhesion. The fabricated fibers were bead-free and exhibited a relatively narrow diameter distribution. The addition of PBS-DLA to PGS resulted in an increase of the average fiber diameter, whereas increasing the amount of PBS-DLA decreased the hydrophilicity and the water uptake of the nanofibrous scaffolds to values that approached those of neat PBS-DLA nanofibers. Moreover, the addition of PBS-DLA significantly increased the elastic modulus. Initial toxicity studies with C2C12 myoblast cells up to 72 h confirmed nontoxic behavior of the blends. Immunofluorescence analyses and scanning electron microscopy analyses confirmed that C2C12 cells showed better cell attachment and proliferation on electrospun mats with higher PBS-DLA content. However, immunofluorescence analyses of the 3-day-old rat cardiomyocytes cultured for 2 and 5 days demonstrated better attachment on the 70/30 fibers containing well-aligned sarcomeres and expressing high amounts of connexin 43 in cellular junctions indicating efficient cell-to-cell communication. It can be concluded, therefore, that fibrous PGS/PBS-DLA scaffolds exhibit promising characteristics as a biomaterial for cardiac patch applications.

Cardiac tissue engineering constructs are a promising therapeutic treatment for myocardial infarction, which is one of the leading causes of death. In order to further advance the development and regeneration of engineered cardiac tissues using biomaterial platforms, it is important to have a complete overview of the effects that substrates have on cardiomyocyte (CM) morphology and function. This article summarizes recent studies that investigate the effect of mechanical cues on the CM differentiation, maturation, and growth. In these studies, CMs derived from embryos, neonates, and mesenchymal stem cells were seeded on different substrates of various elastic modulus. Measuring the contractile function by force production, work output, and calcium handling, it was seen that cell behavior on substrates was optimized when the substrate stiffness mimicked that of the native tissue. The contractile function reflected changes in the sarcomeric protein confirmation and organization that promoted the contractile...

Bacterial communities form biofilms on a wide range of surfaces by synthesizing a cohesive and protective extracellular matrix. The morphology, internal structure and mechanical stability of a biofilm are largely determined by its constituent polymers. In addition to mediating adhesion to surfaces, biofilms control the uptake of molecules and regulate the permeability of the matrix to gases and chemicals. Since biofilms can cause significant problems in both industrial and healthcare settings, there is great interest in developing strategies that either inhibit their formation or facilitate their elimination. However, although important in this context, the material properties of bacterial biofilms are poorly understood. In particular, little is known about how the different components of a biofilm matrix contribute to its various physical characteristics, or how these are modified in response to environmental cues. In this review, we present an overview of the molecular composition of different bacterial biofilms and describe techniques for the characterization of their viscoelastic properties. Finally, we summarize our current understanding of how the mechanical properties of bacterial biofilms are altered by different environmental challenges, and we discuss initial insights into the relationship between these responses and the composition of the matrix.

Novel Nanocomposite films containing TiO2 nanoparticles incorporated in blend matrices of biocompatible and bioresorbable polymers, namely poly(glycerol sebacate) (PGS) and poly(3-hydroxybutyrate) P(3HB), were developed. The samples were fabricated via a sequential step of solvent casting followed by cross-linking. PGS/P(3HB) blends (controls) were fabricated in two different ratios, i.e. 7∶1 and 8∶1. Varying amounts of TiO2 nanoparticles (1 and 2 vol.-%) were incorporated into the matrices. SEM studies revealed that the TiO2 particles were distributed both within the matrix and on the surface of the films thus imparting surface nanotopography and increasing the surface roughness. These microstructural features combined with the cumulative effect of blending of the two polymeric systems influenced the wettability, chemical and mechanical properties of the films. In vitro degradation of the fabricated matrices in PBS medium over a 30 day period confirmed that the composites undergo weight loss and ...

Summary Poly (glycerol sebacate) (PGS) and poly (butylene succinate-dilinoleate) (PBS-DLA) are biodegradable polymers with potential application in cardiac tissue engineering. In the present study novel blends comprising PGS prepolymer and PBS-DLA were prepared with varying compositions (70/30, 60/40, 50/50, 40/60, 30/70 and 0/100 in weight percentage). The physical, chemical, and mechanical properties of the PGS/PBS-DLA blends were measured and compared. By adding PBS-DLA to PGS the need for curing PGS prepolymer was eliminated, as the blended films are chemically stable. With increasing amount of PBS-DLA the hydrophobicity of the blend system increased reaching values close to that of neat PBS-DLA films. Furthermore, addition of PBS-DLA significantly affected the mechanical properties of the blends, i.e. the elastic modulus of the blends was enhanced with increasing PBS-DLA addition from 1.2 MPa to 54 MPa. At the same time, PBS-DLA addition led to decreased degradation rate of the films. Furthermore the PBS-DLA counteracted the acidity of the free carboxylic groups on the free end chains of the PGS prepolymer. In vitro cytocompatibility studies indicated high biocompatibility. Taken together the results confirm that the novel PGS/PBS-DLA matrices exhibit promising characteristics as a biomaterial for application in cardiac regeneration approaches.

In this study biomimetic poly(glycerol sebacate) PGS matrix was developed for cardiac patch application. The rationale was that such matrices would provide conducive environment for the seeded cells at the interphase with PGS. From the microstructural standpoint, PGS was fabricated into dense films and porous PGS scaffolds. From the biological aspect, biomimetic PGS membranes were developed via covalently binding peptides Tyr-Ile-Gly-Ser-Arg (YIGSR) and Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP), corresponding to the epitope sequences of laminin and fibronectin, respectively onto the surface. To improve and enhance homogenous binding of peptides onto the PGS surface, chemical modification of its surface was carried out. A sequential regime of alkaline hydrolysis with 0.01 M NaOH for 5 min and acidification with 0.01 M HCl for 25 s was optimal. More COOH chemical group was exposed without causing deleterious effect on the bulk properties of the polymer as revealed by the physicochemical analysis carried out. HPLC analysis, chemical imaging and ToF-SIMS were able to establish the successful homogenous functionalization of PGS membranes with the peptides. Finally, the developed biomimetic membranes supported the adhesion and growth of rat and human cardiac progenitor cells.

The influence of conventional sterilization methods such as gamma irradiation, ethylene oxide treatment and steam exposure on the physical properties of poly(glycerol sebacate) (PGS) was investigated. Scanning electron microscope (SEM) observations, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and Raman spectra demonstrated that the applied sterilization methods do not induce adverse surface modifications. The sterilized samples also maintained their thermal and mechanical properties post-sterilization. In addition, gamma sterilized PGS films did not induce any toxicity when films were in contact with murine fibroblast 3T3 cells. PGS is compatible for all the sterilization methods used in this study, which is of relevance for the wider application of PGS in medical devices.

A mortar hybrid material is presented in which biomineralization processes are stimulated by adding a biological component, i.e., bacterial biofilm, to standard mortar. A material is obtained that exhibits increased roughness on the microscale and the nanoscale. Accordingly, the hybrid mortar not only resists wetting but also suppresses the uptake of water by capillary forces.

Many bacteria form surface-attached communities known as biofilms. Due to the extreme resistance of these bacterial biofilms to antibiotics and mechanical stresses, biofilms are of growing interest not only in microbiology but also in medicine and industry. Previous studies have determined the extracellular polymeric substances present in the matrix of biofilms formed by Bacillus subtilis NCIB 3610. However, studies on the physical properties of biofilms formed by this strain are just emerging. In particular, quantitative data on the contributions of biofilm matrix biopolymers to these physical properties are lacking. Here, we quantitatively investigated three physical properties of B. subtilis NCIB 3610 biofilms: the surface roughness and stiffness and the bulk viscoelasticity of these biofilms. We show how specific biomolecules constituting the biofilm matrix formed by this strain contribute to those biofilm properties. In particular, we demonstrate that the surface roughness and surface elasticity of 1-day-old NCIB 3610 biofilms are strongly affected by the surface layer protein BslA. For a second strain, B. subtilis B-1, which forms biofilms containing mainly γ-polyglutamate, we found significantly different physical biofilm properties that are also differently affected by the commonly used antibacterial agent ethanol. We show that B-1 biofilms are protected from ethanol-induced changes in the biofilm's stiffness and that this protective effect can be transferred to NCIB 3610 biofilms by the sole addition of γ-polyglutamate to growing NCIB 3610 biofilms. Together, our results demonstrate the importance of specific biofilm matrix components for the distinct physical properties of B. subtilis biofilms.

Poly(glycerol sebacate) (PGS) is a biodegradable polymer increasingly used in a variety of biomedical applications. This polyester is prepared by polycondensation of glycerol and sebacic acid. PGS exhibits biocompatibility and biodegradability, both highly relevant properties in biomedical applications. PGS also involves cost effective production with the possibility of up scaling to industrial production. In addition, the mechanical properties and degradation kinetics of PGS can be tailored to match the requirements of intended applications by controlling curing time, curing temperature, reactants concentration and the degree of acrylation in acrylated PGS. Because of the flexible and elastomeric nature of PGS, its biomedical applications have mainly targeted soft tissue replacement and the engineering of soft tissues, such as cardiac muscle, blood, nerve, cartilage and retina. However, applications of PGS are being expanded to include drug delivery, tissue adhesive and hard tissue ( i.e. , bone) regeneration. The design and fabrication of PGS based devices for applications that mimic native physiological conditions are also being pursued. Novel designs range from accordion-like honeycomb structures for cardiac patches, gecko-like surfaces for tissue adhesives to PGS (nano) fibers for extra cellular matrix (ECM) like constructs; new design avenues are being investigated to meet the ever growing demand for replacement tissues and organs. In less than a decade PGS has become a material of great scrutiny and interest by the biomedical research community. In this review we consolidate the valuable existing knowledge in the fields of synthesis, properties and biomedical applications of PGS and PGS-related biomaterials and devices.

Scaffolds for cardiac patch application must meet stringent requirements such as biocompatibility, biodegradability, and facilitate vascularization in the engineered tissue. Here, a bioactive, biocompatible, and biodegradable electrospun scaffold of poly(glycerol sebacate)-poly(e-caprolactone) (PGS-PCL) is proposed as a potential scaffold for cardiac patch application. The fibers are smooth bead free with average diameter = 0.8 ± 0.3 μm, mean pore size = 2.2 ± 1.2 μm, porosity = 62 ± 4%, and permeability higher than that of control biological tissue. For the first time, bioactive PGS-PCL fibers functionalized with vascular endothelial growth factor (VEGF) are developed, the approach used being chemical modification of the PGS-PCL fibers followed by subsequent binding of VEGF via amide bonding. The approach results in uniform immobilization of VEGF on the fibers; the concentrations are 1.0 μg cm(-2) for the PGS-PCL (H) and 0.60 μg cm(-2) for the PGS-PCL (L) samples. The bioactive scaffold supports the attachment and growth of seeded myogenic and vasculogenic cell lines. In fact, rat aortic endothelial cells also display angiogenic features indicating potential for the formation of vascular tree in the scaffold. These results therefore demonstrate the prospects of VEGF-functionalized PGS-PCL fibrous scaffold as promising matrix for cardiac patch application.

Scaffolds for cardiac tissue engineering must be designed to achieve adequate degradation kinetics and mechanical properties. In this study, bulk modification of poly(glycerol sebacate) (PGS) with different concentrations of thermal proteins (TP) was investigated to tailor the degradation properties of PGS. TP are polyamino acids formed by heating a mixture of amino acids with minimal proportions of glutamic or aspartic acid. The degradation study of TP-PGS was performed in vitro in phosphate buffered saline (PBS) solution over a 21 day period. Results showed that the degradation rate of PGS increased with increasing content of TP. After 21 days in PBS, degradation weight loss values of 9.40% ± 0.07, 7.3% ± 0.8 and 6.0% ± 0.4 were determined for PGS-TP2g, PGS-TP-0.01g and PGS-control, respectively. The studies also showed that TP altered the mechanical properties and surface hydrophilicity of PGS.

Organic/hydroxyapatite (HA) hybrid composites are promising materials for orthopedic applications. Proteinoid/HA hybrid microsphere composite is an ideal material for bioresorbable and biocompatible three-dimensional scaffolds. Proteinoids are thermally condensed mixtures of amino acids, forming microspheres via self-assembly of proteinoid chains. Synthesis of an onion-type multilayer proteinoid/HA hybrid composite is achieved by thermally condensing a mixture of amino acids in the presence of commercially available HA. Proteinoid/HA microsphere composite of about 40 μm are achieved as a result of heterogeneous nucleation of HA on proteinoids chains. The formation mechanism is based on the interaction between calcium ions of HA and carboxyl side groups of proteinoid. The morphology was gleaned by scanning electron microscopy, and the organic and inorganic constituents were characterized by several analytical methods.

The development of biomaterials for cardiac tissue engineering (CTE) is challenging, primarily owing to the requirement of achieving a surface with favourable characteristics that enhances cell attachment and maturation. The biomaterial surface plays a crucial role as it forms the interface between the scaffold (or cardiac patch) and the cells. In the field of CTE, synthetic polymers (polyglycerol sebacate, polyethylene glycol, polyglycolic acid, poly-l-lactide, polyvinyl alcohol, polycaprolactone, polyurethanes and poly(N-isopropylacrylamide)) have been proven to exhibit suitable biodegradable and mechanical properties. Despite the fact that they show the required biocompatible behaviour, most synthetic polymers exhibit poor cell attachment capability. These synthetic polymers are mostly hydrophobic and lack cell recognition sites, limiting their application. Therefore, biofunctionalization of these biomaterials to enhance cell attachment and cell material interaction is being widely investigated. There are numerous approaches for functionalizing a material, which can be classified as mechanical, physical, chemical and biological. In this review, recent studies reported in the literature to functionalize scaffolds in the context of CTE, are discussed. Surface, morphological, chemical and biological modifications are introduced and the results of novel promising strategies and techniques are discussed.