Poly(glycerol sebacate) (PGS) continues to attract attention for biomedical applications owing to its favorable combination of properties. Conventionally polymerized by a two‐step polycondensation of glycerol and sebacic acid, variations of synthesis parameters, reactant concentrations or by specific chemical modifications, PGS materials can be obtained exhibiting a wide range of physicochemical, mechanical, and morphological properties for a variety of applications. PGS has been extensively used in tissue engineering (TE) of cardiovascular, nerve, cartilage, bone and corneal tissues. Applications of PGS based materials in drug delivery systems and wound healing are also well documented. Research and development in the field of PGS continue to progress, involving mainly the synthesis of modified structures using copolymers, hybrid, and composite materials. Moreover, the production of self‐healing and electroactive materials has been introduced recently. After almost 20 years of research on PGS, previous publications have outlined its synthesis, modification, properties, and biomedical applications, however, a review paper covering the most recent developments in the field is lacking. The present review thus covers comprehensively literature of the last five years on PGS‐based biomaterials and devices focusing on advanced modifications of PGS for applications in medicine and highlighting notable advances of PGS based systems in TE and drug delivery.
Cardiac tissue engineering is a promising strategy to prevent functional deterioration or even to enhance cardiac function upon myocardial infarction. Here, electrospun fiber mats containing different combinations of electrically conductive polyaniline, collagen, and/or hyaluronic acid are assessed regarding material properties and compatibility with cardiomyocyte attachment and function. Microstructure analysis reveals that collagen fiber mats contain a wide range of fiber diameters after crosslinking (from ≈300 nm to ≈5 µm); all other fiber mats contain fibers in the range of ≈120 to ≈300 nm. Fiber mats exhibit comparable electrical conductivity to and greater mechanical properties than the native human myocardium, which is considered beneficial. Cell–matrix interaction analysis utilizing postnatal rat cardiomyocytes reveals that the fiber mats are non‐cytotoxic and permit cell attachment and contraction. Fiber mats containing collagen (9.89%), hyaluronic acid (1.1%), and polyaniline (PANi, 1.34%) exhibit the most favorable properties with longer contraction time, higher contractile amplitude, and lower beating rates. Improved contraction is accompanied by increased connexin 43 expression. Importantly, this fiber mat is a suitable material for human‐induced pluripotent stem cell–derived cardiomyocytes regarding cytotoxicity, cell attachment, and function. Collectively, these data demonstrate that fiber mats made of collagen, hyaluronic acid, and polyaniline are promising materials for cardiac tissue engineering.
Micrometer-scale biochemical or topographical patterning is commonly used to guide the cell attachment and growth, but the ability to combine these patterns into an integrated surface with defined chemical and geometrical characteristics still remains a technical challenge. Here, we present a technical solution for simultaneous construction of 3D morphologies, in the form of channels, on porous membranes along with precise transfer of extracellular matrix proteins into the channels to create patterns with geometrically restricting features. By combining the advantages of microthermoforming and microcontact printing, this technique offers a unique patterning process that provides spatiotemporal control over morphological and chemical feature in a single step. By use of our 3D-microcontact printing (3DμCP), determined microstructures like channels with different depths and widths even with more complex patterns can be fabricated. Collagen, fibronectin, and laminin were successfully transferred inside the predesigned geometries, and the validity of the process was confirmed by antibody staining. Cells cultivated on 3DμCP patterned polycarbonate membrane have shown selective adhesion and growth. This technique offers a novel tool for creating freeform combinatorial patterning on the thermoformable surface.
The vascular system represents the key supply chain for nutrients and oxygen inside the human body. Engineered solutions to produce sophisticated alternatives for autologous or artificial vascular implants to sustainably replace diseased vascular tissue still remain a key challenge in tissue engineering. In this paper, cell‐laden 3D bioplotted hydrogel vessel‐like constructs made from alginate di‐aldehyde (ADA) and gelatin (GEL) are presented. The aim is to increase the mechanical stability of fibroblast‐laden ADA‐GEL vessels, tailoring them for maturation under dynamic cell culture conditions. BaCl2 is investigated as a crosslinker for the oxidized alginate‐gelatin system. Normal human dermal fibroblast (NHDF)‐laden vessel constructs are optimized successfully in terms of higher stiffness by increasing ADA concentration and using BaCl2, with no toxic effects observed on NHDF. Contrarily, BaCl2 crosslinking of ADA‐GEL accelerates cell attachment, viability, and growth from 7d to 24h compared to CaCl2. Moreover, alignment of cells in the longitudinal direction of the hydrogel vessels when extruding the cell‐laden hydrogel crosslinked with Ba2+ is observed. It is possible to tune the stiffness of ADA‐GEL by utilizing Ba2+ as crosslinker. In addition, a customized, low‐cost 3D printed polycarbonate (PC) perfusion chamber for perfusion of vessel‐like constructs is introduced.
Electrospun fibers based on biodegradable polyanionic or polycationic biopolymers are highly beneficial for biomedical applications. In this work, electrospun nanofibers made from poly(epsilon caprolactone) (PCL), chitosan (CS) and κ-carrageenan (κ-C) were successfully fabricated using several mixtures of benign solvents containing formic acid (FA) and acetic acid (AA). The addition of κ-carrageenan improved the preparation procedure for the production of PCL/CS fibers by electrospinning. Moreover, a polymer mixture was selected to be stored at -20 °C for one month with the purpose to study the properties of the resulting fiber mat. The results indicated that fiber characteristics were not seriously compromised compared to the ones of those fabricated with the original solution, which represents an important reduction in produced waste. Thus, the interactions that occur between positively and negatively charged hydrophilic polysaccharides might induce higher stability to the linear aliphatic polyester in the polymer mixture. All fiber mats were morphologically, physico-chemically and mechanically characterized, showing average fiber diameters in the nano scale. A direct cell viability assay using ST-2 cells demonstrated cell proliferation after 7 days of incubation for all prepared fiber mats, confirming their suitability as potential candidates for bone tissue engineering and wound healing applications.
The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adem.202101768.
The major purpose of cardiac patches is to deliver healthy cells to infarcted tissues. Such cardiac patches must fulfill specific mechanical as well as chemical requirements. Herein, bi‐component cardiac patches are investigated with regard to their layer adhesion. Combinations of salt‐leached porous poly (glycerol sebacate) (PGS) films with a layer of electrospun‐gelatin fibers are produced. Gelatin fibers are fabricated by solution electrospinning using 20 wt% gelatin in 98 v% formic acid. Fibers are attached to PGS films either via direct electrospinning on top of the film or via combining as spun fiber mats with PGS using gelatin as glue. Scanning electron microscopy (SEM) images show that fiber mats adapt to the rough surface of the porous PGS film. In contrast, fibers spun directly onto films show poor adhesion and only a few fibers are attached to the PGS substrate. Fourier transform infrared (FTIR) analysis, contact‐angle measurements, and pull‐off adhesion tests of the bi‐component patches confirm these results. Modified pull‐off adhesion tests of the two layers show that combining as spun gelatin fiber mats with porous PGS substrates by gluing leads to excellent material adhesion before and after incubation for up to 14 days.
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