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In the process of generating organoids, basement membrane extracts or Matrigel are often used to encapsulate cells but they are poorly defined and contribute to reproducibility issues. While defined hydrogels are increasingly used for organoid culture, the effects of replacing Matrigel with a defined hydrogel on neural progenitor growth, neural differentiation, and maturation within organoids are not well-explored. In this study, the use of alginate hydrogels as a Matrigel substitute in spinal cord organoid generation is explored. It is found that alginate encapsulation reduces organoid size variability by preventing organoid aggregation. Importantly, alginate supports neurogenesis and gliogenesis of the spinal cord organoids at a similar efficiency to Matrigel, with mature myelinated neurons observed by day 120. Furthermore, using alginate leads to lower expression of non-spinal markers such as FOXA2, suggesting better control over neural fate specification. To demonstrate the feasibility of using alginate-based organoid cultures as disease models, an isogenic pair of induced pluripotent stem cells discordant for the ALS-causing mutation TDP43

Injectable hydrogels have gained considerable attention, but they are typically mechanically weak and subject to repeated physiological stresses in the body. Herein, we prepared polyurethane diacrylate (EPC-DA) hydrogels, which are injectable and can be photocrosslinked into fatigue-resistant implants. The mechanical properties can be tuned by changing photocrosslinking conditions, and the hybrid-crosslinked EPC-DA hydrogels exhibited high stability and sustained release properties. In contrast to common injectable hydrogels, EPC-DA hydrogels exhibited excellent antifatigue properties with90% recovery during cyclic compression tests and showed shape stability after application of force and immersion in an aqueous buffer for 35 days. The EPC-DA hydrogel formed a shape-stable hydrogel depot in an

Supramolecular hydrogels have attracted considerable interest due to their unique stimuli-responsive and self-healing properties. However, these hydrogel systems are usually achieved by covalent grafting of supramolecular units onto the polymer backbone, which in turn limits their reprocessability. Herein, we prepared a supramolecular hydrogel system by forming dynamic covalent crosslinks between 4-carboxyphenylboronic acid (CPBA) and polyvinyl alcohol (PVA). The system was then further crosslinked with either calcium ions or branched polyethylenimine (PEI) to generate hydrogels with distinctly different properties. Incorporation of calcium ions resulted in the formation of hydrogels with higher storage modulus of 7290 Pa but without self-healing properties. On the other hand, PEI-crosslinked hydrogel (PVA-CPBA-PEI) exhibited2000% critical strain value, demonstrated high stability over 52 days and showed sustained antibacterial effect. A combination of supramolecular interactions and dynamic covalent crosslinks can be an alternate strategy to fabricate next-generation hydrogel materials.

Hydrogels with more than one mode of crosslinking have gained interest due to improved control over hydrogel properties such as mechanical strength using multiple stimuli. In this work, sodium alginate was covalently conjugated onto thermoresponsive polyurethanes to prepare hybrid polymers (EPC-Alg) that are responsive to both temperature and Ca

Drug-delivery systems in cardiovascular applications regularly include the use of drug-eluting stents and drug-coated balloons to ensure sufficient drug transfer and efficacy in the treatment of cardiovascular diseases. In addition to the delivery of antiproliferative drugs, the use of growth factors, genetic materials, hormones and signaling molecules has led to the development of different nanoencapsulation techniques for targeted drug delivery. The review will cover drug delivery and coating mechanisms in current drug-eluting stents and drug-coated balloons, novel innovations in drug-eluting stent technologies and drug encapsulation in nanocarriers for delivery in vascular diseases. Newer technologies and advances in nanoencapsulation techniques, such as the use of liposomes, nanogels and layer-by-layer coating to deliver therapeutics in the cardiovascular space, will be highlighted.

Hydrogels are a promising drug delivery system for biomedical applications due to their biocompatibility and similarity to native tissue. Programming the release rate from hydrogels is critical to ensure release of desired dosage over specified durations, particularly with the advent of more complicated medical regimens such as combinatorial drug therapy. While it is known how hydrogel structure affects release, the parameters that can be explicitly controlled to modulate release ab initio could be useful for hydrogel design. In this review, we first survey common physical models of hydrogel release. We then extensively go through the various input parameters that we can exercise direct control over, at the levels of synthesis, formulation, fabrication and environment. We also illustrate some examples where hydrogels can be programmed with the input parameters for temporally and spatially defined release. Finally, we discuss the exciting potential and challenges for programming release, and potential implications with the advent of machine learning.

Modern implantable medical devices have evolved beyond serving as physical surrogates, to also playing an active role in restoring bodily functions. The progress of implantable medical devices is the culmination of advances in various scientific fields such as material science, microelectronics and biomaterials. The use of polymers in biomedical applications is highly attractive, especially in soft tissue applications as polymers have the potential to elicit appropriate host tissue response. However, homopolymers often do not encompass all the desired characteristics such as mechanical properties, degradability, biocompatibility or bio-functionality. The concepts of polymer blending or polymer composites were introduced to overcome the inadequacies when using a single polymer in cardiovascular applications. Through polymer blending, polymer scaffolds made up of two or more polymers can yield scaffold stiffness closer to the human myocardium and improved hydrophilicity for better cell interaction and improved biodegradability. Polymer composites, which utilizes to reinforce the base polymer, have demonstrated improved the compliance of the vascular graft similar to human native vessels. This review presents an overview of fabrication techniques and novel applications of polymer blends and polymer composites in cardiovascular implants, ranging from coronary stents to tissue engineered constructs.