Manufacturing of hydrogel biomaterials with controlled mechanical properties for tissue engineering applications.

Hydrogels have been recognized as crucial biomaterials in the field of tissue engineering, regenerative medicine, and drug delivery applications due to their specific characteristics. These biomaterials benefit from retaining a large amount of water, effective mass transfer, similarity to natural tissues and the ability to form different shapes. However, having relatively poor mechanical properties is a limiting factor associated with hydrogel biomaterials. Controlling the biomechanical properties of hydrogels is of paramount importance. In this work, firstly, mechanical characteristics of hydrogels and methods employed for characterizing these properties are explored. Subsequently, the most common approaches used for tuning mechanical properties of hydrogels including but are not limited to, interpenetrating polymer networks, nanocomposites, self-assembly techniques, and co-polymerization are discussed. The performance of different techniques used for tuning biomechanical properties of hydrogels is further compared. Such techniques involve lithography techniques for replication of tissues with complex mechanical profiles; microfluidic techniques applicable for generating gradients of mechanical properties in hydrogel biomaterials for engineering complex human tissues like intervertebral discs, osteochondral tissues, blood vessels and skin layers; and electrospinning techniques for synthesis of hybrid hydrogels and highly ordered fibers with tunable mechanical and biological properties. We finally discuss future perspectives and challenges for controlling biomimetic hydrogel materials possessing proper biomechanical properties. STATEMENT OF SIGNIFICANCE: Hydrogels biomaterials are essential constituting components of engineered tissues with the applications in regenerative medicine and drug delivery. The mechanical properties of hydrogels play crucial roles in regulating the interactions between cells and extracellular matrix and directing the cells phenotype and genotype. Despite significant advances in developing methods and techniques with the ability of tuning the biomechanical properties of hydrogels, there are still challenges regarding the synthesis of hydrogels with complex mechanical profiles as well as limitations in vascularization and patterning of complex structures of natural tissues which barricade the production of sophisticated organs. Therefore, in addition to a review on advanced methods and techniques for measuring a variety of different biomechanical characteristics of hydrogels, the new techniques for enhancing the biomechanics of hydrogels are presented. It is expected that this review will profit future works for regulating the biomechanical properties of hydrogel biomaterials to satisfy the demands of a variety of different human tissues.

Microfluidic-Based Multi-Organ Platforms for Drug Discovery.

Development of predictive multi-organ models before implementing costly clinical trials is central for screening the toxicity, efficacy, and side effects of new therapeutic agents. Despite significant efforts that have been recently made to develop biomimetic in vitro tissue models, the clinical application of such platforms is still far from reality. Recent advances in physiologically-based pharmacokinetic and pharmacodynamic (PBPK-PD) modeling, micro- and nanotechnology, and in silico modeling have enabled single- and multi-organ platforms for investigation of new chemical agents and tissue-tissue interactions. This review provides an overview of the principles of designing microfluidic-based organ-on-chip models for drug testing and highlights current state-of-the-art in developing predictive multi-organ models for studying the cross-talk of interconnected organs. We further discuss the challenges associated with establishing a predictive body-on-chip (BOC) model such as the scaling, cell types, the common medium, and principles of the study design for characterizing the interaction of drugs with multiple targets.

Surface morphology and properties of ternary polymer blends: effect of the migration of minor components.

In this work, the surface morphology and properties of ternary polymer blends and the migration of minor component molecules to the top surface layer of the films were studied. We used polystyrene (PS), poly(butylene adipate-co-terephthalate), polycaprolactone, poly(methyl methacrylate), and polylactide as second minor phases in a blend of polyethylene terephthalate-poly(ethylene glycol) (PET-PEG). The morphology of the ternary systems predicted using the spreading coefficient and relative interfacial energy concepts was confirmed by scanning electron microscopy images. The surface characterization results showed a higher rate of migration of PEG to the polymer-air interface in the systems with a nonwetting morphology and the highest in the PET-PS-PEG blend. Atomic force microscopy images suggested that the high surface hydrophilicity of the PET-PS-PEG blend is due to a dendritic pattern of PEG crystals on the film surface, which were not observed for the other samples.

Surface roughening of PET films through blend phase coarsening.

In this study, a novel method to increase the surface roughness of polyethylene terephthalate (PET) films is proposed. The mechanism of phase coarsening at the surface in extruded thin films of PET blended with low concentrations of polystyrene (PS) was investigated. A small amount of poly(hyroxyl ether) of bisphenol A (phenoxy resin, PKHH) was found to significantly increase the surface roughness due to its effect on the PS-PET interfacial tension. X-ray photoelectron spectroscopy (XPS) results indicated that in the presence of PKHH, PS droplets migrated spontaneously towards the surface of the polymer film. An increased local concentration of PS near the surface took the form of encapsulated droplets. Above the flow temperature of the blend, the local concentration of PS eventually reached a level where a co-continuous morphology occurred, resulting in the instabilities on the surface of the film. The adhesion properties of films with various roughnesses were determined using a pull-off test and found to be significantly increased, which suggested that co-continuous morphology and the coarsening process increased the adhesive properties of the film.