Search

Rising maternal mortality rates in the U.S. are a significant public health issue that must be addressed; however, much of the basic science information required to target pregnancy-related pathologies have not yet been defined. Placental and blastocyst implantation research are challenging to perform in humans because of the early time frame of these processes in pregnancy and limited access to first trimester tissues. As a result, there is a critical need to develop model systems capable of studying these processes in increasing mechanistic detail. With the recent passing of the FDA Modernization Act 2.0 and advances in tissue engineering methods, three-dimensional microphysiological model systems offer an exciting opportunity to model early stages of placentation. Here, we detail the synthesis, characterization, and application of gelatin methacryloyl (GelMA) hydrogel platforms for studying trophoblast behavior in three-dimensional hydrogel systems. Photopolymerization strategies to fabricate GelMA hydrogels render the hydrogels homogeneous in terms of structure and stable under physiological temperatures, allowing for rigorous fabrication of reproducible hydrogel variants. Unlike other natural polymers that have minimal opportunity to tune their properties, GelMA hydrogel properties can be tuned across many axes of variation, including polymer degree of functionalization, gelatin bloom strength, light exposure time and intensity, polymer weight percent, photoinitiator concentration, and physical geometry. In this work, we aim to inspire and instruct the field to utilize GelMA biomaterial strategies for future placental research. With enhanced microphysiological models of pregnancy, we can now generate the basic science information required to address problems in pregnancy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Samantha Zambuto reports financial support was provided by National Institutes of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cartilage wounds result in chronic pain and degradation of the quality of life for millions of people. A synthetic cellular scaffold able to heal the damage by substituting the natural tissue is of great potential value. Here, it is shown for the first time that the unique interplay between the molecular components of cartilage can be reproduced in composite materials made of a polyelectrolyte hydrogel embedding a collagen scaffold. These composites possess a mechanical response determined by osmotic and electrostatic effects, comparable to articular cartilage in terms of elastic modulus, time-dependent response, and permeability to interstitial fluid flow. Made entirely from biocompatible materials, the cartilage-like composite materials developed permit 3D culture of chondrocyte-like cells through their microporosity. The biomimetic materials presented here constitute an entirely new class of osmotically stiffened composites, which may find use outside of biomedical applications., (© 2018 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Mechanically robust hydrogels are required for many tissue engineering applications to serve as cell-supporting structures. Unlike natural tissues, the majority of existing tough hydrogels lack ordered microstructures organized to withstand specific loading conditions. In this work, electrospun gelatin nanofibres, mimicking the collagen network in native tissues, are used to strengthen and resist crack propagation in brittle alginate hydrogels. Aligned nanofibre reinforcement enhances the tensile strength of the hydrogels by up to two orders of magnitude. The nanofibres can be arranged as multilayer laminates with varying orientations, which increases the toughness by two orders of magnitude compared with the unreinforced hydrogel. This work demonstrates a two-part strategy of fibre reinforcement and composite lamination in manufacturing strong and tough hydrogels with flexible microstructures to suit different mechanical and biomedical requirements., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Severe degeneration of the intervertebral disc has an immensely debilitating effect on quality of life that has become a serious health and economic burden throughout the world. The disc plays an integral role in biomechanical movement and support within the spine. The emergence of tissue engineering endeavours to restore the structural characteristics and functionality of the native tissue. Hydrogels have been widely investigated as a candidate for regeneration of the gelatinous nucleus pulposus due to its architectural resemblance and fluid retention characteristics. However, hydrogels are often limited due to small compressive stiffness and tear resistance, leading to extrusion complications. Reinforcement of the hydrogel network using polymeric scaffolds may address these issues of inadequate mechanical properties and implant instability. This study investigates the potential of a carrageenan gel-infused polycaprolactone scaffold for nucleus pulposus tissue engineering. Mechanical properties were characterised using viscoelastic and poroelastic frameworks via microindentation. The incorporation of polymeric reinforcement within the gels increased material stiffness to that comparable to the native nucleus pulposus, however permeability was significantly greater than native values. A preliminary cell evaluation culturing NIH 3T3s over 21 days suggested the incorporation of polymeric networks also enhanced cellular proliferation compared to gels alone., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The microenvironment, which can be considered the sum of all the components and conditions surrounding a particular cell, is critical to moderating cellular behavior. In bone, interactions with the microenvironment can influence osteogenic differentiation, and subsequent extracellular matrix deposition, mineralization, and bone growth. Beyond regenerative medicine purposes, tissue engineering tools, namely cell-scaffold constructs, can be used as models of the bone microenvironment. Hydrogels, which are hydrophilic polymer networks, are popularly used for cell culture constructs due to their substantial water content and their ability to be tailored for specific applications. As synthetic microenvironments, a level of control can be exerted on the hydrogel structure and material properties, such that individual contributions from the scaffold on cellular behavior can be observed. Both biochemical and mechanical stimuli have been shown to modulate cellular behaviors. Hydrogels can be modified to present cell-interactive ligands, include osteoinductive moieties, vary mechanical properties, and be subject to external mechanical stimulation, all of which have been shown to affect osteogenic differentiation. Following "bottom-up" fabrication methods, levels of complexity can be introduced to hydrogel systems, such that the synergistic effects of multiple osteogenic cues can be observed. This review explores the utility of hydrogel scaffolds as synthetic bone microenvironments to observe both individual and synergistic effects from biochemical and mechanical signals on osteogenic differentiation. Ultimately, a better understanding of how material properties can influence cellular behavior will better inform design of tissue engineering scaffolds, not just for studying cell behavior, but also for regenerative medicine purposes., (© Georg Thieme Verlag KG Stuttgart · New York.)

Mechanically robust and biomimicking scaffolds are needed for structural engineering of tissues such as the intervertebral disc, which are prone to failure and incapable of natural healing. Here, the formation of thick, randomly aligned polycaprolactone electrospun fibre structures infiltrated with alginate is reported. The composites are characterised using both indentation and tensile testing and demonstrate substantially different tensile and compressive moduli. The composites are mechanically robust and exhibit large strains-to-failure, exhibiting toughening mechanisms observed in other composite material systems. The method presented here provides a way to create large-scale biomimetic scaffolds that more closely mimic the composite structure of natural tissue, with tuneable tensile and compressive properties via the fibre and matrix phases, respectively.

A severe shortage of donor cornea is now an international crisis in public health. Substitutes for donor tissue need to be developed to meet the increasing demand for corneal transplantation. Current attempts in designing scaffolds for corneal tissue regeneration involve utilization of expensive materials. Yet, these corneal scaffolds still lack the highly-organized fibrous structure that functions as a load-bearing component in the native tissue. This work shows that transparent nanofiber-reinforced hydrogels could be developed from cheap, non-immunogenic and readily available natural polymers to mimic the cornea's microstructure. Electrospinning was employed to produce gelatin nanofibers, which were then infiltrated with alginate hydrogels. Introducing electrospun nanofibers into hydrogels improved their mechanical properties by nearly one order of magnitude, yielding mechanically robust composites. Such nanofiber-reinforced hydrogels could serve as alternatives to donor tissue for corneal transplantation.

Tissue engineering offers a paradigm shift in the treatment of back pain. Engineered intervertebral discs could replace degenerated tissue and overcome the limitations of current treatments, which substantially alter the biomechanical properties of the spine. The centre of the disc, the nucleus pulposus, is an amorphous gel with a large bound water content and it can resist substantial compressive loads. Due to similarities in their compositions, hydrogels have frequently been considered as substitutes for the nucleus pulposus. However, there has been limited work characterising the time-dependent mechanical behaviour of hydrogel scaffolds for nucleus pulposus tissue engineering. Poroelastic behaviour, which plays a key role in nutrient transport, is of particular importance. Here, we investigate the time-dependent mechanical properties of gelatin and agar hydrogels and of gelatin-agar composites. The time-dependent properties of these hydrogels are explored using viscoelastic and poroelastic frameworks. Several gel formulations demonstrate comparable equilibrium elastic behaviour to the nucleus pulposus under unconfined compression, but permeability values that are much greater than those of the native tissue. A range of time-dependent responses are observed in the composite gels examined, presenting the opportunity for targeted design of custom hydrogels with combinations of mechanical properties optimized for tissue engineering applications., (Copyright © 2011 Elsevier Ltd. All rights reserved.)