Bioprinting holds great promise toward engineering functional cardiac tissue constructs for regenerative medicine and as drug test models. However, it is highly limited by the choice of inks that ...require maintaining a balance between the structure and functional properties associated with the cardiac tissue. In this regard, a novel and mechanically robust biomaterial‐ink based on nonmulberry silk fibroin protein is developed. The silk‐based ink demonstrates suitable mechanical properties required in terms of elasticity and stiffness (≈40 kPa) for developing clinically relevant cardiac tissue constructs. The ink allows the fabrication of stable anisotropic scaffolds using a dual crosslinking method, which are able to support formation of aligned sarcomeres, high expression of gap junction proteins as connexin‐43, and maintain synchronously beating of cardiomyocytes. The printed constructs are found to be nonimmunogenic in vitro and in vivo. Furthermore, delving into an innovative method for fabricating a vascularized myocardial tissue‐on‐a‐chip, the silk‐based ink is used as supporting hydrogel for encapsulating human induced pluripotent stem cell derived cardiac spheroids (hiPSC‐CSs) and creating perfusable vascularized channels via an embedded bioprinting technique. The ability is confirmed of silk‐based supporting hydrogel toward maturation and viability of hiPSC‐CSs and endothelial cells, and for applications in evaluating drug toxicity.
In this work, a novel nonmulberry silk based biomaterial‐ink is reported for developing mechanically robust and clinically relevant cardiac patches. Both anisotropic avascular constructs for mimicking the native tissue structure, as well as vascularized constructs using an innovative embedded bioprinting technology are fabricated using the designed ink. The vascularized constructs along with a microfluidic system offer great potential for drug screening platforms.
Developing biomimetic cartilaginous tissues that support locomotion while maintaining chondrogenic behavior is a major challenge in the tissue engineering field. Specifically, while locomotive forces ...demand tissues with strong mechanical properties, chondrogenesis requires a soft microenvironment. To address this challenge, 3D cartilage‐like tissue is fabricated using two biomaterials with different mechanical properties: a hard biomaterial to reflect the macromechanical properties of native cartilage, and a soft biomaterial to create a chondrogenic microenvironment. To this end, a bath composed of an interpenetrating polymer network (IPN) of polyethylene glycol (PEG) and alginate hydrogel (MPa order compressive modulus) is developed as an extracellular matrix (ECM) with self‐healing properties. Within this bath supplemented with thrombin, human mesenchymal stem cell (hMSC) spheroids embedded in fibrinogen are 3D bioprinted, creating a soft microenvironment composed of fibrin (kPa order compressive modulus) that simulate cartilage's pericellular matrix and allow a fast diffusion of nutrients. The bioprinted hMSC spheroids present high viability and chondrogenic‐like behavior without adversely affecting the macromechanical properties of the tissue. Therefore, the ability to locally bioprint a soft and cell stimulating biomaterial inside of a mechanically robust hydrogel is demonstrated, thereby uncoupling the micro‐ and macromechanical properties of the 3D printed tissues such as cartilage.
In this work, 3D bioprinting technology is used to develop a biomimetic cartilage‐like tissue with near‐paradoxical mechanical properties, being soft at the cellular level, due to the soft bioink composed of human bone marrow mesenchymal stem cells in the form of spheroids embedded in fibrinogen, and the stiff polyethylene glycol and alginate bath, showing great potential for cartilage regeneration studies.
Fibrin gel has been widely used for engineering various types of tissues due to its biocompatible nature, biodegradability, and tunable mechanical and nanofibrous structural properties. Despite their ...promising regenerative capacity and extensive biocompatibility with various tissue types, fibrin-based biomaterials are often notoriously known as burdensome candidates for 3D biofabrication and bioprinting. The high viscosity of fibrin (crosslinked form) hinders proper ink extrusion, and its pre-polymer form, fibrinogen, is not capable of maintaining shape fidelity. To overcome these limitations and empower fibrinogen-based bioinks for fibrin biomimetics and regenerative applications, different strategies can be practiced. The aim of this review is to report the strategies that bring fabrication compatibility to these bioinks through mixing fibrinogen with printable biomaterials, using supporting bath supplemented with crosslinking agents, and crosslinking fibrin in situ. Moreover, the review discusses some of the recent advances in 3D bioprinting of biomimetic soft and hard tissues using fibrinogen-based bioinks, and highlights the impacts of these strategies on fibrin properties, its bioactivity, and the functionality of the consequent biomimetic tissue.
Statement of Significance
Due to its biocompatible nature, biodegradability, and tunable mechanical and nanofibrous structural properties, fibrin gel has been widely employed in tissue engineering and more recently, used as in 3D bioprinting. The fibrinogen's poor printable properties make it difficult to maintain the 3D shape of bioprinted constructs. Our work describes the strategies employed in tissue engineering to allow the 3D bioprinting of fibrinogen-based bioinks, such as the combination of fibrinogen with printable biomaterials, the in situ fibrin crosslinking, and the use of supporting bath supplemented with crosslinking agents. Further, this review discuss the application of 3D bioprinting technology to biofabricate fibrin-based soft and hard tissues for biomedical applications, and discuss current limitations and future of such in vitro models.
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Treatment of injured peripheral nerves, especially long-distance nerve defects, remains a significant challenge in regenerative medicine due to complex biological conditions and a lack of ...biomaterials for effective nerve reconstruction. Without proper treatment, nerve injury leads to motor and sensory dysfunction. Here, we have developed an efficacious nerve allograft treated with a dual drug containing acrolimus and nerve growth factor to bridge the nerve gap and achieve rapid neural tissue recovery without immunological rejection. The recovery of the structure, activity, and function of rats treated with the dual drug-treated allograft was investigated by walking track analysis and electrophysiological measurement. The sciatic functional index was measured to be -3.0 after a 12-week treatment. The nerve conduction velocity, peak latency, and peak amplitude of the nerve action potentials demonstrate the functional recovery of the nerve. To study the synergistic effect of the dual drug on the growth of neurites, a neural cell hypoxia model was created. The dual drug exhibited a high efficiency in promoting the growth of nerve cells under the nerve injury-induced hypoxic condition. The dual drug could protect the cells against antioxidative damage from hypoxia by the expression of heat shock protein, hypoxia-inducible factor, β-tubulin, and vimentin.
The pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is receiving worldwide attention, due to the severity of the disease (COVID-19) that resulted in more than a ...million global deaths so far. The urgent need for vaccines and antiviral drugs is mobilizing the scientific community to develop strategies for studying the mechanisms of SARS-CoV-2 infection, replication kinetics, pathogenesis, host–virus interaction, and infection inhibition. In this work, we review the strategies of tissue engineering in the fabrication of three-dimensional (3D) models used in virology studies, which presented many advantages over conventional cell cultures, such as complex cytoarchitecture and a more physiological microenvironment. Scaffold-free (spheroids and organoids) and scaffold-based (3D scaffolding and 3D bioprinting) approach allow the biofabrication of more realistic models relevant to the pandemic, to be used as in vitro platforms for the development of new vaccines and therapies against COVID-19.
In article number 1907436, Biman B. Mandal, Su Ryon Shin, and co‐workers develop a non‐mulberry silk‐based ink for fabricating tough and flexible cardiac patches. The silk‐based ink has also ...facilitated the development of 3D endothelialized myocardial constructs that could potentially be used for an organ‐on‐a‐chip model as a drug screening platform.
The effects of ethanol/broth proportions and the number of steps at varying pH in the presence or absence of sodium chloride (NaCl) were studied as precipitation strategies for the recovery and ...purification of high molar mass bio-hyaluronic acid (Bio-HA). Bio-HA was synthesized by
Streptococcus zooepidemicus
in a culture medium containing glucose and soy peptones. A single-step precipitation was more attractive than multistep precipitation in terms of recovery and purity as well as decreased use of ethanol. The best conditions in the absence and presence of salt were 2:1 ethanol/broth (
v
/
v
) at pH 4 (55.0 ± 0.2% purity and 85.0 ± 0.7% recovery) and 2:1 ethanol/broth (
v
/
v
) at pH 7 + 2 mol L
−1
NaCl (59.0 ± 0.9% purity and 82.0 ± 4.3% recovery). Dynamic light scattering (DLS) spectra showed different particle sizes as a consequence of the changes in the molecular structure of HA, mainly with changes in pH. Although slight changes in distribution were observed, the average HA molar mass was not affected by the precipitation strategy, remaining on the order of 10
5
Da. Therefore, pH and NaCl modulated the precipitation performance of HA. These findings are relevant to further optimizing the precipitation step, thus minimizing costs in the later stages of HA purification.
Recent studies have demonstrated that cannabinoids are potentially effective in the treatment of various neurological conditions, and cannabidiol (CBD), one of the most studied compounds, has been ...proposed as a non-toxic option. However, the adverse effects of CBD on neurodevelopmental processes have rarely been studied in cell culture systems. To better understand CBD’s influence on neurodevelopment, we exposed neural progenitor cells (NPCs) to different concentrations of CBD (1 µM, 5 µM, and 10 µM). We assessed the morphology, migration, differentiation, cell death, and gene expression in 2D and 3D bioprinted models to stimulate physiological conditions more effectively. Our results showed that CBD was more toxic at higher concentrations (5 µM and 10 µM) and affected the viability of NPCs than at lower concentrations (1 µM), in both 2D and 3D models. Moreover, our study revealed that higher concentrations of CBD drastically reduced the size of neurospheres and the number of NPCs within neurospheres, impaired the morphology and mobility of neurons and astrocytes after differentiation, and reduced neurite sprouting. Interestingly, we also found that CBD alters cellular metabolism by influencing the expression of glycolytic and β-oxidative enzymes in the early and late stages of metabolic pathways. Therefore, our study demonstrated that higher concentrations of CBD promote important changes in cellular functions that are crucial during CNS development.
In article number 1906330, Jeroen Leijten, Su Ryon Shin, and co‐workers develop 3D cartilage‐like tissue through local bioprinting of mesenchymal stem cell spheroids laden with soft and cell ...stimulating bioink within a mechanically robust hydrogel. This uncoupling of the micro and macro mechanical properties of the 3D printed construct allows it to possess both a chondrogenic microenvironment and the ability to withstand mechanical loads.
Polymeric nanocapsules with elastic characteristics were prepared by the pre-formed polymer interfacial deposition method. The system consists of an oily core of retinyl palmitate with Span 60 and a ...polymeric wall of poly(
d,
l-lactide) (PLA). A narrow size distribution (215
nm, P.D.I. 0.10) was showed by dynamic light scattering (DLS) analyses. Particle deformability was observed by transmission electron microscopy (TEM) images and permeation of the particles through two superposed membranes of smaller pore diameters. Permeation studies were achieved using plastic surgery abdominal human skin by Franz diffusion cell. Retinyl palmitate permeates into deep skin layers. Besides, a PLA fluorescent derivative conjugated with Nile blue dye by an amide covalent bound was additionally obtained. Permeation profile of the nanocapsules with the fluorescent polymer was evaluated by confocal laser scanning microscopy (CLSM). The CLSM showed that nanocapsules were distributed uniformly, suggesting that the permeation mechanism through skin is intercellular. Thus, the use of these nanocapsules may be a feasible strategy to enhance the permeation of actives into the skin when delivery to deep layers is aimed.
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