Skeletal muscle tissue engineering aims to fabricate tissue constructs to replace or restore diseased or injured skeletal muscle tissues in the body. Several biomaterials and microscale technologies ...have been used in muscle tissue engineering. However, it is still challenging to mimic the function and structure of the native muscle tissues. Three-dimensional (3D) bioprinting is a powerful tool to mimic the hierarchical structure of native tissues. Here, 3D bioprinting was used to fabricate tissue constructs using gelatin methacryloyl (GelMA)-alginate bioinks. Mechanical and rheological properties of GelMA-alginate hydrogels were characterized. C2C12 myoblasts at the density 8 × 106 cells/mL were used as the cell model. The effects of alginate concentration (0, 6, and 8% (w/v)) and crosslinking mechanism (UV crosslinking or ionic crosslinking with UV crosslinking) on printability, cell viability, proliferation, and differentiation of bioinks were studied. The results showed that 10% (w/v) GelMA-8% (w/v) alginate crosslinked using UV light and 0.1 M CaCl2 provided the optimum niche to induce muscle tissue formation compared to other hydrogel compositions. Furthermore, metabolic activity of cells in GelMA bioinks was improved by addition of oxygen-generating particles to the bioinks. It is hoped that such bioprinted muscle tissues may find wide applications in drug screening and tissue regeneration.
Poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles (NPs) are commonly used for drug delivery because of their favored biocompatibility and suitability for sustained and controlled drug release. To ...prolong NP circulation time, enable target‐specific drug delivery and overcome physiological barriers, NPs camouflaged in cell membranes have been developed and evaluated to improve drug delivery. Here, we discuss recent advances in cell membrane‐coated PLGA NPs, their preparation methods, and their application to cancer therapy, management of inflammation, treatment of cardiovascular disease and control of infection. We address the current challenges and highlight future research directions needed for effective use of cell membrane‐camouflaged NPs.
Extracellular vesicles (EVs) are cell-derived nanostructures that mediate intercellular communication by delivering complex signals in normal tissues and cancer. The cellular coordination required ...for tumor development and maintenance is mediated, in part, through EV transport of molecular cargo to resident and distant cells. Most studies on EV-mediated signaling have been performed in two-dimensional (2D) monolayer cell cultures, largely because of their simplicity and high-throughput screening capacity. Three-dimensional (3D) cell cultures can be used to study cell-to-cell and cell-to-matrix interactions, enabling the study of EV-mediated cellular communication. 3D cultures may best model the role of EVs in formation of the tumor microenvironment (TME) and cancer cell-stromal interactions that sustain tumor growth. In this review, we discuss EV biology in 3D culture correlates of the TME. This includes EV communication between cell types of the TME, differences in EV biogenesis and signaling associated with differing scaffold choices and in scaffold-free 3D cultures and cultivation of the premetastatic niche. An understanding of EV biogenesis and signaling within a 3D TME will improve culture correlates of oncogenesis, enable molecular control of the TME and aid development of drug delivery tools based on EV-mediated signaling.
There is a pressing need for effective therapeutics for coronavirus disease 2019 (COVID-19), the respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The ...process of drug development is a costly and meticulously paced process, where progress is often hindered by the failure of initially promising leads. To aid this challenge, in vitro human microphysiological systems need to be refined and adapted for mechanistic studies and drug screening, thereby saving valuable time and resources during a pandemic crisis. The SARS-CoV-2 virus attacks the lung, an organ where the unique three-dimensional (3D) structure of its functional units is critical for proper respiratory function. The in vitro lung models essentially recapitulate the distinct tissue structure and the dynamic mechanical and biological interactions between different cell types. Current model systems include Transwell, organoid and organ-on-a-chip or microphysiological systems (MPSs). We review models that have direct relevance toward modeling the pathology of COVID-19, including the processes of inflammation, edema, coagulation, as well as lung immune function. We also consider the practical issues that may influence the design and fabrication of MPS. The role of lung MPS is addressed in the context of multi-organ models, and it is discussed how high-throughput screening and artificial intelligence can be integrated with lung MPS to accelerate drug development for COVID-19 and other infectious diseases.
Three-dimensional (3D) bioprinting has demonstrated great potential for the fabrication of biomimetic human tissues and complex graft materials. This technology utilizes bioinks composed of cellular ...elements placed within a biomaterial. Mesenchymal stromal cells (MSCs) are an attractive option for cell selection in 3D bioprinting. MSCs can be isolated from a variety of tissues, can pose vast proliferative capacity and can differentiate to multiple committed cell types. Despite their promising properties, the use of MSCs has been associated with several drawbacks. These concerns are related to the ex vivo manipulation throughout the process of 3D bioprinting. The herein manuscript aims to present the current evidence surrounding these events and propose ways to minimize the risks to the patients following widespread expansion of 3D bioprinting in the medical field.
Implants made of poly(lactide-co-glycolide) (PLGA) are biodegradable and frequently provoke foreign body reactions (FBR) in the host tissue. In order to modulate the inflammatory response of the host ...tissue, PLGA implants can be loaded with anti-inflammatory drugs. The aim of this study was to analyze the impact of PLGA 80/20 rods loaded with the diclofenac sodium (DS) on local tissue reactions in the femur of rats. Special emphasis was put on bone regeneration and the presence of multinucleated giant cells (MGCs) associated with FBR. PLGA 80/20 alone and PLGA 80/20 combined with DS was extruded into rods. PLGA rods loaded with DS (PLGA+DS) were implanted into the femora of 18 rats. Eighteen control rats received unloaded PLGA rods. The follow-up period was of 3, 6 and 12 weeks. Each group comprised of six rats. Peri-implant tissue reactions were histologically and histomorphometrically evaluated. The implantation of PLGA and PLGA+DS8 rods induced the formation of a layer of newly formed bone islands parallel to the contour of the implants. PLGA+DS rods tended to reduce the presence of multi-nucleated giant cells (MGCs) at the implant surface. Although it is known that the systemic administration of DS is associated with compromised bone healing, the local release of DS via PLGA rods did not have negative effects on bone regeneration in the femora of rats throughout 12 weeks.
Currently, there are more than 1.5 million knee and hip replacement procedures carried out in the United States. Implants have a 10-15-year lifespan with up to 30% of revision surgeries showing ...complications with osteomyelitis. Titanium and titanium alloys are the favored implant materials because they are lightweight and have high mechanical strength. However, this increased strength can be associated with decreased bone density around the implant, leading to implant loosening and failure. To avoid this, current strategies include plasma-spraying titanium surfaces and foaming titanium. Both techniques give the titanium a rough and irregular finish that improves biocompatibility. Recently, researchers have also sought to surface-conjugate proteins to titanium to induce osteointegration. Cell adhesion-promoting proteins can be conjugated to methacrylate groups and crosslinked using a variety of methods. Methacrylated proteins can be conjugated to titanium surfaces through atom transfer radical polymerization (ATRP). However, surface conjugation of proteins increases biocompatibility non-specifically to bone cells, adding to the risk of biofouling which may result in osteomyelitis that causes implant failure. In this work, we analyze the factors contributing to biofouling when coating titanium to improve biocompatibility, and design an experimental scheme to evaluate optimal coating parameters.
Monitoring changes in edema-associated intracranial pressure that complicates trauma or surgery would lead to improved outcomes. Implantable pressure sensors have been explored, but these sensors ...require post-surgical removal, leading to the risk of injury to brain tissue. The use of biodegradable implantable sensors would help to eliminate this risk. Here, we demonstrate a bioactive glass (BaG)-based hydration sensor. Fluorine (CaF
) containing BaG (BaG-F) was produced by adding 5, 10 or 20 wt.% of CaF
to a BaG matrix using a melting manufacturing technique. The structure, morphology and electrical properties of the resulting constructs were evaluated to understand the physical and electrical behaviors of this BaG-based sensor. Synthesis process for the production of the BaG-F-based sensor was validated by assessing the structural and electrical properties. The structure was observed to be amorphous and dense, the porosity decreased and grain size increased with increasing CaF
content in the BaG matrix. We demonstrated that this BaG-F chemical composition is highly sensitive to hydration, and that the electrical sensitivity (resistive-capacitive) is induced by hydration and reversed by dehydration. These properties make BaG-F suitable for use as a humidity sensor to monitor brain edema and, consequently, provide an alert for increased intracranial pressure.
Derived Hench bioactive glass (BaG) containing boron (B) is explored in this work as it plays an important role in bone development and regeneration. B was also found to enhance BaG dissociation. ...However, it is only possible to incorporate a limited amount of B. To increase the amount of B in BaG, bioactive borosilicate glasses (BaG-B
) were fabricated based on the use of the solution-gelation process (sol-gel). In this work, a high B content (20 wt.%) in BaG, respecting the conditions of bioactivity and biodegradability required by Hench, was achieved for the first time. The capability of BaG-B
to form an apatite phase was assessed in vitro by immersion in simulated body fluid (SBF). Then, the chemical structure and the morphological changes in the fabricated BaG-B
(x = 0, 5, 10 and 20) were studied. The formation of hydroxyapatite (HAp) layer was observed with X-ray diffraction (XRD) and infrared (IR) spectroscopy. The presence of HAp layer was confirmed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Enhanced bioactivity and chemical stability of BaG-B
were evaluated with an ion exchange study based on Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES) and energy dispersive spectroscopy (EDS). Results indicate that by increasing the concentration of B in BaG-Bx, the crystallization rate and the quality of the newly formed HAp layer on BaG-B
surfaces can be improved. The presence of B also leads to enhanced degradation of BaGs in SBF. Accordingly, BAG-B
can be used for bone regeneration, especially in children, because of its faster degradation as compared to B-free glass.
Activation of endothelial cells following severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection is thought to be the primary driver for the increasingly recognized thrombotic ...complications in coronavirus disease 2019 patients, potentially due to the SARS‐CoV‐2 Spike protein binding to the human angiotensin‐converting enzyme 2 (hACE2). Vaccination therapies use the same Spike sequence or protein to boost host immune response as a protective mechanism against SARS‐CoV‐2 infection. As a result, cases of thrombotic events are reported following vaccination. Although vaccines are generally considered safe, due to genetic heterogeneity, age, or the presence of comorbidities in the population worldwide, the prediction of severe adverse outcome in patients remains a challenge. To elucidate Spike proteins underlying patient‐specific‐vascular thrombosis, the human microcirculation environment is recapitulated using a novel microfluidic platform coated with human endothelial cells and exposed to patient specific whole blood. Here, the blood coagulation effect is tested after exposure to Spike protein in nanoparticles and Spike variant D614G in viral vectors and the results are corroborated using live SARS‐CoV‐2. Of note, two potential strategies are also examined to reduce blood clot formation, by using nanoliposome‐hACE2 and anti‐Interleukin (IL) 6 antibodies.
SARS‐CoV‐2 infection drives the increasingly recognized thrombotic complications in COVID‐19 patients, potentially due to the SARS‐CoV‐2 Spike protein binding to human angiotensin‐converting enzyme 2. Vaccination therapies that are spike‐based can lead to a similar outcomes. Endothelialized channels exposed to patient specific blood in microfluidic platforms can be used to rapidly test for blood coagulation, predicting thrombotic events.
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