Composite Bioscaffolds Incorporating Decellularized ECM as a Cell-Instructive Component Within Hydrogels as In Vitro Models and Cell Delivery Systems

Author(s):  
Arthi Shridhar ◽  
Elizabeth Gillies ◽  
Brian G. Amsden ◽  
Lauren E. Flynn
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Hee-Gyeong Yi ◽  
Hyeonji Kim ◽  
Junyoung Kwon ◽  
Yeong-Jin Choi ◽  
Jinah Jang ◽  
...  

AbstractRapid development of vaccines and therapeutics is necessary to tackle the emergence of new pathogens and infectious diseases. To speed up the drug discovery process, the conventional development pipeline can be retooled by introducing advanced in vitro models as alternatives to conventional infectious disease models and by employing advanced technology for the production of medicine and cell/drug delivery systems. In this regard, layer-by-layer construction with a 3D bioprinting system or other technologies provides a beneficial method for developing highly biomimetic and reliable in vitro models for infectious disease research. In addition, the high flexibility and versatility of 3D bioprinting offer advantages in the effective production of vaccines, therapeutics, and relevant delivery systems. Herein, we discuss the potential of 3D bioprinting technologies for the control of infectious diseases. We also suggest that 3D bioprinting in infectious disease research and drug development could be a significant platform technology for the rapid and automated production of tissue/organ models and medicines in the near future.


Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3295
Author(s):  
Federica Foglietta ◽  
Loredana Serpe ◽  
Roberto Canaparo

Stimuli-responsive drug-delivery systems (DDSs) have emerged as a potential tool for applications in healthcare, mainly in the treatment of cancer where versatile nanocarriers are co-triggered by endogenous and exogenous stimuli. Two-dimensional (2D) cell cultures are the most important in vitro model used to evaluate the anticancer activity of these stimuli-responsive DDSs due to their easy manipulation and versatility. However, some limitations suggest that these in vitro models poorly predict the outcome of in vivo studies. One of the main drawbacks of 2D cell cultures is their inadequate representation of the 3D environment’s physiological complexity, which sees cells interact with each other and the extracellular matrix (ECM) according to their specific cellular organization. In this regard, 3D cancer models are a promising approach that can overcome the main shortcomings of 2D cancer cell cultures, as these in vitro models possess many peculiarities by which they mimic in vivo tumors, including physiologically relevant cell–cell and cell–ECM interactions. This is, in our opinion, even more relevant when a stimuli-responsive DDS is being investigated. In this review, we therefore report and discuss endogenous and exogenous stimuli-responsive DDSs whose effectiveness has been tested using 3D cancer cell cultures.


2021 ◽  
Author(s):  
Rachel M McLaughlin ◽  
Amanda Laguna ◽  
Ilayda Top ◽  
Christien Hernadez ◽  
Liane L Livi ◽  
...  

Stroke is a devastating neurological disorder and a leading cause of death and long-term disability. Despite many decades of research, there are still very few therapeutic options for patients suffering from stroke or its consequences. This is partially due to the limitations of current research models, including traditional in vitro models which lack the three-dimensional (3D) architecture and cellular make-up of the in vivo brain. 3D spheroids derived from primary postnatal rat cortex provide an in vivo-relevant model containing a similar cellular composition to the native cortex and a cell-synthesized extracellular matrix. These spheroids are cost-effective, highly reproducible, and can be produced in a high-throughput manner, making this model an ideal candidate for screening potential therapeutics. To study the cellular and molecular mechanisms of stroke in this model, spheroids were deprived of glucose, oxygen, or both oxygen and glucose for 24 hours. Both oxygen and oxygen-glucose deprived spheroids demonstrated many of the hallmarks of stroke, including a decrease in metabolism, an increase in neural dysfunction, and an increase in reactive astrocytes. Pretreatment of spheroids with the antioxidant agent N-acetylcysteine (NAC) mitigated the decrease in ATP seen after 24 hours of oxygen-glucose deprivation. Together, these results show the utility of our 3D cortical spheroid model for studying ischemic injury and its potential for screening stroke therapeutics.


2003 ◽  
Vol 83 (3) ◽  
pp. 871-932 ◽  
Author(s):  
PAMELA L. TUMA ◽  
ANN L. HUBBARD

Tuma, Pamela L., and Ann L. Hubbard. Transcytosis: Crossing Cellular Barriers. Physiol Rev 83: 871–932, 2003; 10.1152/physrev.00001.2003.—Transcytosis, the vesicular transport of macromolecules from one side of a cell to the other, is a strategy used by multicellular organisms to selectively move material between two environments without altering the unique compositions of those environments. In this review, we summarize our knowledge of the different cell types using transcytosis in vivo, the variety of cargo moved, and the diverse pathways for delivering that cargo. We evaluate in vitro models that are currently being used to study transcytosis. Caveolae-mediated transcytosis by endothelial cells that line the microvasculature and carry circulating plasma proteins to the interstitium is explained in more detail, as is clathrin-mediated transcytosis of IgA by epithelial cells of the digestive tract. The molecular basis of vesicle traffic is discussed, with emphasis on the gaps and uncertainties in our understanding of the molecules and mechanisms that regulate transcytosis. In our view there is still much to be learned about this fundamental process.


RSC Advances ◽  
2017 ◽  
Vol 7 (22) ◽  
pp. 13104-13111 ◽  
Author(s):  
Natália Vilaça ◽  
Ana F. Machado ◽  
Filipa Morais-Santos ◽  
Ricardo Amorim ◽  
A. Patrícia Neto ◽  
...  

5-FU release profiles reveled to be dependent on the host structures. 5-FU DDS led to significant potentiation of the 5-FU effect in cancer cells.


Author(s):  
Thomas W. Gilbert ◽  
James H.-C. Wang ◽  
Stephen F. Badylak ◽  
Savio L.-Y. Woo

In an effort to better understand the role of mechanical loading on the healing and remodeling of biological tissues, a number of in vitro models have been developed to apply either static or cyclic mechanical load to cell-seeded scaffolds (Huang 1993, Langelier 1999, Cacou 2000). The current study describes the validation of a new system designed to facilitate the study of matrix remodeling in cell seeded scaffolds, as well as the formation of tissue engineered scaffolds for potential use in repair of healing ligaments and tendons. Our objective was to develop a system that would allow a cell seeded scaffold to remain viable under cyclic loading for long periods of time, with the capability to apply complex loading regimes to the scaffold while monitoring the load in the scaffold.


Nanomaterials ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 884 ◽  
Author(s):  
Simona Sapino ◽  
Daniela Chirio ◽  
Elena Peira ◽  
Elena Abellán Rubio ◽  
Valentina Brunella ◽  
...  

The bioavailability of ophthalmic therapeutics is reduced because of the presence of physiological barriers whose primary function is to hinder the entry of exogenous agents, therefore also decreasing the bioavailability of locally administered drugs. Consequently, repeated ocular administrations are required. Hence, the development of drug delivery systems that ensure suitable drug concentration for prolonged times in different ocular tissues is certainly of great importance. This objective can be partially achieved using thermosensitive drug delivery systems that, owing to their ability of changing their state in response to temperature variations, from room to body temperature, may increase drug bioavailability. In the case of topical instillation, in situ forming gels increase pre-corneal drug residence time as a consequence of their enhanced adhesion to the corneal surface. Otherwise, in the case of intraocular and periocular, i.e., subconjunctival, retrobulbar, peribulbar administration, among others, they have the undoubted advantage of being easily injectable and, owing to their sudden thickening at body temperature, have the ability to form an in situ drug reservoir. As a result, the frequency of administration can be reduced, also favoring the patient’s adhesion to therapy. In the main section of this review, we discuss some of the most common treatment options for ocular diseases, with a special focus on posterior segment treatments, and summarize the most recent improvement deriving from thermosensitive drug delivery strategies. Aside from this, an additional section describes the most widespread in vitro models employed to evaluate the functionality of novel ophthalmic drug delivery systems.


Author(s):  
Isabel Maria Oliveira ◽  
Diogo Castro Fernandes ◽  
Ibrahim Fatih Cengiz ◽  
Rui Luís Reis ◽  
Joaquim Miguel Oliveira

AbstractRheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disorder that mostly affects the synovial joints and can promote both cartilage and bone tissue destruction. Several conservative treatments are available to relieve pain and control the inflammation; however, traditional drugs administration are not fully effective and present severe undesired side effects. Hydrogels are a very attractive platform as a drug delivery system to guarantee these handicaps are reduced, and the therapeutic effect from the drugs is maximized. Furthermore, hydrogels can mimic the physiological microenvironment and have the mechanical behavior needed for use as cartilage in vitro model. The testing of these advanced delivery systems is still bound to animal disease models that have shown low predictability. Alternatively, hydrogel-based human dynamic in vitro systems can be used to model diseases, bypassing some of the animal testing problems. RA dynamic disease models are still in an embryonary stage since advances regarding healthy and inflamed cartilage models are currently giving the first steps regarding complexity increase. Herein, recent studies using hydrogels in the treatment of RA, featuring different hydrogel formulations are discussed. Besides, their use as artificial extracellular matrices in dynamic in vitro articular cartilage is also reviewed.


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