Alireza Shahin‐Shamsabadi

Evolved Analytics (United States)

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P. Ravi Selvaganapathy

McMaster University

John Cappuccitti

Evolved Analytics (United States)

Mohammadreza Tahriri

Marquette University

Farshid Bastami

University of Tehran

Kathryn Grandfield

McMaster University

Michael K. Wong

The University of Texas MD Anderson Cancer Center

Bryan Lee

University of Nevada, Reno

Sandeep Raha

McMaster University

Fatemeh Mashhadi Abbas

Shahid Beheshti University of Medical Sciences

Ata Hashemi

Amirkabir University of Technology

Cooperative Institutions

McMaster University

Nuremberg Hospital

University of Toronto

Hamilton Health Sciences

McMaster Children's Hospital

Amirkabir University of Technology

McMaster University Medical Centre

Shahed University

University of Tehran

Shahid Beheshti University of Medical Sciences

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A Viscoelastic Study of Poly(ε-Caprolactone) Microsphere Sintered Bone Tissue Engineering Scaffold

Journal of Medical and Biological Engineering (2017)

Alireza Shahin‐Shamsabadi Ata Hashemi Mohammadreza Tahriri

Caprolactone

Bone tissue

Stress relaxation

Cancellous bone

10.1007/s40846-017-0325-2

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Citations (5)

A Rapid Fabrication Technique for Self-Assembled Collagen Based Multicellular, Heterogeneous, 3D Tissue Constructs

SSRN Electronic Journal (2019)

Alireza Shahin‐Shamsabadi P. Ravi Selvaganapathy

Although monolayer cell culture models are considered to be the gold standard for in vitro modeling of pathophysiological events, they cannot reconstruct in vivo like gradient of gases and nutrients and lack proper cell-cell and cell-matrix interactions. Spherical cellular aggregates, otherwise known as multicellular spheroids, are widely used as three-dimensional in vitro models to mimic natural in vivo cellular microenvironment for applications such as drug screening. Although very useful, the previously established techniques are limited to low cell numbers, usually slow, and sometimes have limitations in terms of the cell type that can be used. Here, a versatile technique based on rapid self-assembly of cells and extracellular matrix materials and shapes using microfabricated molds is introduced to form multicellular tissue constructs. The self-assembly process takes less than 6 hrs and produces a mechanically robust tissue construct that could be handled easily. We demonstrate that a variety of shapes including spherical, cuboidal, dumbbell- and cross-like could be fabricated using this approach. Interestingly, the structures formed with non-spherical shapes were able to retain that shape even after removal from the molds and during long term cell culture. This versatile approach is applicable to a variety of cell types (breast cancer cell lines MCF-7, MDA-MB-321, Hs-578T; osteosarcoma cell line SaOS-2; endothelial cell line HUVEC) as well as a range of cell numbers (104-106). Furthermore, we also show that the constructs could be spatially patterned to position various cell types in a precisely controlled way. Such heterogeneous constructs that are formed provide physiologically relevant cell densities, 3D structure as well as close positioning of multiple types of cells that are not possible using other fabrication approaches. This fabrication approach will find significant applications in developing 3D cell culture models for drug discovery as well as tissue grafts for implantation.

Multicellular organism

10.2139/ssrn.3330021

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Poly(lactic-co-glycolic acid)(PLGA)/TiO 2 nanotube bioactive composite as a novel scaffold for bone tissue engineering: In vitro and in vivo studies

Biologicals (2018)

Hossein Eslami Hamidreza Azimi Lisar Tahereh Sadat Jafarzadeh Kashi Mohammadreza Tahriri Mojtaba Ansari

PLGA

Glycolic acid

10.1016/j.biologicals.2018.02.004

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Citations (60)

A Pumpless Microfluidic Neonatal Lung Assist Device for Support of Preterm Neonates in Respiratory Distress

Advanced Science (2020)

Mohammadhossein Dabaghi Niels Rochow Neda Saraei Gerhard Fusch Shelley Monkman

Abstract Premature neonates suffer from respiratory morbidity as their lungs are immature, and current supportive treatment such as mechanical ventilation or extracorporeal membrane oxygenation causes iatrogenic injuries. A non‐invasive and biomimetic concept known as the “artificial placenta” (AP) would be beneficial to overcome complications associated with the current respiratory support of preterm infants. Here, a pumpless oxygenator connected to the systemic circulation supports the lung function to relieve respiratory distress. In this paper, the first successful operation of a microfluidic, artificial placenta type neonatal lung assist device (LAD) on a newborn piglet model, which is the closest representation of preterm human infants, is demonstrated. This LAD has high oxygenation capability in both pure oxygen and room air as the sweep gas. The respiratory distress that the newborn piglet is put under during experimentation, repeatedly and over a significant duration of time, is able to be relieved. These findings indicate that this LAD has a potential application as a biomimetic artificial placenta to support the respiratory needs of preterm neonates.

Oxygenator

Artificial lung

10.1002/advs.202001860

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Citations (24)

In Vivo‐Like Scaffold‐Free 3D In Vitro Models of Muscular Dystrophies: The Case for Anchored Cell Sheet Engineering in Personalized Medicine

Advanced Healthcare Materials (2024)

Alireza Shahin‐Shamsabadi John Cappuccitti

Abstract Progress in understanding the underlying mechanisms of muscular dystrophies is hindered by the lack of pathophysiologically relevant in vitro models. Here, an entirely scaffold‐free anchored cell sheet engineering platform is used to create patient‐specific three‐dimensional (3D) skeletal muscle in vitro models. This approach effectively replicates mature muscle phenotypes and tissue‐ and disease‐specific extracellular matric (ECM). Models were developed using primary cells from healthy individuals and patients with Duchenne Muscular Dystrophy and Myotonic Dystrophy Type 1. Through a combination of quantified histological staining (Hematoxylin & Eosin, Movat's Pentachrome, Masson's Trichrome) and immunostaining (desmin, myosin heavy chain, laminin, and dystrophin), it was demonstrated that the models formed mature constructs closely resembling their respective in vivo conditions. Proteomics analysis revealed that the models exhibited appropriate upregulation and downregulation of disease‐relevant pathways. Models of diseased tissues accurately reflected key phenotypic features of the diseases, including alterations in muscle fiber integrity and ECM composition. Upon treatment with therapeutically beneficial drugs, significant changes in their proteomic profiles were documented, highlighting the models’ potential for drug screening. This novel in vitro modeling approach, unlike other 3D techniques that rely on exogenous biomaterials that interfere with natural cellular behaviors, provides a promising platform for studying muscular dystrophies.

Desmin

Utrophin

10.1002/adhm.202404465

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Mechanical, material, and biological study of a PCL/bioactive glass bone scaffold: Importance of viscoelasticity

Materials Science and Engineering C (2018)

Alireza Shahin‐Shamsabadi Ata Hashemi Mohammadreza Tahriri Farshid Bastami Majid Salehi

Polycaprolactone

Bioactive Glass

ALIZARIN RED

Bone tissue

10.1016/j.msec.2018.04.080

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Citations (59)

Anchored Cell Sheet Engineering: A Novel Scaffold‐Free Platform for in vitro Modeling

Advanced Functional Materials (2023)

Alireza Shahin‐Shamsabadi John Cappuccitti

Abstract Biofabricated in vitro models hold unrealized potential in accelerating drug discovery and reducing new drug costs, but current models are overly simplified and lack physiological relevance. Certain platforms capable of mimicking in vivo conditions face hurdles such as complexity, high costs, and non‐standardized applications. Existing cell sheet engineering methodologies, despite being physiologically relevant, have technical limitations like creating suitable 3D forms with proper anchorage. An innovative platform is introduced here, designed for in vitro modeling, which capitalizes on 2D culture systems and scaffold‐free cell sheets to create self‐assembling 3D tissue constructs. It provides precise control over cellular behavior, especially ECM production and remodeling. Scaffold‐free muscle fibers and lung epithelial cell cultures served as examples. This platform can fuse various scaffold‐free models to construct assembloids mimicking organ structures and functions. Different tissues can be linked via a fluidic system for body‐level simulations. Moreover, ECM‐rich constructs from cell sheets can create organ‐level ECM scaffolds, and the resulting cell sheet‐derived ECM (CSdECM) can be solubilized to facilitate 2D cellular behavior. This versatile platform, compatible with other cell sheet engineering techniques, is set to revolutionize in vitro modeling.

3D cell culture

10.1002/adfm.202308552

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Citations (8)

Anchored Cell Sheet Engineering: A Novel Scaffold‐Free Platform for in vitro Modeling (Adv. Funct. Mater. 13/2024)

Advanced Functional Materials (2024)

Alireza Shahin‐Shamsabadi John Cappuccitti

10.1002/adfm.202470071

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Citations (0)

A 3D Self‐Assembled In Vitro Model to Simulate Direct and Indirect Interactions between Adipocytes and Skeletal Muscle Cells

Advanced Biosystems (2020)

Alireza Shahin‐Shamsabadi P. Ravi Selvaganapathy

Abstract The molecular mechanisms of the development and progression of diabetes and obesity involve complex interactions between adipocytes and skeletal muscle cells. Although 2D in‐vitro models are the gold standard for the mechanistic study of such behaviors, they do not recreate the complexity and dynamics of the interactions between the cell types involved. Alternatively, animal models are used but are expensive, difficult to visualize or analyze, are not completely representative of human physiology or genetic background, and have associated ethical considerations. 3D co‐culture systems can be complementary to these approaches. Here, using a newly developed 3D biofabrication method, adipocytes and myoblasts are positioned precisely either in direct physical contact or in close proximity such that the paracrine effects could be systematically studied. Suitable protocols for growth and differentiation of both cells in the co‐culture system is also developed. Cells show more restrained lipid and protein production in 3D systems compared to 2D ones and adipocytes show more lipolysis in indirect contact with myoblasts as response to drug treatment. These findings emphasize importance of physical contact between cells that have been overlooked in co‐culture systems using transwell inserts and can be used in studies for the development of anti‐obesity drugs.

Biofabrication

10.1002/adbi.202000034

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Citations (17)

Engineering Murine Adipocytes and Skeletal Muscle Cells in Meat-like Constructs Using Self-Assembled Layer-by-Layer Biofabrication: A Platform for Development of Cultivated Meat

Cells Tissues Organs (2021)

Alireza Shahin‐Shamsabadi P. Ravi Selvaganapathy

Global meat consumption has been growing on a per capita basis over the past 20 years resulting in ever-increasing devotion of resources in the form of arable land and potable water to animal husbandry which is unsustainable and inefficient. One approach to meet this insatiable demand is to use biofabrication methods used in tissue engineering in order to make skeletal muscle tissue-like constructs known as cultivated meat to be used as a food source. Here, we demonstrate the use of a scaffold-free biofabrication method that forms cell sheets composed of murine adipocytes and skeletal muscle cells and assembles these sheets in parallel to create a 3D meat-like construct without the use of any exogenous materials. This layer-by-layer self-assembly and stacking process is fast (4 days of culture to form sheets and few hours for assembly) and scalable (stable sheets with diameters >3 cm are formed). Tissues formed with only muscle cells were equivalent to lean meat with comparable protein and fat contents (lean beef had 1.5 and 0.9 times protein and fat, respectively, as our constructs) and incorporating adipocyte cells in different ratios to myoblasts and/or treatment with different media cocktails resulted in a 5% (low fat meat) to 35% (high fat meat) increase in the fat content. Not only such constructs can be used as cultivated meat, they can also be used as skeletal muscle models.

Biofabrication

10.1159/000511764

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Citations (30)