Milica Radisic’s research while affiliated with University of Toronto and other places

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Publications (29)


Primitive macrophages enable long-term vascularization of human heart-on-a-chip platforms
  • Article

June 2024

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56 Reads

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24 Citations

Cell Stem Cell

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Homaira Hamidzada

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Milica Radisic

Beyond Polydimethylsiloxane: Alternative Materials for Fabrication of Organ-on-a-Chip Devices and Microphysiological Systems

August 2020

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1,933 Reads

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218 Citations

ACS Biomaterials Science & Engineering

Polydimethylsiloxane (PDMS) is the predominant material used for organ-on-a-chip devices and microphysiological systems (MPSs) due to its ease-of-use, elasticity, optical transparency, and inexpensive microfabrication. However, the absorption of small hydrophobic molecules by PDMS and the limited capacity for high-throughput manufacturing of PDMS-laden devices severely limit the application of these systems in personalized medicine, drug discovery, in vitro pharmacokinetic/pharmacodynamic (PK/PD) modelling, and the investigation of cellular responses to drugs. Consequently, the relatively young field of organ-on-a-chip devices and MPSs is gradually beginning to make the transition to alternative, non-absorptive materials for these crucial applications. This review examines some of the first steps that have been made in the development of organ-on-a-chip devices and MPSs composed of such alternative materials, including elastomers, hydrogels, thermoplastic polymers, and inorganic materials. It also provides an outlook on where PDMS-alternative devices are trending and the obstacles that must be overcome in the development of versatile devices based on alternative materials to PDMS.



Special Issue on Tissue Engineering
  • Article
  • Full-text available

September 2017

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59 Reads

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8 Citations

ACS Biomaterials Science & Engineering

Download



FIG. 1. Various biochemical and biophysical cues provided by matrix to regulate the native cell response. Growth factors and derivatives can interact with native cells through their specific receptors. The composition of ECM proteins is usually recognized by integrins. Small bioactive molecules, including oxygen and NO, can diffuse into the cells and mainly affect mitochondrial activities. Genetic regulators, including cDNA, miRNA, and siRNA, can be delivered by nonviral vehicles and facilitate gene transcription and translation. Electric or magnetic cues can also influence cell responses such as migration. cDNA, complementary DNA; ECM, extracellular matrix; miRNA, microRNA; NO, nitric oxide; siRNA, small interfering RNA. Color images available online at www.liebertpub.com/teb
Table 1 . Commercially Available Matrices and Devices for Diabetic Ulcer Treatment
FIG. 2. Engineered biomaterials using topographical guidance. (a) Schematic of wound treatment using a microgrooved PDMS patch. (b) Porous polymer matrix fabricated by sphere templating. (c) Electrospun fibers aligned in radial orientation. (d) Microisland arrays of electrospun nanofibers. Reproduced with the permission from Refs. 170,177,222,223 Copyrights 2012 Royal Society of Chemistry, 2012 John Wiley and Sons, 2010 American Chemical Society, and 2010 John Wiley and Sons, respectively. PDMS, polydimethylsiloxane. Color images available online at www.liebertpub.com/teb
Table 2 . Research Strategies to Improve Diabetic Wound Healing
FIG. 4. Schematic diagram of design, application (a), and electric fields (b) generated by Procellera Ò bioelectric dressing. Courtesy of Banerjee et al. 203 Color images available online at www.liebertpub.com/teb  

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Biochemical and Biophysical Cues in Matrix Design for Chronic and Diabetic Wound Treatment

July 2016

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840 Reads

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36 Citations

Tissue Engineering Part B Reviews

Progress in biomaterials science and engineering and increasing knowledge in cell biology have enabled us to develop functional biomaterials providing appropriate biochemical and biophysical cues for tissue regeneration applications. Tissue regeneration is particularly important to treat chronic wounds of people with diabetes. Understanding and controlling the cellular microenvironment of the wound tissue are important to improve the wound healing process. Here, we review different biochemical (e.g., growth factors, peptides, DNA, and RNA) and biophysical (e.g., topographical guidance, pressure, electrical stimulation, and pulsed electromagnetic field) cues providing a functional and instructive acellular matrix to heal diabetic chronic wounds. The biochemical and biophysical signals generally regulate cell-matrix interactions, cell behavior and function inducing the tissue regeneration for chronic wounds. Some technologies and devices have already been developed and used in the clinic employing biochemical and biophysical cues for wound healing applications. These technologies can be integrated with smart biomaterials to deliver therapeutic agents to the wound tissue in a precise and controllable manner. This review provides useful guidance in understanding molecular mechanisms and signals in the healing of diabetic chronic wounds and in designing instructive biomaterials to treat them.


Fig. 1. Microtissue platforms: Achieving complexity on a small scale 
Distilling complexity to advance cardiac tissue engineering

June 2016

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195 Reads

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159 Citations

Science Translational Medicine

The promise of cardiac tissue engineering is in the ability to recapitulate in vitro the functional aspects of a healthy heart and disease pathology as well as to design replacement muscle for clinical therapy. Parts of this promise have been realized; others have not. In a meeting of scientists in this field, five central challenges or "big questions" were articulated that, if addressed, could substantially advance the current state of the art in modeling heart disease and realizing heart repair.


Tissue engineering: Signals from within

May 2016

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28 Reads

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5 Citations

Nature Materials

A regenerative cardiac patch with integrated freestanding electrodes allows the electrical stimulation and recording of cardiomyocyte growth and activity, with on-demand drug delivery.


Strategies and Challenges to Myocardial Replacement Therapy

March 2016

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43 Reads

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40 Citations

STEM CELLS TRANSLATIONAL MEDICINE

Significance: This article outlines the advantages and limitations of the cell injection and patch approaches to cardiac regenerative therapy. If the field is to move forward, some fundamental questions require answers, including the limitations to the use of animal models for human cell-transplantation studies; the best way to measure success in terms of functional improvements, histological integration, electrical coupling, and arrhythmias; and where the cells should be applied for maximal benefit-the epicardium or the myocardium.


Citations (22)


... Recent studies have also demonstrated the potential of macrophages to address the dearth of vascularization observed in cardiac organoids. Landau et al. incorporated hiPSC-derived macrophages into heart-on-achip, observing the formation of stable and perfusable microvasculature within cardiac tissue [118]. RNA-seq analysis revealed an upregulation of pro-angiogenic and cardiac maturation markers. ...

Reference:

Engineering Cardiology with Miniature Hearts
Primitive macrophages enable long-term vascularization of human heart-on-a-chip platforms
  • Citing Article
  • June 2024

Cell Stem Cell

... In recent years, biodegradable scaffolds have been widely used in tissue engineering (TE) applications [1][2][3][4]. An ideal TE scaffold is defined as a porous structure, which is biocompatible, bioactive and possesses adequate mechanical and physical properties, convergent to the tissues in place of implantation [5][6][7]. Mimicking the complex architecture and mechanical properties of the native tissue is one of the most important paradigms in tissue engineering. 3D printing can be implemented to fulfill this criterion. ...

Tissue Engineering
  • Citing Chapter
  • January 2017

... These microfluidic devices provide an environment that mimics the mechanical, chemical and physical microenvironments of tissues, surpassing the limitations of static 2D cultures and reducing reliance on animal models 5-7,9 . Many microfluidic devices rely on materials like polydimethylsiloxane (PDMS) 7 , due to its optical clarity, biocompatibility and ease of fabrication [10][11][12][13] . PDMS offers unique properties compared to thermoplastics, such as elasticity and gas permeability. ...

Beyond Polydimethylsiloxane: Alternative Materials for Fabrication of Organ-on-a-Chip Devices and Microphysiological Systems
  • Citing Article
  • August 2020

ACS Biomaterials Science & Engineering

... Polycaprolactone (PCL) is a type of polymer that is highly biodegradable, can be 3D-printed, accepts surface modification well, and shows adaptability and operability [18,19]. However, cells show poor adhesion, proliferation, and differentiation on PCL due to its hydrophobicity and low wettability [20,21]. Research has been conducted to improve the shortcomings of PCL scaffolds by adding various bioactive substances, such as hydroxyapatite and betatricalcium phosphate [22,23]. ...

Special Issue on Tissue Engineering

ACS Biomaterials Science & Engineering

... Today biotechnology is emphasizing the use of genetically modified organisms for bioremediation. 8 The treatment of these pesticides should be done this way that the degradation of the compound will not generate intermediates. The existing technologies are using physical or chemical ways to treat the pesticides, and according to FAO, they could cost up to 3000-4000 USD/tons. ...

Engagement of the medical-Technology sector with society
  • Citing Article
  • April 2017

Science Translational Medicine

... The scaffolds are specifically designed to provide essential structural support while promoting tissue regeneration. By mimicking the natural extracellular matrix, they create an environment that encourages cell growth and repair, ultimately assisting the tissue in recovering its functional capabilities [6][7][8]. ...

Biochemical and Biophysical Cues in Matrix Design for Chronic and Diabetic Wound Treatment

Tissue Engineering Part B Reviews

... On the other hand, research on myocardial tissue engineering using cell sheets [8,9] and cell spheroids [10,11] without extracellular matrix has been conducted. Although remarkable progress has been made in myocardial tissue engineering, rapid construction and transplantation efficiency have not yet been demonstrated [12]. For the purpose of cell therapy, we developed a technique involving lowering the temperature to induce hydrophilicity on the culture dish surface, which allows the cells to be peeled off and collected as a sheet. ...

Distilling complexity to advance cardiac tissue engineering

Science Translational Medicine

... [5b,d] More recently, we have also demonstrated the use of elastomer-bonded standing AuNWs for strain and electrochemical biosensors. [14] On the other hand, fibers are crucial materials with numerous technical applications ranging from textile products, membrane filtration, [15] catalysis, [16] tissue engineering, [17] and flexible electronics. [18] Previously, methods for preparing mesoporous silica fibers include electrospinning, [19] template method [20] and spontaneous growth. ...

Tissue engineering: Signals from within
  • Citing Article
  • May 2016

Nature Materials

... When reviewing methods to introduce new CMs to the heart, two main delivery routes have been accomplished: transplantation via intramyocardial (or intra-scar) injection (as single-cell solution or small aggregates) and the epicardial application of preformed 3Dconstructs ( Figure 3). Both approaches carry their advantages and drawbacks (Feric and Radisic, 2016;Kadota and Shiba, 2019). Although efficacy was repeatedly proven in small animal models for both delivery approaches, the CM injection strategy has been mainly tested in NHP models (Tables 1, 2). ...

Strategies and Challenges to Myocardial Replacement Therapy
  • Citing Article
  • March 2016

STEM CELLS TRANSLATIONAL MEDICINE

... Furthermore, treatment of constructs with a combination of electrical pacing and insulin-like growth factor 1 (IGF-1) supplementation has been shown to further improve the contractile properties and connexin-43 expression in engineered heart constructs over and above levels observed in response to either factor applied independently (Park et al. , 2014). The integration of three-dimensional cardiac biowires (derived from pluripotent stem cell sources) with long-term stimulation protocols for up to 4 weeks in vitro promotes improvements in sarcomeric banding (Figure 3E,F), excitation thresholds, and conduction velocities (Nunes et al. , 2013, Xiao et al. , 2014). Cells from these preparations also exhibit larger hERG currents, more negative resting membrane potentials, and larger capacitances (suggesting larger cells) than unstimulated controls, further indicating the improved functionality of cardiomyocytes exposed to long-term electrical stimulation (Nunes, Miklas, 2013). ...

Microfabricated Perfusable Cardiac Biowire: A Platform That Mimics Native Cardiac Bundle
  • Citing Conference Paper
  • December 2014

Tissue Engineering Part A