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Editorial

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3 pages, 158 KiB

Open AccessEditorial

Special Issue: Application of Extracellular Matrix in Regenerative Medicine

by Neill J. Turner

Appl. Sci. 2021, 11(7), 3262; https://doi.org/10.3390/app11073262 - 6 Apr 2021

Cited by 6 | Viewed by 1780

Abstract

The present Special Issue comprises a collection of articles addressing the many ways in which extracellular matrix (ECM), or its components parts, can be used in regenerative medicine applications. ECM is a dynamic structure, composed of a three-dimensional architecture of fibrous proteins, proteoglycans, [...] Read more.

The present Special Issue comprises a collection of articles addressing the many ways in which extracellular matrix (ECM), or its components parts, can be used in regenerative medicine applications. ECM is a dynamic structure, composed of a three-dimensional architecture of fibrous proteins, proteoglycans, and glycosaminoglycans, synthesized by the resident cells. Consequently, ECM can be considered as nature’s ideal biologic scaffold material. The articles in this Special Issue cover a range of topics from the use of ECM components to manufacture scaffold materials, understanding how changes in ECM composition can lead to the development of disease, and how decellularization techniques can be used to develop tissue-derived ECM scaffolds for whole organ regeneration and wound repair. This editorial briefly summarizes the most interesting aspects of these articles. Full article

(This article belongs to the Special Issue Application of Extracellular Matrix in Regenerative Medicine)

Research

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21 pages, 2185 KiB

Open AccessFeature PaperArticle

The Antimicrobial Effectiveness and Cytotoxicity of the Antibiotic-Loaded Chitosan: ECM Scaffolds

by Shayla Goller and Neill J. Turner

Appl. Sci. 2020, 10(10), 3446; https://doi.org/10.3390/app10103446 - 16 May 2020

Cited by 13 | Viewed by 3290

Abstract

Background: The development of multifunctional wound dressings with the ability to control hemostasis, limit infection and promote rapid wound healing and constructive tissue remodeling has been a challenge for many years. In view of these challenges, a hybrid scaffold platform was developed that [...] Read more.

Background: The development of multifunctional wound dressings with the ability to control hemostasis, limit infection and promote rapid wound healing and constructive tissue remodeling has been a challenge for many years. In view of these challenges, a hybrid scaffold platform was developed that combined two different extracellular matrices (ECM): ECM from decellularized mammalian tissue and ECM (chitosan) from crustaceans. Both types of ECM have well established clinical benefits that support and promote wound healing and control hemostasis. This scaffold platform could also be augmented with antibiotics to provide bactericidal activity directly to the wound site. Methods: Four different scaffold formulations were developed containing chitosan supplemented with either 20% or 50% urinary bladder matrix (UBM) hydrogel or 1% (w/v) or 10% (w/v) UBM–ECM particulates. 100% chitosan scaffolds were used as controls. The scaffolds were augmented with either minocycline or rifampicin. Escherichia Coli and Staphylococcus Aureus were used to assesses antimicrobial efficacy and duration of activity, while neutral red uptake assays were performed to establish direct and indirect cytotoxicity. Results: Results showed that scaffold handling properties, scaffold integrity over time and the efficacy and release rate of loaded antibiotics could be modified by altering scaffold composition. Moreover, antibiotics were easily released from the scaffold and could remain effective for up to 24 h by modifying the scaffold composition. Variable results with cytotoxicity testing show that further work is required to optimize the scaffold formulations but these proof of principle experiments suggest that these scaffolds have potential as bioactive wound dressings. Full article

(This article belongs to the Special Issue Application of Extracellular Matrix in Regenerative Medicine)

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16 pages, 14154 KiB

Open AccessArticle

Acoustic Fabrication of Collagen–Fibronectin Composite Gels Accelerates Microtissue Formation

by Emma G. Norris, Diane Dalecki and Denise C. Hocking

Appl. Sci. 2020, 10(8), 2907; https://doi.org/10.3390/app10082907 - 23 Apr 2020

Cited by 4 | Viewed by 3259

Abstract

Ultrasound can influence biological systems through several distinct acoustic mechanisms that can be manipulated by varying reaction conditions and acoustic exposure parameters. We recently reported a new ultrasound-based fabrication technology that exploits the ability of ultrasound to generate localized mechanical forces and thermal [...] Read more.

Ultrasound can influence biological systems through several distinct acoustic mechanisms that can be manipulated by varying reaction conditions and acoustic exposure parameters. We recently reported a new ultrasound-based fabrication technology that exploits the ability of ultrasound to generate localized mechanical forces and thermal effects to control collagen fiber microstructure non-invasively. Exposing solutions of type I collagen to ultrasound during the period of microfibril assembly produced changes in collagen fiber structure and alignment, and increased the biological activity of the resultant collagen hydrogels. In the extracellular matrix, interactions between fibronectin and collagen fibrils influence the biological activity of both proteins. Thus, in the present study, we examined how addition of fibronectin to collagen solutions prior to ultrasound exposure affects protein organization and the biological activity of the composite hydrogels. Results indicate that ultrasound can alter the distribution of fibronectin within 3D hydrogels via thermal and non-thermal mechanisms to produce composite hydrogels that support accelerated microtissue formation. The use of acoustic energy to drive changes in protein conformation to functionalize biomaterials has much potential as a unique, non-invasive technology for tissue engineering and regenerative medicine. Full article

(This article belongs to the Special Issue Application of Extracellular Matrix in Regenerative Medicine)

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11 pages, 2155 KiB

Open AccessArticle

Genipin Attachment of Conjugated Gold Nanoparticles to a Decellularized Tissue Scaffold

by Mitch Bellrichard, Colten Snider, Cornelia Dittmar, John Brockman, Dave Grant and Sheila A. Grant

Appl. Sci. 2019, 9(23), 5231; https://doi.org/10.3390/app9235231 - 1 Dec 2019

Cited by 1 | Viewed by 2776

Abstract

Decellularized allograft tissue is used for a wide array of tissue injuries and repair with tenons and ligament repair being among the most common. However, despite their frequent use there is concern over the lengthy inflammatory period and slow healing associated with allografts. [...] Read more.

Decellularized allograft tissue is used for a wide array of tissue injuries and repair with tenons and ligament repair being among the most common. However, despite their frequent use there is concern over the lengthy inflammatory period and slow healing associated with allografts. One promising solution has been the use of nanoparticles. There is currently no easy, fast method to achieve consistent conjugation of nanoparticles to tissue. The available conjugation methods can be time-consuming and/or may create numerous cytotoxic byproducts. Genipin, a naturally derived crosslinking agent isolated from the fruits of Gardenia jasminoides was investigated as a conjugation agent to achieve fast, consistent crosslinking without cytotoxic byproducts. The rational of utilizing genipin is that is reacts spontaneously with amino-group-containing compounds such as proteins, collagens, and gelatins, and does not require extensive washing after conjugation. Porcine diaphragm tendons were decellularized and then immersed in cysteamine functionalized gold nanoparticles and genipin for various time points. Tissue scaffolds were tested for the degree of crosslinking, gold nanoparticle concentrations, and fibroblast attachment and biocompatibility. Results demonstrated that genipin can successfully and reproducibly attach gold nanoparticles to tissue in as little as 15 min. The genipin had no cytotoxic effects and improved fibroblast attachment and proliferation. Genipin can be used to attach gold nanoparticles to tissue in a fast, cell safe manner. Full article

(This article belongs to the Special Issue Application of Extracellular Matrix in Regenerative Medicine)

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Review

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42 pages, 2298 KiB

Open AccessReview

Whole Organ Engineering: Approaches, Challenges, and Future Directions

by Sogu Sohn, Maxwell Van Buskirk, Michael J. Buckenmeyer, Ricardo Londono and Denver Faulk

Appl. Sci. 2020, 10(12), 4277; https://doi.org/10.3390/app10124277 - 22 Jun 2020

Cited by 26 | Viewed by 12744

Abstract

End-stage organ failure remains a leading cause of morbidity and mortality across the globe. The only curative treatment option currently available for patients diagnosed with end-stage organ failure is organ transplantation. However, due to a critical shortage of organs, only a fraction of [...] Read more.

End-stage organ failure remains a leading cause of morbidity and mortality across the globe. The only curative treatment option currently available for patients diagnosed with end-stage organ failure is organ transplantation. However, due to a critical shortage of organs, only a fraction of these patients are able to receive a viable organ transplantation. Those patients fortunate enough to receive a transplant must then be subjected to a lifelong regimen of immunosuppressant drugs. The concept of whole organ engineering offers a promising alternative to organ transplantation that overcomes these limitations. Organ engineering is a discipline that merges developmental biology, anatomy, physiology, and cellular interactions with enabling technologies such as advanced biomaterials and biofabrication to create bioartificial organs that recapitulate native organs in vivo. There have been numerous developments in bioengineering of whole organs over the past two decades. Key technological advancements include (1) methods of whole organ decellularization and recellularization, (2) three-dimensional bioprinting, (3) advanced stem cell technologies, and (4) the ability to genetically modify tissues and cells. These advancements give hope that organ engineering will become a commercial reality in the next decade. In this review article, we describe the foundational principles of whole organ engineering, discuss key technological advances, and provide an overview of current limitations and future directions. Full article

(This article belongs to the Special Issue Application of Extracellular Matrix in Regenerative Medicine)

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40 pages, 13722 KiB

Open AccessReview

Imaging the Extracellular Matrix in Prevalent Cardiovascular Diseases

by Nadia Chaher, Reza Hajhosseiny, Alkystis Phinikaridou and René M. Botnar

Appl. Sci. 2020, 10(11), 4001; https://doi.org/10.3390/app10114001 - 9 Jun 2020

Cited by 6 | Viewed by 4718

Abstract

The extracellular matrix (ECM) is a highly complex macromolecular network present in all tissues and organs. The ECM is continuously remodelling under an orchestrated process facilitated by many matrix-degrading and matrix-synthesising enzymes in both health and disease. Disturbance of this balance can be [...] Read more.

The extracellular matrix (ECM) is a highly complex macromolecular network present in all tissues and organs. The ECM is continuously remodelling under an orchestrated process facilitated by many matrix-degrading and matrix-synthesising enzymes in both health and disease. Disturbance of this balance can be the result of or can lead to various diseases. In cardiovascular diseases (CVDs), changes to the ECM are evident in conditions including: atherosclerosis, myocardial infarction (MI), venous thromboembolism (VTE) and abdominal aortic aneurysm (AAA). ECM proteins and ECM regulating enzymes are differently expressed in various CVDs. Most importantly, the altered deposition, macromolecule arrangement and activity of the ECM makes it an attractive marker of disease onset, pathogenesis and progression. Many medical imaging modalities allow disease assessment by exploiting native image contrast, by using non-targeted or by using protein or cell specific (targeted) imaging probes. However, the ability to directly visualise and quantify changes in specific ECM proteins enhances our understanding of the biological role of these proteins, enables monitoring of disease progression and response to treatment and may improve patient diagnosis and allocation of personalised therapies. This review focuses on the biochemistry of the major extracellular matrix proteins and advancements in the development of ECM-targeted probes for molecular imaging of CVD, particularly for applications of molecular magnetic resonance imaging (MRI) and position emission tomography (PET) imaging. Full article

(This article belongs to the Special Issue Application of Extracellular Matrix in Regenerative Medicine)

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24 pages, 1623 KiB

Open AccessFeature PaperReview

Decellularized Scaffolds for Skin Repair and Regeneration

by Mélissa Dussoyer, Anna Michopoulou and Patricia Rousselle

Appl. Sci. 2020, 10(10), 3435; https://doi.org/10.3390/app10103435 - 15 May 2020

Cited by 58 | Viewed by 11244

Abstract

The skin is the largest organ in the body, fulfilling a variety of functions and acting as a barrier for internal organs against external insults. As for extensive or irreversible damage, skin autografts are often considered the gold standard, however inherent limitations highlight [...] Read more.

The skin is the largest organ in the body, fulfilling a variety of functions and acting as a barrier for internal organs against external insults. As for extensive or irreversible damage, skin autografts are often considered the gold standard, however inherent limitations highlight the need for alternative strategies. Engineering of human-compatible tissues is an interdisciplinary and active field of research, leading to the production of scaffolds and skin substitutes to guide repair and regeneration. However, faithful reproduction of extracellular matrix (ECM) architecture and bioactive content capable of cell-instructive and cell-responsive properties remains challenging. ECM is a heterogeneous, connective network composed of collagens, glycoproteins, proteoglycans, and small molecules. It is highly coordinated to provide the physical scaffolding, mechanical stability, and biochemical cues necessary for tissue morphogenesis and homeostasis. Decellularization processes have made it possible to isolate the ECM in its native and three-dimensional form from a cell-populated tissue for use in skin regeneration. In this review, we present recent knowledge about these decellularized biomaterials with the potential to be used as dermal or skin substitutes in clinical applications. We detail tissue sources and clinical indications with success rates and report the most effective decellularization methods compatible with clinical use. Full article

(This article belongs to the Special Issue Application of Extracellular Matrix in Regenerative Medicine)

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9 pages, 1119 KiB

Open AccessReview

Secreted Protein Acidic and Rich in Cysteine: Metabolic and Homeostatic Properties beyond the Extracellular Matrix Structure

by Abdelaziz Ghanemi, Mayumi Yoshioka and Jonny St-Amand

Appl. Sci. 2020, 10(7), 2388; https://doi.org/10.3390/app10072388 - 1 Apr 2020

Cited by 19 | Viewed by 3812

Abstract

An extracellular matrix (ECM) is a network of numerous macromolecules that represents the cellular structural support involved in key biofunctions such as signal transduction and cellular adhesion. In addition, ECM-associated proteins interact with ECM and with other endogenous structures and molecules to control [...] Read more.

An extracellular matrix (ECM) is a network of numerous macromolecules that represents the cellular structural support involved in key biofunctions such as signal transduction and cellular adhesion. In addition, ECM-associated proteins interact with ECM and with other endogenous structures and molecules to control cellular growth, structural modifications, cellular migration, etc. Among the ECM-associated proteins, secreted protein acidic and rich in cysteine (SPARC) is a protein that is known to be expressed when tissues change. Herein, we put a spotlight on selected, metabolic and homeostatic properties beyond the known properties of ECM and SPARC. Importantly, the synchronization of the metabolic and structural implications of SPARC and the ECM would indicate an adaptation of the metabolism to meet the needs of the changes that the tissues undergo. Highlighting such properties would have important applications in diverse fields that include therapeutics, metabolics, and pathogenesis. Full article

(This article belongs to the Special Issue Application of Extracellular Matrix in Regenerative Medicine)

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