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Bioengineering
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Extracellular Matrix in Musculoskeletal Regeneration
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Extracellular Matrix in Musculoskeletal Regeneration

A special issue of Bioengineering (ISSN 2306-5354). This special issue belongs to the section "Regenerative Engineering".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 16731

Special Issue Editors

Dr. Michael J. Mcclure

E-Mail Website
Guest Editor
Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 843068, USA
Interests: skeletal muscle; cell and tissue engineering; biomaterials; extracellular matrix; innervation; rehabilitation; volumetric muscle loss
Special Issues, Collections and Topics in MDPI journals
Dr. Joshua Cohen

E-Mail Website
Guest Editor
Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA
Interests: microCT imaging; orthopedic and dental implantology; breast cancer metastasis to bone; small animal model surgery

Special Issue Information

Dear Colleagues,

The overall focus of this Special Issue is on the influence of the extracellular matrix to regulate musculoskeletal health and regeneration in cases of osteoarthritis, osteopenia, sarcopenia, and other musculoskeletal trauma. The extracellular matrix influences stem cell behavior through its physical structure, available ligands, and source of growth factors. Moreover, the extracellular matrix has the ability to sequester and facilitate specific packaging of extracellular vesicles, making it a potent regulator of stem cell proliferation and differentiation. Recent advances in synthetic and naturally derived biomaterials allow us to study the translational and transformative aspects of the extracellular matrix in musculoskeletal regeneration, especially when attempting to regenerate tissue in austere microenvironments related to disease or trauma.  

This Special Issue on “Extracellular Matrix in Musculoskeletal Regeneration” is open for original papers and reviews investigating extracellular matrix biology in normal, diseased, or injured bone, cartilage, or skeletal muscle. Topics and themes for this collection will include but are not limited to the following:

  • Tissue-specific extracellular matrix scaffolds used to regenerate bone, cartilage, or skeletal muscle;
  • Extracellular matrix-mediated stem cell differentiation in musculoskeletal tissue;
  • Biophysical properties of extracellular matrix and its effect on musculoskeletal stem cells;
  • Extracellular vesicles derived from bone, cartilage, or muscle to drive stem cell fate;
  • Synthetic and natural derived biomimetic extracellular matrix scaffolds used in bone, cartilage, or skeletal muscle regeneration;
  • Influence of bone, cartilage, or skeletal muscle crosstalk signaling on extracellular matrix and regeneration;
  • Microfluidic devices used to identify extracellular matrix-related changes due to tissue crosstalk.

Dr. Michael J. Mcclure
Prof. Joshua Cohen
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Bioengineering is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • extracellular matrix
  • extracellular vesicles
  • exosomes
  • surface modifications
  • biomimetic
  • biomaterials
  • skeletal muscle
  • cartilage
  • bone

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Published Papers (4 papers)

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Research

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11 pages, 2654 KiB  
Article
Decellularised Cartilage ECM Culture Coatings Drive Rapid and Robust Chondrogenic Differentiation of Human Periosteal Cells
by Wollis J. Vas, Mittal Shah, Helen C. Roberts and Scott J. Roberts
Bioengineering 2022, 9(5), 203; https://doi.org/10.3390/bioengineering9050203 - 10 May 2022
Cited by 4 | Viewed by 2951
Abstract
The control of cell behaviour in an effort to create highly homogeneous cultures is becoming an area of intense research, both to elucidate fundamental biology and for regenerative applications. The extracellular matrix (ECM) controls many cellular processes in vivo, and as such is [...] Read more.
The control of cell behaviour in an effort to create highly homogeneous cultures is becoming an area of intense research, both to elucidate fundamental biology and for regenerative applications. The extracellular matrix (ECM) controls many cellular processes in vivo, and as such is a rich source of cues that may be translated in vitro. Herein, we describe the creation of cell culture coatings from porcine decellularised hyaline cartilage through enzymatic digestion. Surprisingly, heat-mediated sterilisation created a coating with the capacity to rapidly and robustly induce chondrogenic differentiation of human periosteal cells. This differentiation was validated through the alteration of cell phenotype from a fibroblastic to a cuboidal/cobblestone chondrocyte-like appearance. Moreover, chondrogenic gene expression further supported this observation, where cells cultured on heat sterilised ECM-coated plastic displayed higher expression of COL2A1, ACAN and PRG4 (p < 0.05) compared to non-coated plastic cultures. Interestingly, COL2A1 and ACAN expression in this context were sensitive to initial cell density; however, SOX9 expression appeared to be mainly driven by the coating independent of seeding density. The creation of a highly chondrogenic coating may provide a cost-effective solution for the differentiation and/or expansion of human chondrocytes aimed towards cartilage repair strategies. Full article
(This article belongs to the Special Issue Extracellular Matrix in Musculoskeletal Regeneration)
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19 pages, 4193 KiB  
Article
Multiscale Characterization of Type I Collagen Fibril Stress–Strain Behavior under Tensile Load: Analytical vs. MD Approaches
by Afif Gouissem, Raouf Mbarki, Fadi Al Khatib and Malek Adouni
Bioengineering 2022, 9(5), 193; https://doi.org/10.3390/bioengineering9050193 - 28 Apr 2022
Cited by 5 | Viewed by 2964
Abstract
Type I collagen is one of the most important proteins in the human body because of its role in providing structural support to the extracellular matrix of the connective tissues. Understanding its mechanical properties was widely investigated using experimental testing as well as [...] Read more.
Type I collagen is one of the most important proteins in the human body because of its role in providing structural support to the extracellular matrix of the connective tissues. Understanding its mechanical properties was widely investigated using experimental testing as well as molecular and finite element simulations. In this work, we present a new approach for defining the properties of the type I collagen fibrils by analytically formulating its response when subjected to a tensile load and investigating the effects of enzymatic crosslinks on the behavioral response. We reveal some of the shortcomings of the molecular dynamics (MD) method and how they affect the obtained stress–strain behavior of the fibril, and we prove that not only does MD underestimate the Young’s modulus and the ultimate tensile strength of the collagen fibrils, but also fails to detect the mechanics of some stretching phases of the fibril. We prove that non-crosslinked fibrils have three tension phases: (i) an initial elastic deformation corresponding to the collagen molecule uncoiling, (ii) a linear regime related to the stretching of the backbone of the tropocollagen molecules, and (iii) a plastic regime dominated by molecular sliding. We also show that for crosslinked fibrils, the second regime can be subdivided into three sub-regimes, and we define the properties of each regime. We also prove, analytically, the alleged MD quadratic relation between the ultimate tensile strength of the fibril and the concentration of enzymatic crosslinks (β). Full article
(This article belongs to the Special Issue Extracellular Matrix in Musculoskeletal Regeneration)
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15 pages, 2784 KiB  
Article
Comparative Effects of Basic Fibroblast Growth Factor Delivery or Voluntary Exercise on Muscle Regeneration after Volumetric Muscle Loss
by Caroline Hu, Bugra Ayan, Gladys Chiang, Alex H. P. Chan, Thomas A. Rando and Ngan F. Huang
Bioengineering 2022, 9(1), 37; https://doi.org/10.3390/bioengineering9010037 - 14 Jan 2022
Cited by 11 | Viewed by 3717
Abstract
Volumetric muscle loss (VML) is associated with irreversibly impaired muscle function due to traumatic injury. Experimental approaches to treat VML include the delivery of basic fibroblast growth factor (bFGF) or rehabilitative exercise. The objective of this study was to compare the effects of [...] Read more.
Volumetric muscle loss (VML) is associated with irreversibly impaired muscle function due to traumatic injury. Experimental approaches to treat VML include the delivery of basic fibroblast growth factor (bFGF) or rehabilitative exercise. The objective of this study was to compare the effects of spatially nanopatterned collagen scaffold implants with either bFGF delivery or in conjunction with voluntary exercise. Aligned nanofibrillar collagen scaffold bundles were adsorbed with bFGF, and the bioactivity of bFGF-laden scaffolds was examined by skeletal myoblast or endothelial cell proliferation. The therapeutic efficacy of scaffold implants with either bFGF release or exercise was examined in a murine VML model. Our results show an initial burst release of bFGF from the scaffolds, followed by a slower release over 21 days. The released bFGF induced myoblast and endothelial cell proliferation in vitro. After 3 weeks of implantation in a mouse VML model, twitch force generation was significantly higher in mice treated with bFGF-laden scaffolds compared to bFGF-laden scaffolds with exercise. However, myofiber density was not significantly improved with bFGF scaffolds or voluntary exercise. In contrast, the scaffold implant with exercise induced more re-innervation than all other groups. These results highlight the differential effects of bFGF and exercise on muscle regeneration. Full article
(This article belongs to the Special Issue Extracellular Matrix in Musculoskeletal Regeneration)
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Review

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14 pages, 1162 KiB  
Review
Advanced Glycation End-Products in Skeletal Muscle Aging
by Lucas C. Olson, James T. Redden, Zvi Schwartz, David J. Cohen and Michael J. McClure
Bioengineering 2021, 8(11), 168; https://doi.org/10.3390/bioengineering8110168 - 1 Nov 2021
Cited by 26 | Viewed by 5764
Abstract
Advanced age causes skeletal muscle to undergo deleterious changes including muscle atrophy, fast-to-slow muscle fiber transition, and an increase in collagenous material that culminates in the age-dependent muscle wasting disease known as sarcopenia. Advanced glycation end-products (AGEs) non-enzymatically accumulate on the muscular collagens [...] Read more.
Advanced age causes skeletal muscle to undergo deleterious changes including muscle atrophy, fast-to-slow muscle fiber transition, and an increase in collagenous material that culminates in the age-dependent muscle wasting disease known as sarcopenia. Advanced glycation end-products (AGEs) non-enzymatically accumulate on the muscular collagens in old age via the Maillard reaction, potentiating the accumulation of intramuscular collagen and stiffening the microenvironment through collagen cross-linking. This review contextualizes known aspects of skeletal muscle extracellular matrix (ECM) aging, especially the role of collagens and AGE cross-linking, and underpins the motor nerve’s role in this aging process. Specific directions for future research are also discussed, with the understudied role of AGEs in skeletal muscle aging highlighted. Despite more than a half century of research, the role that intramuscular collagen aggregation and cross-linking plays in sarcopenia is well accepted yet not well integrated with current knowledge of AGE’s effects on muscle physiology. Furthermore, the possible impact that motor nerve aging has on intramuscular cross-linking and muscular AGE levels is posited. Full article
(This article belongs to the Special Issue Extracellular Matrix in Musculoskeletal Regeneration)
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