Extracellular Matrix-Derived Hydrogels as Biomaterial for Different Skeletal Muscle Tissue Replacements

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Abstract

Recently, skeletal muscle represents a complex and challenging tissue to be generated in vitro for tissue engineering purposes. Several attempts have been pursued to develop hydrogels with different formulations resembling in vitro the characteristics of skeletal muscle tissue in vivo. This review article describes how different types of cell-laden hydrogels recapitulate the multiple interactions occurring between extracellular matrix (ECM) and muscle cells. A special attention is focused on the biochemical cues that affect myocytes morphology, adhesion, proliferation, and phenotype maintenance, underlining the importance of topographical cues exerted on the hydrogels to guide cellular orientation and facilitate myogenic differentiation and maturation. Moreover, we highlight the crucial role of 3D printing and bioreactors as useful platforms to finely control spatial deposition of cells into ECM based hydrogels and provide the skeletal muscle native-like tissue microenvironment, respectively.

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Skeletal muscle: a brief review of structure and function.

Walter R Frontera, Julien Ochala (2015)

Skeletal muscle is one of the most dynamic and plastic tissues of the human body. In humans, skeletal muscle comprises approximately 40% of total body weight and contains 50-75% of all body proteins. In general, muscle mass depends on the balance between protein synthesis and degradation and both processes are sensitive to factors such as nutritional status, hormonal balance, physical activity/exercise, and injury or disease, among others. In this review, we discuss the various domains of muscle structure and function including its cytoskeletal architecture, excitation-contraction coupling, energy metabolism, and force and power generation. We will limit the discussion to human skeletal muscle and emphasize recent scientific literature on single muscle fibers.

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Inflammatory processes in muscle injury and repair.

James G. Tidball (2005)

Modified muscle use or injury can produce a stereotypic inflammatory response in which neutrophils rapidly invade, followed by macrophages. This inflammatory response coincides with muscle repair, regeneration, and growth, which involve activation and proliferation of satellite cells, followed by their terminal differentiation. Recent investigations have begun to explore the relationship between inflammatory cell functions and skeletal muscle injury and repair by using genetically modified animal models, antibody depletions of specific inflammatory cell populations, or expression profiling of inflamed muscle after injury. These studies have contributed to a complex picture in which inflammatory cells promote both injury and repair, through the combined actions of free radicals, growth factors, and chemokines. In this review, recent discoveries concerning the interactions between skeletal muscle and inflammatory cells are presented. New findings clearly show a role for neutrophils in promoting muscle damage soon after muscle injury or modified use. No direct evidence is yet available to show that neutrophils play a beneficial role in muscle repair or regeneration. Macrophages have also been shown capable of promoting muscle damage in vivo and in vitro through the release of free radicals, although other findings indicate that they may also play a role in muscle repair and regeneration through growth factors and cytokine-mediated signaling. However, this role for macrophages in muscle regeneration is still not definitive; other cells present in muscle can also produce the potentially regenerative factors, and it remains to be proven whether macrophage-derived factors are essential for muscle repair or regeneration in vivo. New evidence also shows that muscle cells can release positive and negative regulators of inflammatory cell invasion, and thereby play an active role in modulating the inflammatory process. In particular, muscle-derived nitric oxide can inhibit inflammatory cell invasion of healthy muscle and protect muscle from lysis by inflammatory cells in vivo and in vitro. On the other hand, muscle-derived cytokines can signal for inflammatory cell invasion, at least in vitro. The immediate challenge for advancing our current understanding of the relationships between muscle and inflammatory cells during muscle injury and repair is to place what has been learned in vitro into the complex and dynamic in vivo environment.

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Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering.

Jessica Williams, Adebisi Adewunmi, Rachel Schek … (2005)

Polycaprolactone (PCL) is a bioresorbable polymer with potential applications for bone and cartilage repair. In this work, porous PCL scaffolds were computationally designed and then fabricated via selective laser sintering (SLS), a rapid prototyping technique. The microstructure and mechanical properties of the fabricated scaffolds were assessed and compared to the designed porous architectures and computationally predicted properties. Scaffolds were then seeded with bone morphogenetic protein-7 (BMP-7) transduced fibroblasts and implanted subcutaneously to evaluate biological properties and to demonstrate tissue in-growth. The work done illustrates the ability to design and fabricate PCL scaffolds with porous architecture that have sufficient mechanical properties for bone tissue engineering applications using SLS. Compressive modulus and yield strength values ranged from 52 to 67 MPa and 2.0 to 3.2 Mpa, respectively, lying within the lower range of properties reported for human trabecular bone. Finite element analysis (FEA) results showed that mechanical properties of scaffold designs and of fabricated scaffolds can be computationally predicted. Histological evaluation and micro-computed tomography (microCT) analysis of implanted scaffolds showed that bone can be generated in vivo. Finally, to demonstrate the clinical application of this technology, we designed and fabricated a prototype mandibular condyle scaffold based on an actual pig condyle. The integration of scaffold computational design and free-form fabrication techniques presented here could prove highly useful for the construction of scaffolds that have anatomy specific exterior architecture derived from patient CT or MRI data and an interior porous architecture derived from computational design optimization.

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Author and article information

Journal

Journal ID (nlm-ta): Materials (Basel)

Journal ID (iso-abbrev): Materials (Basel)

Journal ID (publisher-id): materials

Title: Materials

Publisher: MDPI

ISSN (Electronic): 1996-1944

Publication date (Electronic): 29 May 2020

Publication date Collection: June 2020

Volume: 13

Issue: 11

Electronic Location Identifier: 2483

Affiliations

[1 ]Fondazione Istituto di Ricerca Pediatrica Città della Speranza, 35127 Padova, Italy; edoardo.maghin@ 123456phd.unipd.it (E.M.); eugenia.carraro@ 123456studenti.unipd.it (E.C.); mattiagiagante@ 123456gmail.com (M.G.); piero.pavan@ 123456unipd.it (P.P.)

[2 ]Department of Industrial Engineering, University of Padova, 35131 Padova, Italy

[3 ]Department of Women and Children Health, University of Padova, 35128 Padova, Italy

[4 ]Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy

Author notes

[* ]Correspondence: d.boso@ 123456irpcds.org (D.B.); m.piccoli@ 123456irpcds.org (M.P.)

Author information

Daniele Boso https://orcid.org/0000-0001-9919-1764

Martina Piccoli https://orcid.org/0000-0001-6211-0051

Article

Publisher ID: materials-13-02483

DOI: 10.3390/ma13112483

PMC ID: 7321144

PubMed ID: 32486040

SO-VID: 7d5285da-ca35-49e8-82ae-a2cb5d999be3

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Extracellular Matrix-Derived Hydrogels as Biomaterial for Different Skeletal Muscle Tissue Replacements

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Abstract

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Most cited references 99

Skeletal muscle: a brief review of structure and function.

Inflammatory processes in muscle injury and repair.

Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering.

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