Electrospinning and Additive Manufacturing: Biofabrication Strategies to Guide Cells in Musculoskeletal Tissue Regeneration

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Methods".

Deadline for manuscript submissions: closed (20 March 2023) | Viewed by 15317

Special Issue Editors


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Guest Editor
Interdepartmental Centre for Industrial Research in Advanced Mechanical Engineering Applications and Materials Technology, Alma Mater Studiorum – Università di Bologna, Bologna, Italy
Interests: electrospinning; hierarchical electrospun scaffolds; musculoskeletal tissue regeneration; biofabrication; biomechanical characterization of scaffolds

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Guest Editor
School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK
Interests: musculoskeletal tissue regeneration; orthopaedic implants; stem cells

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Guest Editor
Department Cell Biology-Inspired Tissue Engineering (cBITE), MERLN Institute for Technology-Inspired Tissue Regeneration, Maastricht University, the Netherlands
Interests: co-morbidities; interface regeneration; molecular regeneration; translational regenerative medicine

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Guest Editor
Department Complex Tissue Regeneration (CTR), MERLN Institute for Technology-Inspired Tissue Regeneration, Maastricht University, Maastricht, The Netherlands
Interests: biofabrication; stem cells; regenerative medicine; tissue engineering
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Special Issue Information

Dear Colleagues,

Inspired by nature, researchers have developed several strategies to produce scaffolds mimicking the structure and properties of biological tissues based on a multiscale philosophy. This complex morphomechanical approach is fundamental for guiding cellular proliferation, growth, differentiation, and, ultimately, in regenerating the target musculoskeletal tissues. Among the various technologies being explored, electrospinning and additive manufacturing (i.e., 3D printing, bioprinting, etc.) are some of the most promising, allowing reproduction of the hierarchical structure and biomechanical properties of a wide panel of tissues such as tendons, ligaments, muscles, cartilage, bone, and their interfaces. Moreover, the functionalization and mechanical stimulation of these complex scaffolds have been shown to enhance cell proliferation and determine stem cell fate.

In this Special Issue, we would like to present a collection of papers and reviews showing how innovative electrospun and additive manufacturing scaffolds can enhance cellular proliferation and guide stem cell differentiation and musculoskeletal tissue regeneration.

Dr. Alberto Sensini
Prof. Dr. Gordon Blunn
Prof. Dr. Martijn van Griensven
Prof. Dr. Lorenzo Moroni
Guest Editors

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Keywords

  • electrospinning
  • additive manufacturing
  • scaffold architecture/structure
  • 3D printing/bioprinting
  • static/dynamic cell cultures
  • musculoskeletal tissue regeneration
  • stem cell differentiation

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Published Papers (4 papers)

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Research

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16 pages, 5327 KiB  
Article
Mechanical and Biological Evaluation of Melt-Electrowritten Polycaprolactone Scaffolds for Acetabular Labrum Restoration
by Matthias X. T. Santschi, Stephanie Huber, Jan Bujalka, Nouara Imhof, Michael Leunig and Stephen J. Ferguson
Cells 2022, 11(21), 3450; https://doi.org/10.3390/cells11213450 - 31 Oct 2022
Cited by 5 | Viewed by 2126
Abstract
Repair or reconstruction of a degenerated or injured acetabular labrum is essential to the stability and health of the hip joint. Current methods for restoration fail to reproduce the structure and mechanical properties of the labrum. In this study, we characterized the structure [...] Read more.
Repair or reconstruction of a degenerated or injured acetabular labrum is essential to the stability and health of the hip joint. Current methods for restoration fail to reproduce the structure and mechanical properties of the labrum. In this study, we characterized the structure and tensile mechanical properties of melt-electrowritten polycaprolactone scaffolds of varying architectures and assessed the labrum cell compatibility of selected graft candidates. Cell compatibility was assessed using immunofluorescence of the actin skeleton. First, labrum explants were co-cultured with scaffold specimen to investigate the scaffold compatibility with primary cells. Second, effects of pore size on pre-cultured seeded labrum cells were studied. Third, cell compatibility under dynamic stretching was examined. Grid-like structures showed favorable tensile properties with decreasing fibre spacing. Young’s moduli ranging from 2.33 ± 0.34 to 13.36 ± 2.59 MPa were measured across all structures. Primary labrum cells were able to migrate from co-cultured labrum tissue specimens into the scaffold and grow in vitro. Incorporation of small-diameter-fibre and interfibre spacing improved cell distribution and cell spreading, whereas mechanical properties were only marginally affected. Wave-patterned constructs reproduced the non-linear elastic behaviour of native labrum tissue and, therefore, allowed for physiological cyclic tensile strain but showed decreased cell compatibility under dynamic loading. In conclusion, melt-electrowritten polycaprolactone scaffolds are promising candidates for labral grafts; however, further development is required to improve both the mechanical and biological compatibility. Full article
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16 pages, 4271 KiB  
Article
Combined Effects of Polydopamine-Assisted Copper Immobilization on 3D-Printed Porous Ti6Al4V Scaffold for Angiogenic and Osteogenic Bone Regeneration
by Hsi-Yao Wu, Yen-Hong Lin, Alvin Kai-Xing Lee, Ting-You Kuo, Chun-Hao Tsai and Ming-You Shie
Cells 2022, 11(18), 2824; https://doi.org/10.3390/cells11182824 - 9 Sep 2022
Cited by 18 | Viewed by 2614
Abstract
Numerous studies have demonstrated that biological compounds and trace elements such as dopamine (DA) and copper ions (Cu) could be modified onto the surfaces of scaffolds using a one-step immersion process which is simple, inexpensive and, most importantly, non-cytotoxic. The development and emergence [...] Read more.
Numerous studies have demonstrated that biological compounds and trace elements such as dopamine (DA) and copper ions (Cu) could be modified onto the surfaces of scaffolds using a one-step immersion process which is simple, inexpensive and, most importantly, non-cytotoxic. The development and emergence of 3D printing technologies such as selective laser melting (SLM) have also made it possible for us to fabricate bone scaffolds with precise structural designs using metallic compounds. In this study, we fabricated porous titanium scaffolds (Ti) using SLM and modified the surface of Ti with polydopamine (PDA) and Cu. There are currently no other reported studies with such a combination for osteogenic and angiogenic-related applications. Results showed that such modifications did not affect general appearances and microstructural characteristics of the porous Ti scaffolds. This one-step immersion modification allowed us to modify the surfaces of Ti with different concentrations of Cu ions, thus allowing us to fabricate individualized scaffolds for different clinical scenarios. The modification improved the hydrophilicity and surface roughness of the scaffolds, which in turn led to promote cell behaviors of Wharton’s jelly mesenchymal stem cells. Ti itself has high mechanical strength, therefore making it suitable for surgical handling and clinical applications. Furthermore, the scaffolds were able to release ions in a sustained manner which led to an upregulation of osteogenic-related proteins (bone alkaline phosphatase, bone sialoprotein and osteocalcin) and angiogenic-related proteins (vascular endothelial growth factor and angiopoietin-1). By combining additive manufacturing, Ti6Al4V scaffolds, surface modification and Cu ions, the novel hybrid 3D-printed porous scaffold could be fabricated with ease and specifically benefited future bone regeneration in the clinic. Full article
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17 pages, 32305 KiB  
Article
Influence of ROCK Pathway Manipulation on the Actin Cytoskeleton Height
by Carolin Grandy, Fabian Port, Jonas Pfeil and Kay-Eberhard Gottschalk
Cells 2022, 11(3), 430; https://doi.org/10.3390/cells11030430 - 26 Jan 2022
Cited by 10 | Viewed by 4196
Abstract
The actin cytoskeleton with its dynamic properties serves as the driving force for the movement and division of cells and gives the cell shape and structure. Disorders in the actin cytoskeleton occur in many diseases. Deeper understanding of its regulation is essential in [...] Read more.
The actin cytoskeleton with its dynamic properties serves as the driving force for the movement and division of cells and gives the cell shape and structure. Disorders in the actin cytoskeleton occur in many diseases. Deeper understanding of its regulation is essential in order to better understand these biochemical processes. In our study, we use metal-induced energy transfer (MIET) as a tool to quantitatively examine the rarely considered third dimension of the actin cytoskeleton with nanometer accuracy. In particular, we investigate the influence of different drugs acting on the ROCK pathway on the three-dimensional actin organization. We find that cells treated with inhibitors have a lower actin height to the substrate while treatment with a stimulator for the ROCK pathway increases the actin height to the substrate, while the height of the membrane remains unchanged. This reveals the precise tuning of adhesion and cytoskeleton tension, which leads to a rich three-dimensional structural behaviour of the actin cytoskeleton. This finetuning is differentially affected by either inhibition or stimulation. The high axial resolution shows the importance of the precise finetuning of the actin cytoskeleton and the disturbed regulation of the ROCK pathway has a significant impact on the actin behavior in the z dimension. Full article
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Review

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40 pages, 2812 KiB  
Review
Scaffold-Mediated Immunoengineering as Innovative Strategy for Tendon Regeneration
by Valentina Russo, Mohammad El Khatib, Giuseppe Prencipe, Adrián Cerveró-Varona, Maria Rita Citeroni, Annunziata Mauro, Paolo Berardinelli, Melisa Faydaver, Arlette A. Haidar-Montes, Maura Turriani, Oriana Di Giacinto, Marcello Raspa, Ferdinando Scavizzi, Fabrizio Bonaventura, Liliana Liverani, Aldo R. Boccaccini and Barbara Barboni
Cells 2022, 11(2), 266; https://doi.org/10.3390/cells11020266 - 13 Jan 2022
Cited by 22 | Viewed by 4800
Abstract
Tendon injuries are at the frontier of innovative approaches to public health concerns and sectoral policy objectives. Indeed, these injuries remain difficult to manage due to tendon’s poor healing ability ascribable to a hypo-cellularity and low vascularity, leading to the formation of a [...] Read more.
Tendon injuries are at the frontier of innovative approaches to public health concerns and sectoral policy objectives. Indeed, these injuries remain difficult to manage due to tendon’s poor healing ability ascribable to a hypo-cellularity and low vascularity, leading to the formation of a fibrotic tissue affecting its functionality. Tissue engineering represents a promising solution for the regeneration of damaged tendons with the aim to stimulate tissue regeneration or to produce functional implantable biomaterials. However, any technological advancement must take into consideration the role of the immune system in tissue regeneration and the potential of biomaterial scaffolds to control the immune signaling, creating a pro-regenerative environment. In this context, immunoengineering has emerged as a new discipline, developing innovative strategies for tendon injuries. It aims at designing scaffolds, in combination with engineered bioactive molecules and/or stem cells, able to modulate the interaction between the transplanted biomaterial-scaffold and the host tissue allowing a pro-regenerative immune response, therefore hindering fibrosis occurrence at the injury site and guiding tendon regeneration. Thus, this review is aimed at giving an overview on the role exerted from different tissue engineering actors in leading immunoregeneration by crosstalking with stem and immune cells to generate new paradigms in designing regenerative medicine approaches for tendon injuries. Full article
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