Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.9
5.1
Journals
Cells
Special Issues
Tissue Engineered Models of Musculoskeletal Regeneration and Pathologies
share announcement

Tissue Engineered Models of Musculoskeletal Regeneration and Pathologies

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Tissues and Organs".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 17051

Special Issue Editors

Prof. Dr. Boris Michael Holzapfel

E-Mail Website
Guest Editor
Department of Orthopaedics and Traumatology, Musculoskeletal University Center Munich (MUM), University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany
Interests: hip & knee arthroplasty; musculoskeletal oncology; tissue engineering & regenerative medicine
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Susanne Mayer

E-Mail Website
Guest Editor
Department of Orthopaedics and Traumatology, Musculoskeletal UniversityCenter Munich (MUM), University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany
Interests: tissue engineering; bone; chondrocytes; osteoclastogenesis

Special Issue Information

Dear Colleagues,

The recent literature indicates that successful translational musculoskeletal research relies on appropriate models, both in vitro and in vivo, to develop new diagnostic tools or cutting-edge therapeutic strategies.

Within this context, we need to critically assess the value of traditionally used model systems. Our lack of effectiveness is particularly evident in traditional drug development and testing. It has been demonstrated that the majority of novel drug candidates tested in clinical trials are ineffective, even though they have previously undergone successful preclinical testing—and for those few candidates that have been proven to be clinically effective, it usually takes years and millions of dollars to get them through regulatory approval.

From a translational medicine perspective, we have to increase the efficacy of our model systems in order to close the translation gap that musculoskeletal medicine suffers from. The concept of tissue engineering and regenerative medicine (TE&RM) offers the unique opportunity to move a step forward from simple tissue culture models to smart three-dimensional in vitro systems that incorporate not only healthy or diseased cells of interest but also their complex cellular and extracellular natural microenvironments. These modular systems are scalable and they can be customized in a plethora of different ways in order to serve the purpose of personalized musculoskeletal medicine. Moreover, the establishment of genetically altered immunocompromised murine hosts have made it possible to incorporate humanized complex multicellular and polyhierarchical tissue engineered organ systems to study human musculoskeletal diseases and regeneration under in vivo conditions.

Recognizing that a model cannot be perfect, the incorporation of TE&RM principles is still a first and small step towards the establishment of humanized model systems that we can use to predict outcomes in musculoskeletal medicine. With the present Special Issue, we want to give you an overview of those new tissue engineered platforms that are potentially able to revolutionize the way we model human musculoskeletal disease and regeneration.  

Prof. Dr. Boris Michael Holzapfel
Prof. Dr. Susanne Mayer
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. Cells is an international peer-reviewed open access semimonthly 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

  • tissue engineering
  • musculoskeletal
  • disease
  • regeneration
  • microenvironment
  • cells
  • extracellular matrix

Published Papers (6 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

23 pages, 24440 KiB  
Article
Zinc-Doped Bioactive Glass/Polycaprolactone Hybrid Scaffolds Manufactured by Direct and Indirect 3D Printing Methods for Bone Regeneration
by Nafise Elahpour, Isabella Niesner, Cédric Bossard, Nora Abdellaoui, Valérie Montouillout, Franck Fayon, Christine Taviot-Guého, Tina Frankenbach, Alexander Crispin, Pardis Khosravani, Boris Michael Holzapfel, Edouard Jallot, Susanne Mayer-Wagner and Jonathan Lao
Cells 2023, 12(13), 1759; https://doi.org/10.3390/cells12131759 - 30 Jun 2023
Cited by 1 | Viewed by 1867
Abstract
A novel organic–inorganic hybrid, based on SiO2-CaO-ZnO bioactive glass (BG) and polycaprolactone (PCL), associating the highly bioactive and versatile bioactive glass with clinically established PCL was examined. The BG–PCL hybrid is obtained by acid-catalyzed silica sol–gel process inside PCL solution either [...] Read more.
A novel organic–inorganic hybrid, based on SiO2-CaO-ZnO bioactive glass (BG) and polycaprolactone (PCL), associating the highly bioactive and versatile bioactive glass with clinically established PCL was examined. The BG–PCL hybrid is obtained by acid-catalyzed silica sol–gel process inside PCL solution either by direct or indirect printing. Apatite-formation tests in simulated body fluid (SBF) confirm the ion release along with the hybrid’s bone-like apatite forming. Kinetics differ significantly between directly and indirectly printed scaffolds, the former requiring longer periods to degrade, while the latter demonstrates faster calcium phosphate (CaP) formation. Remarkably, Zn diffusion and accumulation are observed at the surface within the newly formed active CaP layer. Zn release is found to be dependent on printing method and immersion medium. Investigation of BG at the atomic scale reveals the ambivalent role of Zn, capable of acting both as a network modifier and as a network former linking the BG silicate network. In addition, hMSCs viability assay proves no cytotoxicity of the Zn hybrid. LIVE/DEAD staining demonstrated excellent cell viability and proliferation for over seven weeks. Overall, this hybrid material either non-doped or doped with a metal trace element is a promising candidate to be translated to clinical applications for bone regeneration. Full article
(This article belongs to the Special Issue Tissue Engineered Models of Musculoskeletal Regeneration and Pathologies)
►▼ Show Figures

Graphical abstract

27 pages, 8226 KiB  
Article
Triphasic 3D In Vitro Model of Bone-Tendon-Muscle Interfaces to Study Their Regeneration
by Wendy Balestri, Graham J. Hickman, Robert H. Morris, John A. Hunt and Yvonne Reinwald
Cells 2023, 12(2), 313; https://doi.org/10.3390/cells12020313 - 13 Jan 2023
Cited by 5 | Viewed by 2621
Abstract
The transition areas between different tissues, known as tissue interfaces, have limited ability to regenerate after damage, which can lead to incomplete healing. Previous studies focussed on single interfaces, most commonly bone-tendon and bone-cartilage interfaces. Herein, we develop a 3D in vitro model [...] Read more.
The transition areas between different tissues, known as tissue interfaces, have limited ability to regenerate after damage, which can lead to incomplete healing. Previous studies focussed on single interfaces, most commonly bone-tendon and bone-cartilage interfaces. Herein, we develop a 3D in vitro model to study the regeneration of the bone-tendon-muscle interface. The 3D model was prepared from collagen and agarose, with different concentrations of hydroxyapatite to graduate the tissues from bones to muscles, resulting in a stiffness gradient. This graduated structure was fabricated using indirect 3D printing to provide biologically relevant surface topographies. MG-63, human dermal fibroblasts, and Sket.4U cells were found suitable cell models for bones, tendons, and muscles, respectively. The biphasic and triphasic hydrogels composing the 3D model were shown to be suitable for cell growth. Cells were co-cultured on the 3D model for over 21 days before assessing cell proliferation, metabolic activity, viability, cytotoxicity, tissue-specific markers, and matrix deposition to determine interface formations. The studies were conducted in a newly developed growth chamber that allowed cell communication while the cell culture media was compartmentalised. The 3D model promoted cell viability, tissue-specific marker expression, and new matrix deposition over 21 days, thereby showing promise for the development of new interfaces. Full article
(This article belongs to the Special Issue Tissue Engineered Models of Musculoskeletal Regeneration and Pathologies)
►▼ Show Figures

Figure 1

18 pages, 16942 KiB  
Article
Effects of Endochondral and Intramembranous Ossification Pathways on Bone Tissue Formation and Vascularization in Human Tissue-Engineered Grafts
by Jonathan C. Bernhard, Darja Marolt Presen, Ming Li, Xavier Monforte, James Ferguson, Gabriele Leinfellner, Patrick Heimel, Susanna L. Betti, Sharon Shu, Andreas H. Teuschl-Woller, Stefan Tangl, Heinz Redl and Gordana Vunjak-Novakovic
Cells 2022, 11(19), 3070; https://doi.org/10.3390/cells11193070 - 29 Sep 2022
Cited by 10 | Viewed by 3082
Abstract
Bone grafts can be engineered by differentiating human mesenchymal stromal cells (MSCs) via the endochondral and intramembranous ossification pathways. We evaluated the effects of each pathway on the properties of engineered bone grafts and their capacity to drive bone regeneration. Bone-marrow-derived MSCs were [...] Read more.
Bone grafts can be engineered by differentiating human mesenchymal stromal cells (MSCs) via the endochondral and intramembranous ossification pathways. We evaluated the effects of each pathway on the properties of engineered bone grafts and their capacity to drive bone regeneration. Bone-marrow-derived MSCs were differentiated on silk scaffolds into either hypertrophic chondrocytes (hyper) or osteoblasts (osteo) over 5 weeks of in vitro cultivation, and were implanted subcutaneously for 12 weeks. The pathways’ constructs were evaluated over time with respect to gene expression, composition, histomorphology, microstructure, vascularization and biomechanics. Hypertrophic chondrocytes expressed higher levels of osteogenic genes and deposited significantly more bone mineral and proteins than the osteoblasts. Before implantation, the mineral in the hyper group was less mature than that in the osteo group. Following 12 weeks of implantation, the hyper group had increased mineral density but a similar overall mineral composition compared with the osteo group. The hyper group also displayed significantly more blood vessel infiltration than the osteo group. Both groups contained M2 macrophages, indicating bone regeneration. These data suggest that, similar to the body’s repair processes, endochondral pathway might be more advantageous when regenerating large defects, whereas intramembranous ossification could be utilized to guide the tissue formation pattern with a scaffold architecture. Full article
(This article belongs to the Special Issue Tissue Engineered Models of Musculoskeletal Regeneration and Pathologies)
►▼ Show Figures

Graphical abstract

14 pages, 981 KiB  
Article
Inhibition of TNF-α Restores Muscle Force, Inhibits Inflammation, and Reduces Apoptosis of Traumatized Skeletal Muscles
by Ioannis Stratos, Ann-Kathrin Behrendt, Christian Anselm, Aldebarani Gonzalez, Thomas Mittlmeier and Brigitte Vollmar
Cells 2022, 11(15), 2397; https://doi.org/10.3390/cells11152397 - 3 Aug 2022
Cited by 12 | Viewed by 2551
Abstract
Background: Muscle injuries are common in humans and are often associated with irrecoverable damage and disability. Upon muscle injury, TNF-α signaling pathways modulate the healing process and are predominantly associated with tissue degradation. In this study we assumed that TNF-α inhibition could reduce [...] Read more.
Background: Muscle injuries are common in humans and are often associated with irrecoverable damage and disability. Upon muscle injury, TNF-α signaling pathways modulate the healing process and are predominantly associated with tissue degradation. In this study we assumed that TNF-α inhibition could reduce the TNF-α-associated tissue degradation after muscle injury. Materials and methods: Therefore, the left soleus muscle of 42 male Wistar rats was injured using a standardized open muscle injury model. All rats were treated immediately after injury either with infliximab (single i.p. injection; 10 mg/kg b.w.) or saline solution i.p. Final measurements were conducted at day one, four, and 14 post injury. The muscle force, the muscle cell proliferation, the muscle cell coverage as well as the myofiber diameter served as read out parameters of our experiment. Results: Systemic application of infliximab could significantly reduce the TNF-α levels in the injured muscle at day four upon trauma compared to saline treated animals. The ratio of muscle weight to body weight was increased and the twitch muscle force showed a significant rise 14 days after trauma and TNF-α inhibition. Quantification of myofiber diameter in the penumbra zone showed a significant difference between both groups at day one and four after injury, indicated by muscle hypertrophy in the infliximab group. Planimetric analysis of the injured muscle at day 14 revealed increased muscle tissue fraction in the infliximab group compared to the control animals. Muscle cell proliferation did not differ between both groups. Conclusions: These data provide evidence that the TNF-α blockade positively regulates the restauration of skeletal muscles upon injury. Full article
(This article belongs to the Special Issue Tissue Engineered Models of Musculoskeletal Regeneration and Pathologies)
►▼ Show Figures

Graphical abstract

22 pages, 5789 KiB  
Article
Enthesis Healing Is Dependent on Scaffold Interphase Morphology—Results from a Rodent Patellar Model
by Carlos J. Peniche Silva, Sebastian A. Müller, Nicholas Quirk, Patrina S. P. Poh, Carla Mayer, Antonella Motta, Claudio Migliaresi, Michael J. Coenen, Christopher H. Evans, Elizabeth R. Balmayor and Martijn van Griensven
Cells 2022, 11(11), 1752; https://doi.org/10.3390/cells11111752 - 26 May 2022
Cited by 6 | Viewed by 2957
Abstract
The use of multiphasic scaffolds to treat injured tendon-to-bone entheses has shown promising results in vitro. Here, we used two versions of a biphasic silk fibroin scaffold to treat an enthesis defect created in a rat patellar model in vivo. One version presented [...] Read more.
The use of multiphasic scaffolds to treat injured tendon-to-bone entheses has shown promising results in vitro. Here, we used two versions of a biphasic silk fibroin scaffold to treat an enthesis defect created in a rat patellar model in vivo. One version presented a mixed transition between the bony and the tendon end of the construct (S-MT) while this transition was abrupt in the second version (S-AT). At 12 weeks after surgery, the S-MT scaffold promoted better healing of the injured enthesis, with minimal undesired ossification of the insertion area. The expression of tenogenic and chondrogenic markers was sustained for longer in the S-MT-treated group and the tangent modulus of the S-MT-treated samples was similar to the native tissue at 12 weeks while that of the S-AT-treated enthesis was lower. Our study highlights the important role of the transition zone of multiphasic scaffolds in the treatment of complex interphase tissues such as the tendon-to-bone enthesis. Full article
(This article belongs to the Special Issue Tissue Engineered Models of Musculoskeletal Regeneration and Pathologies)
►▼ Show Figures

Graphical abstract

Review

Jump to: Research

20 pages, 2991 KiB  
Review
Articular Cartilage Regeneration through Bioassembling Spherical Micro-Cartilage Building Blocks
by Brian E. Grottkau, Zhixin Hui and Yonggang Pang
Cells 2022, 11(20), 3244; https://doi.org/10.3390/cells11203244 - 16 Oct 2022
Cited by 2 | Viewed by 2927
Abstract
Articular cartilage lesions are prevalent and affect one out of seven American adults and many young patients. Cartilage is not capable of regeneration on its own. Existing therapeutic approaches for articular cartilage lesions have limitations. Cartilage tissue engineering is a promising approach for [...] Read more.
Articular cartilage lesions are prevalent and affect one out of seven American adults and many young patients. Cartilage is not capable of regeneration on its own. Existing therapeutic approaches for articular cartilage lesions have limitations. Cartilage tissue engineering is a promising approach for regenerating articular neocartilage. Bioassembly is an emerging technology that uses microtissues or micro-precursor tissues as building blocks to construct a macro-tissue. We summarize and highlight the application of bioassembly technology in regenerating articular cartilage. We discuss the advantages of bioassembly and present two types of building blocks: multiple cellular scaffold-free spheroids and cell-laden polymer or hydrogel microspheres. We present techniques for generating building blocks and bioassembly methods, including bioprinting and non-bioprinting techniques. Using a data set of 5069 articles from the last 28 years of literature, we analyzed seven categories of related research, and the year trends are presented. The limitations and future directions of this technology are also discussed. Full article
(This article belongs to the Special Issue Tissue Engineered Models of Musculoskeletal Regeneration and Pathologies)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-6
Back to TopTop