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Ligament/Tendon and Cartilage Tissue Engineering and Reconstruction
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Ligament/Tendon and Cartilage Tissue Engineering and Reconstruction

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 20 August 2025 | Viewed by 4205

Special Issue Editor

Prof. Dr. Gundula Schulze-Tanzil

E-Mail Website
Guest Editor
Institute of Anatomy and Cell Biology, Paracelsus Medical University, Nuremberg and Salzburg, 90419 Nuremberg, Germany
Interests: ligament/tendon; cartilage; tissue engineering and reconstruction
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Ligaments, tendons and cartilage share many tissue characteristics, such as the following: a poor or absent blood supply, a low cell content, and an abundant collagenous extracellular matrix. Some of these properties may explain their limited self-healing capacity during tissue injury.

Hence, tissue engineering (TE) represents a promising strategy for tissue reconstruction. Using novel biomimetic biomaterials as chondro-/tenogenic cell carriers represents an innovative culturing approach; e.g., using smart bioreactors and versatile bioprinting strategies could support the regeneration of these tissues with tissue engineered implants. Cells recruited for TE, the tailored release of bioactive factors, and targeted cell lineage differentiation are also of interest. Novel data describing in vivo TE results gained using animal models are also welcome.

Lead by Prof. Dr. Gundula Schulze-Tanzil and assisted by our Topical Advisory Panel Member, Dr. Clemens Gögele (Paracelsus Medical University), this Special Issue will focus on the most recent developments in tendon/ligament and cartilage tissue engineering, comprising in vitro and in vivo studies.

Prof. Dr. Gundula Schulze-Tanzil
Guest Editor

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • cartilage
  • tendon
  • ligament
  • anterior cruciate ligament
  • bioprinting
  • scaffold
  • bioreactor
  • tissue engineering

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Published Papers (4 papers)

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Research

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24 pages, 3587 KiB  
Article
Neural Markers Predict Tendon Healing Outcomes in an Ovine Achilles Tendon Injury Model: Spontaneous Repair Versus Amniotic Epithelial Cell-Induced Regeneration
by Valeria Giovanna Festinese, Melisa Faydaver, Delia Nardinocchi, Oriana Di Giacinto, Mohammad El Khatib, Annunziata Mauro, Maura Turriani, Angelo Canciello, Paolo Berardinelli, Valentina Russo and Barbara Barboni
Int. J. Mol. Sci. 2025, 26(6), 2445; https://doi.org/10.3390/ijms26062445 - 9 Mar 2025
Viewed by 577
Abstract
Tendon injuries pose a clinical challenge due to tendons’ limited recovery. Emerging evidence points to the nervous system’s critical role in tendon healing, with neural markers NGF, NF-200, NPY, CGRP, and GAL modulating inflammation, cell proliferation, and extracellular matrix (ECM) remodeling. This study [...] Read more.
Tendon injuries pose a clinical challenge due to tendons’ limited recovery. Emerging evidence points to the nervous system’s critical role in tendon healing, with neural markers NGF, NF-200, NPY, CGRP, and GAL modulating inflammation, cell proliferation, and extracellular matrix (ECM) remodeling. This study investigates the predictive role of selected neural markers in a validated ovine Achilles tendon injury model, comparing spatio-temporal expression patterns in regenerating tendons transplanted with amniotic epithelial stem cells (AECs) versus spontaneous healing (CTR) 14 and 28 days post-injury (p.i.). AEC-treated tissues showed a spatio-temporal modulation of NF-200, NGF, NPY, CGRP, GAL, and enhanced ECM remodeling, with greater cell alignment, lower angle deviation, and accelerated collagen maturation, with a favorable Collagen type 1 (COL1) to Collagen type 3 (COL3) ratio. Pearson’s matrix analysis revealed significant positive correlations between NGF, CGRP, and GAL expression, along a positive correlation between the three neural markers and cell alignment and angle deviation. As opposed to CTR, in AEC-treated tendons, lower levels of NGF, CGRP, and GAL correlated positively with improved tissue organization, suggesting these markers may predict successful tendon regeneration. The findings highlight the neuro-mediated activity of AECs in tendon regeneration, with NGF, CGRP, and GAL emerging as key predictive biomarkers for tendon healing. Full article
(This article belongs to the Special Issue Ligament/Tendon and Cartilage Tissue Engineering and Reconstruction)
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13 pages, 2804 KiB  
Article
Efficacy of Light-Emitting Diode-Mediated Photobiomodulation in Tendon Healing in a Murine Model
by Jae Kyung Lim, Jae Ho Kim, Gyu Tae Park, Seung Hun Woo, Minkyoung Cho and Suk Woong Kang
Int. J. Mol. Sci. 2025, 26(5), 2286; https://doi.org/10.3390/ijms26052286 - 4 Mar 2025
Viewed by 812
Abstract
The application of light-emitting diode (LED)-dependent photobiomodulation (PBM) in promoting post-tendon injury healing has been recently reported. Despite establishing a theoretical basis for ligament restoration through PBM, identifying effective LED wavelength combinations and ensuring safety in animal models remain unresolved challenges. In our [...] Read more.
The application of light-emitting diode (LED)-dependent photobiomodulation (PBM) in promoting post-tendon injury healing has been recently reported. Despite establishing a theoretical basis for ligament restoration through PBM, identifying effective LED wavelength combinations and ensuring safety in animal models remain unresolved challenges. In our previous study, we demonstrated that combined irradiation at 630 nm and 880 nm promotes cell proliferation and migration, which are critical processes during the early stage of tendon healing in human-derived tendon fibroblasts. Based on this, we hypothesized that 630/880 nm LED-based PBM might promote rapid healing during the initial phase of tendon healing, and we aimed to analyze the results after PBM treatment in a murine model. Migration kinetics were analyzed at two specific wavelengths: 630 and 880 nm. The Achilles tendon in the hind limbs of Balb/c mice was severed by Achilles tendon transection. Subsequently, the mice were randomized into LED non-irradiation and LED irradiation groups. Mice with intact tendons were employed as healthy controls. The total number of mice was 13 for the healthy and injured groups and 14 for the LED-irradiated injured group, and the data presented in this manuscript were obtained from one representative experiment (n = 4–5 per group). The wounds were LED-irradiated for 20 min daily for two days. Histological properties, tendon healing mediators, and inflammatory mediators were screened on day 14. The roundness of the nuclei and fiber structure, indicating the degree of infiltrated inflammatory cells and severity of fiber fragmentation, respectively, were lower in the LED irradiation group than in the LED non-irradiation group. Immunohistochemical analysis depicted an increase in tenocytes (SCX+ cells) and recovery of wounds with reduced fibrosis (lower collagen 3 and TGF-β1) in the LED irradiation group during healing; conversely, the LED non-irradiation group exhibited tissue fibrosis. Overall, the ratio of M2 macrophages to total macrophages in the LED irradiation group was higher than that in the injured group. LED-based PBM in the Achilles tendon rupture murine model facilitated a rapid restoration of histological and immunochemical outcomes. These findings suggest that LED-based PBM presents remarkable potential as an adjunct therapeutic approach for tendon healing and warrants further research to standardize various parameters to advance and establish it as a reliable treatment regimen. Full article
(This article belongs to the Special Issue Ligament/Tendon and Cartilage Tissue Engineering and Reconstruction)
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18 pages, 10234 KiB  
Article
Effect of Collagen Coating and Fiber Profile on Tenocyte Growth on Braided Poly-ε-Caprolactone Scaffolds for Tendon and Ligament Regeneration
by Caroline Emonts, Benedict Bauer, Charlotte Büchter, Thomas Pufe, Thomas Gries and Mersedeh Tohidnezhad
Int. J. Mol. Sci. 2025, 26(4), 1735; https://doi.org/10.3390/ijms26041735 - 18 Feb 2025
Viewed by 531
Abstract
Using scaffolds is a promising alternative to current methods of treatment for ruptures of tendons and ligaments. However, scaffolds are subject to a wide range of challenges, including mechanical, degradation, process-related and biological requirements. Poly-ε-caprolactone (PCL) fibers have already shown potential for tendon [...] Read more.
Using scaffolds is a promising alternative to current methods of treatment for ruptures of tendons and ligaments. However, scaffolds are subject to a wide range of challenges, including mechanical, degradation, process-related and biological requirements. Poly-ε-caprolactone (PCL) fibers have already shown potential for tendon tissue engineering (TTE) because of their degradation kinetics and excellent mechanical properties. The objective of this study was to enhance the PCL scaffold for TTE, specifically in regard to the filament morphology and collagen coating. PCL fibers were melt-spun as monofilaments with circular and snowflake-shaped cross-sections. Different scaffold densities were achieved by applying three different braiding angles in the braiding process. Morphological characterization was conducted including porosity and pore size distribution using µ-CT. The scaffolds were collagenized and cellularized with primary tenocytes for 7 days. Immunofluorescence staining showed a certain alignment of cell growing direction with fiber direction. In cell viability and cell proliferation assays, significant improvements in cell response were observed for the snowflake fiber and collagen coating groups, especially when combined. The data suggest that the utilization of non-circular fibers may facilitate enhanced cell guidance and surface area, while the application of a collagen coating could optimize the cellular environment for adhesion and proliferation. Full article
(This article belongs to the Special Issue Ligament/Tendon and Cartilage Tissue Engineering and Reconstruction)
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Review

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23 pages, 3434 KiB  
Review
A Narrative Review of the Roles of Chondromodulin-I (Cnmd) in Adult Cartilage Tissue
by Viviana Reyes Alcaraz, Girish Pattappa, Shigenori Miura, Peter Angele, Torsten Blunk, Maximilian Rudert, Yuji Hiraki, Chisa Shukunami and Denitsa Docheva
Int. J. Mol. Sci. 2024, 25(11), 5839; https://doi.org/10.3390/ijms25115839 - 27 May 2024
Viewed by 1563
Abstract
Articular cartilage is crucial for joint function but its avascularity limits intrinsic repair, leading to conditions like osteoarthritis (OA). Chondromodulin-I (Cnmd) has emerged as a key molecule in cartilage biology, with potential implications for OA therapy. Cnmd is primarily expressed in cartilage and [...] Read more.
Articular cartilage is crucial for joint function but its avascularity limits intrinsic repair, leading to conditions like osteoarthritis (OA). Chondromodulin-I (Cnmd) has emerged as a key molecule in cartilage biology, with potential implications for OA therapy. Cnmd is primarily expressed in cartilage and plays an important role in chondrocyte proliferation, cartilage homeostasis, and the blocking of angiogenesis. In vivo and in vitro studies on Cnmd, also suggest an involvement in bone repair and in delaying OA progression. Its downregulation correlates with OA severity, indicating its potential as a therapeutic target. Further research is needed to fully understand the mode of action of Cnmd and its beneficial implications for managing OA. This comprehensive review aims to elucidate the molecular characteristics of Cnmd, from its expression pattern, role in cartilage maintenance, callus formation during bone repair and association with OA. Full article
(This article belongs to the Special Issue Ligament/Tendon and Cartilage Tissue Engineering and Reconstruction)
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