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Strategies for Meniscus Preservation and Regeneration: From the Lab to Clinical Practice

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

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 21073

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Dr. Berardo Di Matteo

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Center for Functional and Biologic Reconstruction of the Knee, Humanitas Clinical and Research Center, Via Manzoni 113, 20089 Rozzano, Milan, Italy
Interests: cartilage; stem cells; scaffold; growth factors; TKR; CAS; orthobiology; ACL; meniscus transplant
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Dear Colleagues,

As we all know, meniscal tears are frequent in routine clinical practice and, despite increasing evidence on the necessity of preserving meniscal tissue as much as possible, arthroscopic meniscectomy is still the most common procedure in knee surgery. Although responsible for a significant post-operative improvement in pain and function, meniscectomy exposes patients to a higher risk of onset of osteoarhritis (OA). This has become even more relevant taking into account the ageing population and that this procedure is commonly performed in young patients. Therefore, meniscectomy contributes significantly to the already huge burdern of OA. Accordingly, the need for a research effort into developing alternative strategies to preserve and regenerate the meniscus becomes imperative; hence the rationale behind this special Issue entitled “Strategies for Meniscus Preservation and Regeneration: From the Lab to Clinical Practice”. We believe that the core of knee joint preservation strategies is strictly related to innovative meniscal treatments, ranging from biomaterials to biologic augmentation with cells and growth factors. This special issue will therefore accept articles focusing on pre-clinical and clinical approaches to preserve the torn menisci, or to promote their regeneration following previous resections. In-vitro and in-vivo studies are equally encouraged for submission. Moreover, we will welcome review papers or meta-analyses reporting the state of the art on the topic, in order to provide a clearer understanding of the treatment options already developed or under development, and presenting the future prospectives in this cutting edge field of regenerative medicine.

Dr. Berardo Di Matteo
Guest Editor

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Keywords

meniscus
osteoarthritis
regenerative medicine
meniscetomy
pre-clinical
scaffold
biomaterials
stem cells
growth factors

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Published Papers (6 papers)

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Editorial

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4 pages, 205 KiB

Open AccessEditorial

Navigating around the Current Options to Preserve and Regenerate Meniscus: A Long Journey Still to Be Pursued

by Berardo Di Matteo, Giuseppe Anzillotti and Elizaveta Kon

Int. J. Mol. Sci. 2022, 23(11), 6057; https://doi.org/10.3390/ijms23116057 - 27 May 2022

Cited by 3 | Viewed by 1552

Abstract

The beginning of meniscal surgery was attributed to Annadale at the end of the 19th century: interestingly, he performed the first documented surgical repair of the meniscus [...] Full article

(This article belongs to the Special Issue Strategies for Meniscus Preservation and Regeneration: From the Lab to Clinical Practice)

Research

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16 pages, 10154 KiB

Open AccessArticle

Testing Hypoxia in Pig Meniscal Culture: Biological Role of the Vascular-Related Factors in the Differentiation and Viability of Neonatal Meniscus

by Barbara Canciani, Valentina Rafaela Herrera Millar, Margherita Pallaoro, Lucia Aidos, Federica Cirillo, Luigi Anastasia, Giuseppe Maria Peretti, Silvia Clotilde Modina, Laura Mangiavini and Alessia Di Giancamillo

Int. J. Mol. Sci. 2021, 22(22), 12465; https://doi.org/10.3390/ijms222212465 - 18 Nov 2021

Cited by 8 | Viewed by 2358

Abstract

Menisci play an essential role in shock absorption, joint stability, load resistance and its transmission thanks to their conformation. Adult menisci can be divided in three zones based on the vascularization: an avascular inner zone with no blood supply, a fully vascularized outer zone, and an intermediate zone. This organization, in addition to the incomplete knowledge about meniscal biology, composition, and gene expression, makes meniscal regeneration still one of the major challenges both in orthopedics and in tissue engineering. To overcome this issue, we aimed to investigate the role of hypoxia in the differentiation of the three anatomical areas of newborn piglet menisci (anterior horn (A), central body (C), and posterior horn (P)) and its effects on vascular factors. After sample collection, menisci were divided in A, C, P, and they were cultured in vitro under hypoxic (1% O₂) and normoxic (21% O₂) conditions at four different experimental time points (T0 = day of explant; T7 = day 7; T10 = day 10; T14 = day 14); samples were then evaluated through immune, histological, and molecular analyses, cell morpho-functional characteristics; with particular focus on matrix composition and expression of vascular factors. It was observed that hypoxia retained the initial phenotype of cells and induced extracellular matrix production resembling a mature tissue. Hypoxia also modulated the expression of angiogenic factors, especially in the early phase of the study. Thus, we observed that hypoxia contributes to the fibro-chondrogenic differentiation with the involvement of angiogenic factors, especially in the posterior horn, which corresponds to the predominant weight-bearing portion. Full article

(This article belongs to the Special Issue Strategies for Meniscus Preservation and Regeneration: From the Lab to Clinical Practice)

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16 pages, 5835 KiB

Open AccessArticle

Potential of Melt Electrowritten Scaffolds Seeded with Meniscus Cells and Mesenchymal Stromal Cells

by Jasmijn V. Korpershoek, Mylène de Ruijter, Bastiaan F. Terhaard, Michella H. Hagmeijer, Daniël B.F. Saris, Miguel Castilho, Jos Malda and Lucienne A. Vonk

Int. J. Mol. Sci. 2021, 22(20), 11200; https://doi.org/10.3390/ijms222011200 - 18 Oct 2021

Cited by 9 | Viewed by 3264

Abstract

Meniscus injury and meniscectomy are strongly related to osteoarthritis, thus there is a clinical need for meniscus replacement. The purpose of this study is to create a meniscus scaffold with micro-scale circumferential and radial fibres suitable for a one-stage cell-based treatment. Poly-caprolactone-based scaffolds with three different architectures were made using melt electrowriting (MEW) technology and their in vitro performance was compared with scaffolds made using fused-deposition modelling (FDM) and with the clinically used Collagen Meniscus Implants^® (CMI^®). The scaffolds were seeded with meniscus and mesenchymal stromal cells (MSCs) in fibrin gel and cultured for 28 d. A basal level of proteoglycan production was demonstrated in MEW scaffolds, the CMI^®, and fibrin gel control, yet within the FDM scaffolds less proteoglycan production was observed. Compressive properties were assessed under uniaxial confined compression after 1 and 28 d of culture. The MEW scaffolds showed a higher Young’s modulus when compared to the CMI^® scaffolds and a higher yield point compared to FDM scaffolds. This study demonstrates the feasibility of creating a wedge-shaped meniscus scaffold with MEW using medical-grade materials and seeding the scaffold with a clinically-feasible cell number and -type for potential translation as a one-stage treatment. Full article

(This article belongs to the Special Issue Strategies for Meniscus Preservation and Regeneration: From the Lab to Clinical Practice)

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12 pages, 1530 KiB

Open AccessArticle

Detection and Evaluation of Serological Biomarkers to Predict Osteoarthritis in Anterior Cruciate Ligament Transection Combined Medial Meniscectomy Rat Model

by Nian-Cih Huang, Tsorng-Shyang Yang, Prabhakar Busa, Ching-Ling Lin, Ya-Chieh Fang, Ing-Jung Chen and Chih-Shung Wong

Int. J. Mol. Sci. 2021, 22(19), 10179; https://doi.org/10.3390/ijms221910179 - 22 Sep 2021

Cited by 5 | Viewed by 4351

Abstract

Biomarkers are essential tools in osteoarthritis (OA) research, clinical trials, and drug development. Detecting and evaluating biomarkers in OA research can open new avenues for researching and developing new therapeutics. In the present report, we have explored the serological detection of various osteoarthritis-related biomarkers in the preclinical model of OA. In this surgical OA model, we disrupted the medial tibial cartilage’s integrity via anterior cruciate ligament transection combined with medial meniscectomy (ACLT+MMx) of a single joint of Wistar rats. The progression of OA was verified, as shown by the microscopic deterioration of cartilage and the increasing cartilage degeneration scoring from 4 to 12 weeks postsurgery. The concentration of serological biomarkers was measured at two timepoints, along with the complete blood count and bone electrolytes, with biochemical analysis further conducted. The panel evaluated inflammatory biomarkers, bone/cartilage biomarkers, and lipid metabolic pathway biomarkers. In chronic OA rats, we found a significant reduction of total vitamin D3 and C-telopeptide fragments of type II (CTX-II) levels in the serum as compared to sham-operated rats. In contrast, the serological levels of adiponectin, leptin, and matrix metallopeptidase (MMP3) were significantly enhanced in chronic OA rats. The inflammatory markers, blood cell composition, and biochemical profile remained unchanged after surgery. In conclusion, we found that a preclinical model of single-joint OA with significant deterioration of the cartilage can lead to serological changes to the cartilage and metabolic-related biomarkers without alteration of the systemic blood and biochemical profile. Thus, this biomarker profile provides a new tool for diagnostic/therapeutic assessment in OA scientific research. Full article

(This article belongs to the Special Issue Strategies for Meniscus Preservation and Regeneration: From the Lab to Clinical Practice)

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16 pages, 3678 KiB

Open AccessArticle

Selection of Highly Proliferative and Multipotent Meniscus Progenitors through Differential Adhesion to Fibronectin: A Novel Approach in Meniscus Tissue Engineering

by Jasmijn V. Korpershoek, Margot Rikkers, Tommy S. de Windt, Marianna A. Tryfonidou, Daniel B. F. Saris and Lucienne A. Vonk

Int. J. Mol. Sci. 2021, 22(16), 8614; https://doi.org/10.3390/ijms22168614 - 10 Aug 2021

Cited by 7 | Viewed by 3585

Abstract

Meniscus injuries can be highly debilitating and lead to knee osteoarthritis. Progenitor cells from the meniscus could be a superior cell type for meniscus repair and tissue-engineering. The purpose of this study is to characterize meniscus progenitor cells isolated by differential adhesion to fibronectin (FN-prog). Human osteoarthritic menisci were digested, and FN-prog were selected by differential adhesion to fibronectin. Multilineage differentiation, population doubling time, colony formation, and MSC surface markers were assessed in the FN-prog and the total meniscus population (Men). Colony formation was compared between outer and inner zone meniscus digest. Chondrogenic pellet cultures were performed for redifferentiation. FN-prog demonstrated multipotency. The outer zone FN-prog formed more colonies than the inner zone FN-prog. FN-prog displayed more colony formation and a higher proliferation rate than Men. FN-prog redifferentiated in pellet culture and mostly adhered to the MSC surface marker profile, except for HLA-DR receptor expression. This is the first study that demonstrates differential adhesion to fibronectin for the isolation of a progenitor-like population from the meniscus. The high proliferation rates and ability to form meniscus extracellular matrix upon redifferentiation, together with the broad availability of osteoarthritis meniscus tissue, make FN-prog a promising cell type for clinical translation in meniscus tissue-engineering. Full article

(This article belongs to the Special Issue Strategies for Meniscus Preservation and Regeneration: From the Lab to Clinical Practice)

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Review

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15 pages, 2249 KiB

Open AccessReview

Drug Delivery Systems for the Treatment of Knee Osteoarthritis: A Systematic Review of In Vivo Studies

by Francesco Manlio Gambaro, Aldo Ummarino, Fernando Torres Andón, Flavio Ronzoni, Berardo Di Matteo and Elizaveta Kon

Int. J. Mol. Sci. 2021, 22(17), 9137; https://doi.org/10.3390/ijms22179137 - 24 Aug 2021

Cited by 26 | Viewed by 4881

Abstract

Many efforts have been made in the field of nanotechnology to improve the local and sustained release of drugs, which may be helpful to overcome the present limitations in the treatment of knee OA. Nano-/microparticles and/or hydrogels can be now engineered to improve the administration and intra-articular delivery of specific drugs, targeting molecular pathways and pathogenic mechanisms involved in OA progression and remission. In order to summarize the current state of this field, a systematic review of the literature was performed and 45 relevant studies were identified involving both animal models and humans. We found that polymeric nanoparticles loaded with anti-inflammatory drugs (i.e., dexamethasone or celecoxib) are the most frequently investigated drug delivery systems, followed by microparticles and hydrogels. In particular, the nanosystem most frequently used in preclinical research consists of PLGA-nanoparticles loaded with corticosteroids and non-steroidal anti-inflammatory drugs. Overall, improvement in histological features, reduction in joint inflammation, and improvement in clinical scores in patients were observed. The last advances in the field of nanotechnology could offer new opportunities to treat patients affected by knee OA, including those with previous meniscectomy. New smart drug delivery approaches, based on nanoparticles, microparticles, and hydrogels, may enhance the therapeutic potential of intra-articular agents by increasing the permanence of selected drugs inside the joint and better targeting specific receptors and tissues. Full article

(This article belongs to the Special Issue Strategies for Meniscus Preservation and Regeneration: From the Lab to Clinical Practice)

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