International Journal of Molecular Sciences

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16 pages, 2826 KiB

Open AccessArticle

Efficient TGF-β1 Delivery to Articular Chondrocytes In Vitro Using Agro-Based Liposomes

by Émilie Velot, Kamil Elkhoury, Cyril Kahn, Hervé Kempf, Michel Linder, Elmira Arab-Tehrany and Arnaud Bianchi

Int. J. Mol. Sci. 2022, 23(5), 2864; https://doi.org/10.3390/ijms23052864 - 5 Mar 2022

Cited by 11 | Viewed by 2348

Abstract

The low efficiency in transfecting rat- and human-derived chondrocytes have been hampering developments in the field of cartilage biology. Transforming growth factor (TGF)-β1 has shown positive effects on chondrocytes, but its applications remain limited due to its short half-life, low stability and poor [...] Read more.

The low efficiency in transfecting rat- and human-derived chondrocytes have been hampering developments in the field of cartilage biology. Transforming growth factor (TGF)-β1 has shown positive effects on chondrocytes, but its applications remain limited due to its short half-life, low stability and poor penetration into cartilage. Naturally derived liposomes have been shown to be promising delivery nanosystems due to their similarities with biological membranes. Here, we used agro-based rapeseed liposomes, which contains a high level of mono- and poly-unsaturated fatty acids, to efficiently deliver encapsulated TGF-β1 to rat chondrocytes. Results showed that TGF-β1 encapsulated in nano-sized rapeseed liposomes were safe for chondrocytes and did not induce any alterations of their phenotype. Furthermore, the controlled release of TGF-β1 from liposomes produced an improved response in chondrocytes, even at low doses. Altogether, these outcomes demonstrate that agro-based nanoliposomes are promising drug carriers. Full article

(This article belongs to the Special Issue Molecular and Tissue Engineering Approaches in Musculoskeletal Regenerative Medicine 3.0)

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18 pages, 2653 KiB

Open AccessArticle

Development of a Gene-Activated Scaffold Incorporating Multifunctional Cell-Penetrating Peptides for pSDF-1α Delivery for Enhanced Angiogenesis in Tissue Engineering Applications

by Rachael N. Power, Brenton L. Cavanagh, James E. Dixon, Caroline M. Curtin and Fergal J. O’Brien

Int. J. Mol. Sci. 2022, 23(3), 1460; https://doi.org/10.3390/ijms23031460 - 27 Jan 2022

Cited by 23 | Viewed by 4268

Abstract

Non-viral gene delivery has become a popular approach in tissue engineering, as it permits the transient delivery of a therapeutic gene, in order to stimulate tissue repair. However, the efficacy of non-viral delivery vectors remains an issue. Our lab has created gene-activated scaffolds [...] Read more.

Non-viral gene delivery has become a popular approach in tissue engineering, as it permits the transient delivery of a therapeutic gene, in order to stimulate tissue repair. However, the efficacy of non-viral delivery vectors remains an issue. Our lab has created gene-activated scaffolds by incorporating various non-viral delivery vectors, including the glycosaminoglycan-binding enhanced transduction (GET) peptide into collagen-based scaffolds with proven osteogenic potential. A modification to the GET peptide (FLR) by substitution of arginine residues with histidine (FLH) has been designed to enhance plasmid DNA (pDNA) delivery. In this study, we complexed pDNA with combinations of FLR and FLH peptides, termed GET* nanoparticles. We sought to enhance our gene-activated scaffold platform by incorporating GET* nanoparticles into collagen–nanohydroxyapatite scaffolds with proven osteogenic capacity. GET* N/P 8 was shown to be the most effective formulation for delivery to MSCs in 2D. Furthermore, GET* N/P 8 nanoparticles incorporated into collagen–nanohydroxyapatite (coll–nHA) scaffolds at a 1:1 ratio of collagen:nanohydroxyapatite was shown to be the optimal gene-activated scaffold. pDNA encoding stromal-derived factor 1α (pSDF-1α), an angiogenic chemokine which plays a role in BMP mediated differentiation of MSCs, was then delivered to MSCs using our optimised gene-activated scaffold platform, with the aim of significantly increasing angiogenesis as an important precursor to bone repair. The GET* N/P 8 coll–nHA scaffolds successfully delivered pSDF-1α to MSCs, resulting in a significant, sustained increase in SDF-1α protein production and an enhanced angiogenic effect, a key precursor in the early stages of bone repair. Full article

(This article belongs to the Special Issue Molecular and Tissue Engineering Approaches in Musculoskeletal Regenerative Medicine 3.0)

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20 pages, 7540 KiB

Open AccessArticle

Tethered TGF-β1 in a Hyaluronic Acid-Based Bioink for Bioprinting Cartilaginous Tissues

by Julia Hauptstein, Leonard Forster, Ali Nadernezhad, Jürgen Groll, Jörg Teßmar and Torsten Blunk

Int. J. Mol. Sci. 2022, 23(2), 924; https://doi.org/10.3390/ijms23020924 - 15 Jan 2022

Cited by 30 | Viewed by 4007

Abstract

In 3D bioprinting for cartilage regeneration, bioinks that support chondrogenic development are of key importance. Growth factors covalently bound in non-printable hydrogels have been shown to effectively promote chondrogenesis. However, studies that investigate the functionality of tethered growth factors within 3D printable bioinks [...] Read more.

In 3D bioprinting for cartilage regeneration, bioinks that support chondrogenic development are of key importance. Growth factors covalently bound in non-printable hydrogels have been shown to effectively promote chondrogenesis. However, studies that investigate the functionality of tethered growth factors within 3D printable bioinks are still lacking. Therefore, in this study, we established a dual-stage crosslinked hyaluronic acid-based bioink that enabled covalent tethering of transforming growth factor-beta 1 (TGF-β1). Bone marrow-derived mesenchymal stromal cells (MSCs) were cultured over three weeks in vitro, and chondrogenic differentiation of MSCs within bioink constructs with tethered TGF-β1 was markedly enhanced, as compared to constructs with non-covalently incorporated TGF-β1. This was substantiated with regard to early TGF-β1 signaling, chondrogenic gene expression, qualitative and quantitative ECM deposition and distribution, and resulting construct stiffness. Furthermore, it was successfully demonstrated, in a comparative analysis of cast and printed bioinks, that covalently tethered TGF-β1 maintained its functionality after 3D printing. Taken together, the presented ink composition enabled the generation of high-quality cartilaginous tissues without the need for continuous exogenous growth factor supply and, thus, bears great potential for future investigation towards cartilage regeneration. Furthermore, growth factor tethering within bioinks, potentially leading to superior tissue development, may also be explored for other biofabrication applications. Full article

(This article belongs to the Special Issue Molecular and Tissue Engineering Approaches in Musculoskeletal Regenerative Medicine 3.0)

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15 pages, 3542 KiB

Open AccessArticle

An In Vitro Evaluation of the Biological and Osteogenic Properties of Magnesium-Doped Bioactive Glasses for Application in Bone Tissue Engineering

by Frederike Hohenbild, Marcela Arango Ospina, Sarah I. Schmitz, Arash Moghaddam, Aldo R. Boccaccini and Fabian Westhauser

Int. J. Mol. Sci. 2021, 22(23), 12703; https://doi.org/10.3390/ijms222312703 - 24 Nov 2021

Cited by 22 | Viewed by 2871

Abstract

Magnesium (Mg²⁺) is known to play a crucial role in mineral and matrix metabolism of bone tissue and is thus increasingly considered in the field of bone tissue engineering. Bioactive glasses (BGs) offer the promising possibility of the incorporation and local [...] Read more.

Magnesium (Mg²⁺) is known to play a crucial role in mineral and matrix metabolism of bone tissue and is thus increasingly considered in the field of bone tissue engineering. Bioactive glasses (BGs) offer the promising possibility of the incorporation and local delivery of therapeutically active ions as Mg²⁺. In this study, two Mg²⁺-doped derivatives of the ICIE16-BG composition (49.46 SiO₂, 36.27 CaO, 6.6 Na₂O, 1.07 P₂O₅, 6.6 K₂O (mol%)), namely 6Mg-BG (49.46 SiO₂, 30.27 CaO, 6.6 Na₂O, 1.07 P₂O₅, 6.6 K₂O, 6.0 MgO (mol%) and 3Mg-BG (49.46 SiO₂, 33.27 CaO, 6.6 Na₂O, 1.07 P₂O₅, 6.6 K₂O, 3.0 MgO (mol%)) were examined. Their influence on viability, proliferation and osteogenic differentiation of human mesenchymal stromal cells (MSCs) was explored in comparison to the original ICIE16-BG. All BGs showed good biocompatibility. The Mg²⁺-doped BGs had a positive influence on MSC viability alongside with inhibiting effects on MSC proliferation. A strong induction of osteogenic differentiation markers was observed, with the Mg²⁺-doped BGs significantly outperforming the ICIE16-BG regarding the expression of genes encoding for protein members of the osseous extracellular matrix (ECM) at certain observation time points. However, an overall Mg²⁺-induced enhancement of the expression of genes encoding for ECM proteins could not be observed, possibly due to a too moderate Mg²⁺ release. By adaption of the Mg²⁺ release from BGs, an even stronger impact on the expression of genes encoding for ECM proteins might be achieved. Furthermore, other BG-types such as mesoporous BGs might provide a higher local presence of the therapeutically active ions and should therefore be considered for upcoming studies. Full article

(This article belongs to the Special Issue Molecular and Tissue Engineering Approaches in Musculoskeletal Regenerative Medicine 3.0)

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23 pages, 3433 KiB

Open AccessArticle

Novel Chitosan-Silica Hybrid Hydrogels for Cell Encapsulation and Drug Delivery

by Soher N. Jayash, Paul R. Cooper, Richard M. Shelton, Sarah A. Kuehne and Gowsihan Poologasundarampillai

Int. J. Mol. Sci. 2021, 22(22), 12267; https://doi.org/10.3390/ijms222212267 - 12 Nov 2021

Cited by 20 | Viewed by 3401

Abstract

Hydrogels constructed from naturally derived polymers provide an aqueous environment that encourages cell growth, however, mechanical properties are poor and degradation can be difficult to predict. Whilst, synthetic hydrogels exhibit some improved mechanical properties, these materials lack biochemical cues for cells growing and [...] Read more.

Hydrogels constructed from naturally derived polymers provide an aqueous environment that encourages cell growth, however, mechanical properties are poor and degradation can be difficult to predict. Whilst, synthetic hydrogels exhibit some improved mechanical properties, these materials lack biochemical cues for cells growing and have limited biodegradation. To produce hydrogels that support 3D cell cultures to form tissue mimics, materials must exhibit appropriate biological and mechanical properties. In this study, novel organic-inorganic hybrid hydrogels based on chitosan and silica were prepared using the sol-gel technique. The chemical, physical and biological properties of the hydrogels were assessed. Statistical analysis was performed using One-Way ANOVAs and independent-sample t-tests. Fourier transform infrared spectroscopy showed characteristic absorption bands including amide II, Si-O and Si-O-Si confirming formation of hybrid networks. Oscillatory rheometry was used to characterise the sol to gel transition and viscoelastic behaviour of hydrogels. Furthermore, in vitro degradation revealed both chitosan and silica were released over 21 days. The hydrogels exhibited high loading efficiency as total protein loading was released in a week. There were significant differences between TC₂G and C₂G at all-time points (p < 0.05). The viability of osteoblasts seeded on, and encapsulated within, the hydrogels was >70% over 168 h culture and antimicrobial activity was demonstrated against Pseudomonas aeruginosa and Enterococcus faecalis. The hydrogels developed here offer alternatives for biopolymer hydrogels for biomedical use, including for application in drug/cell delivery and for bone tissue engineering. Full article

(This article belongs to the Special Issue Molecular and Tissue Engineering Approaches in Musculoskeletal Regenerative Medicine 3.0)

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13 pages, 8714 KiB

Open AccessArticle

Enhancing the Efficiency of Distraction Osteogenesis through Rate-Varying Distraction: A Computational Study

by Ruisen Fu, Yili Feng, David Bertrand, Tianming Du, Youjun Liu, Bettina M. Willie and Haisheng Yang

Int. J. Mol. Sci. 2021, 22(21), 11734; https://doi.org/10.3390/ijms222111734 - 29 Oct 2021

Cited by 8 | Viewed by 2346

Abstract

Distraction osteogenesis (DO) is a mechanobiological process of producing new bone and overlying soft tissues through the gradual and controlled distraction of surgically separated bone segments. The process of bone regeneration during DO is largely affected by distraction parameters. In the present study, [...] Read more.

Distraction osteogenesis (DO) is a mechanobiological process of producing new bone and overlying soft tissues through the gradual and controlled distraction of surgically separated bone segments. The process of bone regeneration during DO is largely affected by distraction parameters. In the present study, a distraction strategy with varying distraction rates (i.e., “rate-varying distraction”) is proposed, with the aim of shortening the distraction time and improving the efficiency of DO. We hypothesized that faster and better healing can be achieved with rate-varying distractions, as compared with constant-rate distractions. A computational model incorporating the viscoelastic behaviors of the callus tissues and the mechano-regulatory tissue differentiation laws was developed and validated to predict the bone regeneration process during DO. The effect of rate-varying distraction on the healing outcomes (bony bridging time and bone formation) was examined. Compared to the constant low-rate distraction, a low-to-high rate-varying distraction provided a favorable mechanical environment for angiogenesis and bone tissue differentiation, throughout the distraction and consolidation phase, leading to an improved healing outcome with a shortened healing time. These results suggest that a rate-varying clinical strategy could reduce the overall treatment time of DO and decrease the risk of complications related to the external fixator. Full article

(This article belongs to the Special Issue Molecular and Tissue Engineering Approaches in Musculoskeletal Regenerative Medicine 3.0)

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18 pages, 3175 KiB

Open AccessArticle

Altered Secretome of Diabetic Monocytes Could Negatively Influence Fracture Healing—An In Vitro Study

by Caren Linnemann, Lorena Savini, Mika F. Rollmann, Tina Histing, Andreas K. Nussler and Sabrina Ehnert

Int. J. Mol. Sci. 2021, 22(17), 9212; https://doi.org/10.3390/ijms22179212 - 26 Aug 2021

Cited by 6 | Viewed by 2469

Abstract

Diabetes mellitus is a main risk factor for delayed fracture healing and fracture non-unions. Successful fracture healing requires stimuli from different immune cells, known to be affected in diabetics. Especially, application of mononuclear cells has been proposed to promote wound and fracture healing. [...] Read more.

Diabetes mellitus is a main risk factor for delayed fracture healing and fracture non-unions. Successful fracture healing requires stimuli from different immune cells, known to be affected in diabetics. Especially, application of mononuclear cells has been proposed to promote wound and fracture healing. Thus, aim was to investigate the effect of pre-/diabetic conditions on mononuclear cell functions essential to promote osteoprogenitor cell function. We here show that pre-/diabetic conditions suppress the expression of chemokines, e.g., CCL2 and CCL8 in osteoprogenitor cells. The associated MCP-1 and MCP-2 were significantly reduced in serum of diabetics. Both MCPs chemoattract mononuclear THP-1 cells. Migration of these cells is suppressed under hyperglycemic conditions, proposing that less mononuclear cells invade the site of fracture in diabetics. Further, we show that the composition of cytokines secreted by mononuclear cells strongly differ between diabetics and controls. Similar is seen in THP-1 cells cultured under hyperinsulinemia or hyperglycemia. The altered secretome reduces the positive effect of the THP-1 cell conditioned medium on migration of osteoprogenitor cells. In summary, our data support that factors secreted by mononuclear cells may support fracture healing by promoting migration of osteoprogenitor cells but suggest that this effect might be reduced in diabetics. Full article

(This article belongs to the Special Issue Molecular and Tissue Engineering Approaches in Musculoskeletal Regenerative Medicine 3.0)

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27 pages, 3453 KiB

Open AccessArticle

Tumor Suppressive Role of miR-342-5p in Human Chondrosarcoma Cells and 3D Organoids

by Clément Veys, Abderrahim Benmoussa, Romain Contentin, Amandine Duchemin, Emilie Brotin, Jérôme E. Lafont, Yannick Saintigny, Laurent Poulain, Christophe Denoyelle, Magali Demoor, Florence Legendre and Philippe Galéra

Int. J. Mol. Sci. 2021, 22(11), 5590; https://doi.org/10.3390/ijms22115590 - 25 May 2021

Cited by 14 | Viewed by 3995

Abstract

Chondrosarcomas are malignant bone tumors. Their abundant cartilage-like extracellular matrix and their hypoxic microenvironment contribute to their resistance to chemotherapy and radiotherapy, and no effective therapy is currently available. MicroRNAs (miRNAs) may be an interesting alternative in the development of therapeutic options. Here, [...] Read more.

Chondrosarcomas are malignant bone tumors. Their abundant cartilage-like extracellular matrix and their hypoxic microenvironment contribute to their resistance to chemotherapy and radiotherapy, and no effective therapy is currently available. MicroRNAs (miRNAs) may be an interesting alternative in the development of therapeutic options. Here, for the first time in chondrosarcoma cells, we carried out high-throughput functional screening using impedancemetry, and identified five miRNAs with potential antiproliferative or chemosensitive effects on SW1353 chondrosarcoma cells. The cytotoxic effects of miR-342-5p and miR-491-5p were confirmed on three chondrosarcoma cell lines, using functional validation under normoxia and hypoxia. Both miRNAs induced apoptosis and miR-342-5p also induced autophagy. Western blots and luciferase reporter assays identified for the first time Bcl-2 as a direct target of miR-342-5p, and also Bcl-xL as a direct target of both miR-342-5p and miR-491-5p in chondrosarcoma cells. MiR-491-5p also inhibited EGFR expression. Finally, only miR-342-5p induced cell death on a relevant 3D chondrosarcoma organoid model under hypoxia that mimics the in vivo microenvironment. Altogether, our results revealed the tumor suppressive activity of miR-342-5p, and to a lesser extent of miR-491-5p, on chondrosarcoma lines. Through this study, we also confirmed the potential of Bcl-2 family members as therapeutic targets in chondrosarcomas. Full article

(This article belongs to the Special Issue Molecular and Tissue Engineering Approaches in Musculoskeletal Regenerative Medicine 3.0)

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16 pages, 3808 KiB

Open AccessArticle

Dexamethasone Induces Changes in Osteogenic Differentiation of Human Mesenchymal Stromal Cells via SOX9 and PPARG, but Not RUNX2

by Elena Della Bella, Antoine Buetti-Dinh, Ginevra Licandro, Paras Ahmad, Valentina Basoli, Mauro Alini and Martin J. Stoddart

Int. J. Mol. Sci. 2021, 22(9), 4785; https://doi.org/10.3390/ijms22094785 - 30 Apr 2021

Cited by 20 | Viewed by 4905

Abstract

Despite the huge body of research on osteogenic differentiation and bone tissue engineering, the translation potential of in vitro results still does not match the effort employed. One reason might be that the protocols used for in vitro research have inherent pitfalls. The [...] Read more.

Despite the huge body of research on osteogenic differentiation and bone tissue engineering, the translation potential of in vitro results still does not match the effort employed. One reason might be that the protocols used for in vitro research have inherent pitfalls. The synthetic glucocorticoid dexamethasone is commonly used in protocols for trilineage differentiation of human bone marrow mesenchymal stromal cells (hBMSCs). However, in the case of osteogenic commitment, dexamethasone has the main pitfall of inhibiting terminal osteoblast differentiation, and its pro-adipogenic effect is well known. In this work, we aimed to clarify the role of dexamethasone in the osteogenesis of hBMSCs, with a particular focus on off-target differentiation. The results showed that dexamethasone does induce osteogenic differentiation by inhibiting SOX9 expression, but not directly through RUNX2 upregulation as it is commonly thought. Rather, PPARG is concomitantly and strongly upregulated, leading to the formation of adipocyte-like cells within osteogenic cultures. Limiting the exposure to dexamethasone to the first week of differentiation did not affect the mineralization potential. Gene expression levels of RUNX2, SOX9, and PPARG were simulated using approximate Bayesian computation based on a simplified theoretical model, which was able to reproduce the observed experimental trends but with a different range of responses, indicating that other factors should be integrated to fully understand how dexamethasone influences cell fate. In summary, this work provides evidence that current in vitro differentiation protocols based on dexamethasone do not represent a good model, and further research is warranted in this field. Full article

(This article belongs to the Special Issue Molecular and Tissue Engineering Approaches in Musculoskeletal Regenerative Medicine 3.0)

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13 pages, 11239 KiB

Open AccessArticle

Complement Regulation in Human Tenocytes under the Influence of Anaphylatoxin C5a

by Sandeep Silawal, Benjamin Kohl, Jingjian Shi and Gundula Schulze-Tanzil

Int. J. Mol. Sci. 2021, 22(6), 3105; https://doi.org/10.3390/ijms22063105 - 18 Mar 2021

Cited by 2 | Viewed by 4093

Abstract

A central part of the complement system, the anaphylatoxin C5a was investigated in this study to learn its effects on tenocytes in respect to understanding the potential expression of other crucial complement factors and pro-inflammatory mediators involved in tendinopathy. Human hamstring tendon-derived tenocytes [...] Read more.

A central part of the complement system, the anaphylatoxin C5a was investigated in this study to learn its effects on tenocytes in respect to understanding the potential expression of other crucial complement factors and pro-inflammatory mediators involved in tendinopathy. Human hamstring tendon-derived tenocytes were treated with recombinant C5a protein in concentrations of 25 ng/mL and 100 ng/mL for 0.5 h (early phase), 4 h (intermediate phase), and 24 h (late phase). Tenocytes survival was assessed after 24 h stimulation by live-dead assay. The gene expression of complement-related factors C5aR, the complement regulatory proteins (CRPs) CD46, CD55, CD59, and of the pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 was monitored using qPCR. Tenocytes were immunolabeled for C5aR and CD55 proteins. TNFα production was monitored by ELISA. Tenocyte survival was not impaired through C5a stimulation. Interestingly, the gene expression of C5aR and that of the CRPs CD46 and CD59 was significantly reduced in the intermediate and late phase, and that of TNFα only in an early phase, compared to the control group. ELISA analysis indicated a concomitant not significant trend of impaired TNFα protein synthesis at 4 h. However, there was also an early significant induction of CD55 and CD59 mediated by 25 ng/mL anaphylatoxin C5a. Hence, exposure of tenocytes to C5a obviously evokes a time and concentration-dependent response in their expression of complement and pro-inflammatory factors. C5a, released in damaged tendons, might directly contribute to tenocyte activation and thereby be involved in tendon healing and tendinopathy. Full article

(This article belongs to the Special Issue Molecular and Tissue Engineering Approaches in Musculoskeletal Regenerative Medicine 3.0)

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Review

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10 pages, 586 KiB

Open AccessReview

Clinical Application of Adipose Derived Stem Cells for the Treatment of Aseptic Non-Unions: Current Stage and Future Perspectives—Systematic Review

by Amarildo Smakaj, Domenico De Mauro, Giuseppe Rovere, Silvia Pietramala, Giulio Maccauro, Ornella Parolini, Wanda Lattanzi and Francesco Liuzza

Int. J. Mol. Sci. 2022, 23(6), 3057; https://doi.org/10.3390/ijms23063057 - 11 Mar 2022

Cited by 18 | Viewed by 3640

Abstract

Fracture non-union is a challenging orthopaedic issue and a socio-economic global burden. Several biological therapies have been introduced to improve traditional surgical approaches. Among these, the latest research has been focusing on adipose tissue as a powerful source of mesenchymal stromal cells, namely, [...] Read more.

Fracture non-union is a challenging orthopaedic issue and a socio-economic global burden. Several biological therapies have been introduced to improve traditional surgical approaches. Among these, the latest research has been focusing on adipose tissue as a powerful source of mesenchymal stromal cells, namely, adipose-derived stem cells (ADSCs). ADSC are commonly isolated from the stromal vascular fraction (SVF) of liposuctioned hypodermal adipose tissue, and their applications have been widely investigated in many fields, including non-union fractures among musculoskeletal disorders. This review aims at providing a comprehensive update of the literature on clinical application of ADSCs for the treatment of non-unions in humans. The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Only three articles met our inclusion criteria, with a total of 12 cases analyzed for demographics and harvesting, potential manufacturing and implantation of ADSCs. The review of the literature suggests that adipose derived cell therapy can represent a promising alternative in bone regenerative medicine for the enhancement of non-unions and bone defects. The low number of manuscripts reporting ADSC-based therapies for long bone fracture healing suggests some critical issues that are discussed in this review. Nevertheless, further investigations on human ADSC therapies are needed to improve the knowledge on their translational potential and to possibly achieve a consensus on their use for such applications. Full article

(This article belongs to the Special Issue Molecular and Tissue Engineering Approaches in Musculoskeletal Regenerative Medicine 3.0)

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11 pages, 1605 KiB

Open AccessReview

Mitochondrial Genome Editing to Treat Human Osteoarthritis—A Narrative Review

by Gang Zhong, Henning Madry and Magali Cucchiarini

Int. J. Mol. Sci. 2022, 23(3), 1467; https://doi.org/10.3390/ijms23031467 - 27 Jan 2022

Cited by 8 | Viewed by 4132

Abstract

Osteoarthritis (OA) is a severe, common chronic orthopaedic disorder characterised by a degradation of the articular cartilage with an incidence that increases over years. Despite the availability of various clinical options, none can stop the irreversible progression of the disease to definitely cure [...] Read more.

Osteoarthritis (OA) is a severe, common chronic orthopaedic disorder characterised by a degradation of the articular cartilage with an incidence that increases over years. Despite the availability of various clinical options, none can stop the irreversible progression of the disease to definitely cure OA. Various mutations have been evidenced in the mitochondrial DNA (mtDNA) of cartilage cells (chondrocytes) in OA, leading to a dysfunction of the mitochondrial oxidative phosphorylation processes that significantly contributes to OA cartilage degeneration. The mitochondrial genome, therefore, represents a central, attractive target for therapy in OA, especially using genome editing procedures. In this narrative review article, we present and discuss the current advances and breakthroughs in mitochondrial genome editing as a potential, novel treatment to overcome mtDNA-related disorders such as OA. While still in its infancy and despite a number of challenges that need to be addressed (barriers to effective and site-specific mtDNA editing and repair), such a strategy has strong value to treat human OA in the future, especially using the groundbreaking clustered regularly interspaced short palindromic repeats (CRIPSR)/CRISPR-associated 9 (CRISPR/Cas9) technology and mitochondrial transplantation approaches. Full article

(This article belongs to the Special Issue Molecular and Tissue Engineering Approaches in Musculoskeletal Regenerative Medicine 3.0)

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42 pages, 5767 KiB

Open AccessReview

Application of Alginate Hydrogels for Next-Generation Articular Cartilage Regeneration

by Wei Liu, Henning Madry and Magali Cucchiarini

Int. J. Mol. Sci. 2022, 23(3), 1147; https://doi.org/10.3390/ijms23031147 - 20 Jan 2022

Cited by 57 | Viewed by 5392

Abstract

The articular cartilage has insufficient intrinsic healing abilities, and articular cartilage injuries often progress to osteoarthritis. Alginate-based scaffolds are attractive biomaterials for cartilage repair and regeneration, allowing for the delivery of cells and therapeutic drugs and gene sequences. In light of the heterogeneity [...] Read more.

The articular cartilage has insufficient intrinsic healing abilities, and articular cartilage injuries often progress to osteoarthritis. Alginate-based scaffolds are attractive biomaterials for cartilage repair and regeneration, allowing for the delivery of cells and therapeutic drugs and gene sequences. In light of the heterogeneity of findings reporting the benefits of using alginate for cartilage regeneration, a better understanding of alginate-based systems is needed in order to improve the approaches aiming to enhance cartilage regeneration with this compound. This review provides an in-depth evaluation of the literature, focusing on the manipulation of alginate as a tool to support the processes involved in cartilage healing in order to demonstrate how such a material, used as a direct compound or combined with cell and gene therapy and with scaffold-guided gene transfer procedures, may assist cartilage regeneration in an optimal manner for future applications in patients. Full article

(This article belongs to the Special Issue Molecular and Tissue Engineering Approaches in Musculoskeletal Regenerative Medicine 3.0)

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28 pages, 2126 KiB

Open AccessReview

Role of the Myokine Irisin on Bone Homeostasis: Review of the Current Evidence

by Amanda Kornel, Danja J. Den Hartogh, Panagiota Klentrou and Evangelia Tsiani

Int. J. Mol. Sci. 2021, 22(17), 9136; https://doi.org/10.3390/ijms22179136 - 24 Aug 2021

Cited by 24 | Viewed by 3976

Abstract

Bone is a highly dynamic tissue that is constantly adapting to micro-changes to facilitate movement. When the balance between bone building and resorption shifts more towards bone resorption, the result is reduced bone density and mineralization, as seen in osteoporosis or osteopenia. Current [...] Read more.

Bone is a highly dynamic tissue that is constantly adapting to micro-changes to facilitate movement. When the balance between bone building and resorption shifts more towards bone resorption, the result is reduced bone density and mineralization, as seen in osteoporosis or osteopenia. Current treatment strategies aimed to improve bone homeostasis and turnover are lacking in efficacy, resulting in the search for new preventative and nutraceutical treatment options. The myokine irisin, since its discovery in 2012, has been shown to play an important role in many tissues including muscle, adipose, and bone. Evidence indicate that irisin is associated with increased bone formation and decreased bone resorption, leading to reduced risk of osteoporosis in post-menopausal women. In addition, low serum irisin levels have been found in individuals with osteoporosis and osteopenia. Irisin targets key signaling proteins, promoting osteoblastogenesis and reducing osteoclastogenesis. The present review summarizes the existing evidence regarding the effects of irisin on bone homeostasis. Full article

(This article belongs to the Special Issue Molecular and Tissue Engineering Approaches in Musculoskeletal Regenerative Medicine 3.0)

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21 pages, 11333 KiB

Open AccessReview

Nanomaterials for the Diagnosis and Treatment of Inflammatory Arthritis

by Seyedeh Maryam Hosseinikhah, Mahmood Barani, Abbas Rahdar, Henning Madry, Rabia Arshad, Vahideh Mohammadzadeh and Magali Cucchiarini

Int. J. Mol. Sci. 2021, 22(6), 3092; https://doi.org/10.3390/ijms22063092 - 18 Mar 2021

Cited by 37 | Viewed by 5595

Abstract

Nanomaterials have received increasing attention due to their unique chemical and physical properties for the treatment of rheumatoid arthritis (RA), the most common complex multifactorial joint-associated autoimmune inflammatory disorder. RA is characterized by an inflammation of the synovium with increased production of proinflammatory [...] Read more.

Nanomaterials have received increasing attention due to their unique chemical and physical properties for the treatment of rheumatoid arthritis (RA), the most common complex multifactorial joint-associated autoimmune inflammatory disorder. RA is characterized by an inflammation of the synovium with increased production of proinflammatory cytokines (IL-1, IL-6, IL-8, and IL-10) and by the destruction of the articular cartilage and bone, and it is associated with the development of cardiovascular disorders such as heart attack and stroke. While a number of imaging tools allow for the monitoring and diagnosis of inflammatory arthritis, and despite ongoing work to enhance their sensitivity and precision, the proper assessment of RA remains difficult particularly in the early stages of the disease. Our goal here is to describe the benefits of applying various nanomaterials as next-generation RA imaging and detection tools using contrast agents and nanosensors and as improved drug delivery systems for the effective treatment of the disease. Full article

(This article belongs to the Special Issue Molecular and Tissue Engineering Approaches in Musculoskeletal Regenerative Medicine 3.0)

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