Implantation of Various Cell-Free Matrixes Does Not Contribute to the Restoration of Hyaline Cartilage within Full-Thickness Focal Defects

Ibragimova, Shabnam; Medvedeva, Ekaterina V.; Романова, И. А.; Истранов, Л. П.; Истранова, Е. В.; Лычагин, А.В.; Nedorubov, Andrey; Timashev, P. S.; Tel’pukhov, V. I.; Chagin, Andrei S.

doi:10.3390/ijms23010292

Cited by 5 publications

(1 citation statement)

References 26 publications

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“…However, most studies on the in vivo performance of cell-free scaffolds have yielded unsatisfactory results. 22 For these reasons, the field is now focused on the development of diverse types of cell-laden constructs for cartilage repair.…”

Section: Introductionmentioning

confidence: 99%

Ex Vivo Maturation of 3D-Printed, Chondrocyte-Laden, Polycaprolactone-Based Scaffolds Prior to Transplantation Improves Engineered Cartilage Substitute Properties and Integration

et al. 2022

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Objective The surgical management of nasal septal defects due to perforations, malformations, congenital cartilage absence, traumatic defects, or tumors would benefit from availability of optimally matured septal cartilage substitutes. Here, we aimed to improve in vitro maturation of 3-dimensional (3D)-printed, cell-laden polycaprolactone (PCL)-based scaffolds and test their in vivo performance in a rabbit auricular cartilage model. Design Rabbit auricular chondrocytes were isolated, cultured, and seeded on 3D-printed PCL scaffolds. The scaffolds were cultured for 21 days in vitro under standard culture media and normoxia or in prochondrogenic and hypoxia conditions, respectively. Cell-laden scaffolds (as well as acellular controls) were implanted into perichondrium pockets of New Zealand white rabbit ears ( N = 5 per group) and followed up for 12 weeks. At study end point, the tissue-engineered scaffolds were extracted and tested by histological, immunohistochemical, mechanical, and biochemical assays. Results Scaffolds previously matured in vitro under prochondrogenic hypoxic conditions showed superior mechanical properties as well as improved patterns of cartilage matrix deposition, chondrogenic gene expression ( COL1A1, COL2A1, ACAN, SOX9, COL10A1), and proteoglycan production in vivo, compared with scaffolds cultured in standard conditions. Conclusions In vitro maturation of engineered cartilage scaffolds under prochondrogenic conditions that better mimic the in vivo environment may be beneficial to improve functional properties of the engineered grafts. The proposed maturation strategy may also be of use for other tissue-engineered constructs and may ultimately impact survival and integration of the grafts in the damaged tissue microenvironment.

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Section: Introductionmentioning

confidence: 99%

Ex Vivo Maturation of 3D-Printed, Chondrocyte-Laden, Polycaprolactone-Based Scaffolds Prior to Transplantation Improves Engineered Cartilage Substitute Properties and Integration

et al. 2022

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A Photopolymerizable Biocompatible Hyaluronic Acid Hydrogel Promotes Early Articular Cartilage Repair in a Minipig Model In Vivo

Gao,

Beninatto,

Oláh

et al. 2023

Adv Healthcare Materials

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Articular cartilage defects represent an unsolved clinical challenge. Photopolymerizable hydrogels are attractive candidates supporting repair. This study investigates the short‐term safety and efficacy of two novel hyaluronic acid (HA)‐triethylene glycol (TEG)‐coumarin hydrogels photocrosslinked in situ in a clinically relevant large animal model. We hypothesize that HA‐hydrogel‐augmented microfracture (MFX) is superior to MFX in enhancing early cartilage repair, and that the molar degree of substitution and concentration of HA affects repair. We treat chondral full‐thickness defects in the knees of adult minipigs with either (1) debridement (No MFX), (2) debridement and MFX, (3) debridement, MFX and HA hydrogel (30% molar derivatization, 30 mg/ml HA; F3) (MFX+F3), and (4) debridement, MFX and HA hydrogel (40% molar derivatization, 20 mg/ml HA; F4) (MFX+F4). After 8 weeks postoperatively, MFX+F3 significantly improves total macroscopic and histological scores compared with all other groups without negative effects, besides significantly enhancing the individual repair parameters “defect architecture”, “repair tissue surface” (compared with No MFX, MFX), and “subchondral bone” (compared with MFX). These data indicate that photopolymerizable HA hydrogels enable a favorable metastable microenvironment promoting early chondrogenesis in vivo. This work also uncovers a mechanism for effective HA‐augmented cartilage repair by combining lower molar derivatization with higher concentrations.This article is protected by copyright. All rights reserved

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Zwitterion‐Lubricated Hydrogel Microspheres Encapsulated with Metformin Ameliorate Age‐Associated Osteoarthritis

Hou,

Lin,

Zhu

et al. 2024

Advanced Science

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Chondrocyte senescence and reduced lubrication play pivotal roles in the pathogenesis of age‐related osteoarthritis (OA). In the present study, highly lubricated and drug‐loaded hydrogel microspheres are designed and fabricated through the radical polymerization of sulfobetaine (SB)‐modified hyaluronic acid methacrylate using microfluidic technology. The copolymer contains a large number of SB and carboxyl groups that can provide a high degree of lubrication through hydration and form electrostatic loading interactions with metformin (Met@SBHA), producing a high drug load for anti‐chondrocyte senescence. Mechanical, tribological, and drug release analyses demonstrated enhanced lubricative properties and prolonged drug dissemination of the Met@SBHA microspheres. RNA sequencing (RNA‐seq) analysis, network pharmacology, and in vitro assays revealed the extraordinary capacity of Met@SBHA to combat chondrocyte senescence. Additionally, inducible nitric oxide synthase (iNOS) has been identified as a promising protein modulated by Met in senescent chondrocytes, thereby exerting a significant influence on the iNOS/ONOO‐/P53 pathway. Notably, the intra‐articular administration of Met@SBHA in aged mice ameliorated cartilage senescence and OA pathogenesis. Based on the findings of this study, Met@SBHA emerges as an innovative and promising strategy in tackling age‐related OA serving the dual function of enhancing joint lubrication and mitigating cartilage senescence.

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Implantation of Various Cell-Free Matrixes Does Not Contribute to the Restoration of Hyaline Cartilage within Full-Thickness Focal Defects

Cited by 5 publications

References 26 publications

Ex Vivo Maturation of 3D-Printed, Chondrocyte-Laden, Polycaprolactone-Based Scaffolds Prior to Transplantation Improves Engineered Cartilage Substitute Properties and Integration

Ex Vivo Maturation of 3D-Printed, Chondrocyte-Laden, Polycaprolactone-Based Scaffolds Prior to Transplantation Improves Engineered Cartilage Substitute Properties and Integration

A Photopolymerizable Biocompatible Hyaluronic Acid Hydrogel Promotes Early Articular Cartilage Repair in a Minipig Model In Vivo

Zwitterion‐Lubricated Hydrogel Microspheres Encapsulated with Metformin Ameliorate Age‐Associated Osteoarthritis

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