An injectable continuous stratified structurally and functionally biomimetic construct for enhancing osteochondral regeneration

Zhu, Yimeng; Kong, Liang; Farhadi, Fatemeh; Xia, Wei; Chang, Jiang; He, Yaohua; Li, Haiyan

doi:10.1016/j.biomaterials.2018.11.017

Cited by 124 publications

(101 citation statements)

References 40 publications

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“…Underlying mechanism of hUC-MSCs-sEVs on cartilage regeneration. [8,44], which was conducive to the synthesis of hyaline cartilage. Herein, we found that hUC-MSCs-sEVs enhanced the migration, proliferation and chondrogenic differentiation of hBMSCs.…”

Section: Discussionmentioning

confidence: 99%

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miR‐23a‐3p‐abundant small extracellular vesicles released from Gelma/nanoclay hydrogel for cartilage regeneration

Dong

et al. 2020

J of Extracellular Vesicle

201

187

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Articular cartilage has limited self-regenerative capacity and the therapeutic methods for cartilage defects are still dissatisfactory in clinic. Recent studies showed that exosomes derived from mesenchymal stem cells promoted chondrogenesis by delivering bioactive substances to the recipient cells, indicating exosomes might be a novel method for repairing cartilage defect. Herein, we investigated the role and mechanism of human umbilical cord mesenchymal stem cells derived small extracellular vesicles (hUC-MSCs-sEVs) on cartilage regeneration. In vitro results showed that hUC-MSCs-sEVs promoted the migration, proliferation and differentiation of chondrocytes and human bone marrow mesenchymal stem cells (hBMSCs). MiRNA microarray showed that miR-23a-3p was the most highly expressed among the various miRNAs contained in hUC-MSCs-sEVs. Our data revealed that hUC-MSCs-sEVs promoted cartilage regeneration by transferring miR-23a-3p to suppress the level of PTEN and elevate expression of AKT. Moreover, we fabricated Gelatin methacrylate (Gelma)/nanoclay hydrogel (Gel-nano) for sustained release of sEVs, which was biocompatible and exhibited excellent mechanical property. In vivo results showed that hUC-MSCs-sEVs containing Gelma/nanoclay hydrogel (Gel-nano-sEVs) effectively promoted cartilage regeneration. These results indicated that Gel-nano-sEVs have a promising capacity to stimulate chondrogenesis and heal cartilage defects, and also provided valuable data for understanding the role and mechanism of hUC-MSCs-sEVs in cartilage regeneration.

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Section: Discussionmentioning

confidence: 99%

“…Mesenchymal stem cells (MSCs)-based tissue engineering has promising potential therapy for cartilage defects [ 6 – 8 ]. Human umbilical cord MSCs (hUC-MSCs) possess desirable biological properties, such as abundant tissue source, great expansion capability and painless collection process [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

miR‐23a‐3p‐abundant small extracellular vesicles released from Gelma/nanoclay hydrogel for cartilage regeneration

Dong

et al. 2020

J of Extracellular Vesicle

201

187

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“…Furthermore, in the case of laminate composites, the weak strength bonding between layers normally results in phase separation, not leading to tissue regeneration. Therefore, some reports focused on the use of single scaffolds for osteochondral regeneration [15,16]. These scaffolds ensure continuity between phases to avoid a barrier in the interface, together with biomaterials integrity, while mimicking the natural hierarchical structure of the osteochondral tissue.…”

Section: A Multifactorial Toolbox For Designing Tissue Engineering Stmentioning

confidence: 99%

A Physiology-Inspired Multifactorial Toolbox in Soft-to-Hard Musculoskeletal Interface Tissue Engineering

Calejo

Costa‐Almeida

Reis

et al. 2020

Trends in Biotechnology

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“…Previous studies have reported when gel rigidity increased, although overall cell survival decreased, more osteogenic differentiation of MSCs was observed [28] . Some researchers have reported that BMSCs showed osteogenic differentiation in the bioglass-alginate scaffold with strong mechanical properties [29]. Some studies have demonstrated that BMSCs cultured in calcium phosphate scaffolds embedded in CS hydrogels increase cartilage matrix components synthesis and chondrogenic diffrentiation, in comparison to calcium phosphate scaffolds alone [30].…”

Section: Discussionmentioning

confidence: 99%

Efficacy of a Thermally Triggered Injectable Hydrogel CS/Col /PLA/GP and BMSCs for Cartilage Tissue Engineering

2020

Preprint

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BackgroundArticular cartilage has limited self-repair ability. Tissue engineering is considered to be one of the most promising therapeutic approaches. Chitosan (CS) based hydrogels are the most widely used scaffolds which still need improvement. The purpose of this study was to investigate the efficacy of a thermally triggered injectable chitosan / type II collagen / polylactic acid / sodium β-glycerophosphate (CS/Col/PLA/GP) hydrogel and bone marrow mesenchymal stem cells (BMSCs) for the treatment of cartilage defects in rabbit knee joints. Material/MethodsThe CS-based hydrogels consisting of CS, Col II, PLA and GP were fabricated by chemical cross-linking method. The gel forming time and elastic modulus of these hydrogels were measured. We tested the viability, proliferation and differentiation of rabbit BMSCs cultured in the hydrogels by fluorescence staining, CCK-8 and PCR method. The hydrogels combined with or without BMSCs were injected into cartilage defects in rabbit knee joints and the materials were collected at 8 weeks after surgery. The repair effect of cartilage defects was evaluated based on gross observation, HE, safranin O and immunohistochemical staining. ResultsThe CS/Col/PLA/GP hydrogel was liquid at room temperature and gelled after 7.5±0.41min at 37°C. CS/Col /PLA/GP hydrogel had a modulus of 8.90 ± 0.12 kPa while CS/GP and CS/Col/GP hydrogels had the modulus of 4.07 ± 0.24 kPa and 4.93 ± 0.09 kPa. The results of Live/Dead cell viability assay reveal that most of BMSCs remained alive in the hydrogels. CCK-8 assay shows that the number of cells in CS/Col /PLA/GP hydrogel was significantly higher in comparison to the other groups on days 2 and 3 of cell culture (p<0.05). Aggrecan mRNA expression in the CS/Col /PLA/GP gel was the highest (p<0.05). Sox9 mRNA expression in the CS/Col /GP group was the highest, in which CS/Col /PLA/GP hydrogel was higher than the CS/GP hydrogel(p<0.05). Furthermore, CS/Col/PLA/GP and CS/Col /GP hydrogels showed higher COL2A1 mRNA expression in comparison to CS/GP constructs (p<0.05). In vivo studies showed that approximately 90% of the cartilage defects of rabbits treated by the hydrogel and BMSCs were repaired with hyaline-like tissue without obvious inflammation response. HE, safranin O, and immunohistochemical staining showed that the hyaline like cartilage was formed in cartilage defects, and the collagen content in the new generated cartilage was similar to the normal cartilage. The neocartilage was thinner than the surrounding normal cartilage, but it exhibited integration with adjacent healthy tissue. The abundant well-defined chondrocytes were aligned in several apparent chondrocyte clusters in the new generated cartilage.ConclusionsThe thermo-sensitive injectable CS/Col/PLA/GP composite hydrogel has better ability to promote survive, proliferation and chondrogenic differentiation of seeded BMSCs as compared against CS/Col/GP and CS/GP hydrogels. Combined with BMSCs to repair cartilage defects of rabbit knee joints, they can effectively reduce the cartilage defect area, and the new generated cartilage is comparable to normal cartilage structure. In addition, abundant availability and simple fabrication process also make CS/Col/PLA/GP composite hydrogel a suitable candidate scaffold in cartilage tissue engineering.

show abstract

An injectable continuous stratified structurally and functionally biomimetic construct for enhancing osteochondral regeneration

Cited by 124 publications

References 40 publications

miR‐23a‐3p‐abundant small extracellular vesicles released from Gelma/nanoclay hydrogel for cartilage regeneration

miR‐23a‐3p‐abundant small extracellular vesicles released from Gelma/nanoclay hydrogel for cartilage regeneration

A Physiology-Inspired Multifactorial Toolbox in Soft-to-Hard Musculoskeletal Interface Tissue Engineering

Efficacy of a Thermally Triggered Injectable Hydrogel CS/Col /PLA/GP and BMSCs for Cartilage Tissue Engineering

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