A novel biomaterial for articular cartilage repair generated by self-assembly: a histopathological analysis for cartilage tissue engineering using a self-assembled biomaterial in rabbit knee joints

Articular cartilage repair remains a great clinical challenge. Tissue engineering approaches based on decellularized extracellular matrix (dECM) scaffolds show promise for facilitating articular cartilage repair. Traditional regenerative approaches currently used in clinical practice, such as microfracture, mosaicplasty, and autologous chondrocyte implantation, can improve cartilage repair and show therapeutic effect to some degree; however, the long-term curative effect is suboptimal. As dECM prepared by proper decellularization procedures is a biodegradable material, which provides space for regeneration tissue growth, possesses low immunogenicity, and retains most of its bioactive molecules that maintain tissue homeostasis and facilitate tissue repair, dECM scaffolds may provide a biomimetic microenvironment promoting cell attachment, proliferation, and chondrogenic differentiation. Currently, cell-derived dECM scaffolds have become a research hotspot in the field of cartilage tissue engineering, as ECM derived from cells cultured in vitro has many advantages compared with native cartilage ECM. This review describes cell types used to secrete ECM, methods of inducing cells to secrete cartilage-like ECM and decellularization methods to prepare cell-derived dECM. The potential mechanism of dECM scaffolds on cartilage repair, methods for improving the mechanical strength of cell-derived dECM scaffolds, and future perspectives on cell-derived dECM scaffolds are also discussed in this review.

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

10.21203/rs.3.rs-96928/v1 ◽

2020 ◽

Author(s):

Mingjing Li ◽

Fan Li

Keyword(s):

Tissue Engineering ◽

Mrna Expression ◽

Cartilage Tissue Engineering ◽

Knee Joints ◽

Cartilage Tissue ◽

Cartilage Defects ◽

Normal Cartilage ◽

Rabbit Knee ◽

Safranin O ◽

Thermally Triggered

Abstract 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.

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Biomarker Identification Under Growth Factor Priming for Cartilage Tissue Engineering

ASME 2012 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2012-80374 ◽

2012 ◽

Author(s):

Elena Alegre-Aguarón ◽

Sonal R. Sampat ◽

Perry J. Hampilos ◽

J. Chloë Bulinski ◽

James L. Cook ◽

...

Keyword(s):

Tissue Engineering ◽

Articular Cartilage ◽

Growth Factor ◽

Cartilage Repair ◽

Cartilage Tissue Engineering ◽

Cartilage Tissue ◽

Physical Factors ◽

Functional Tissue ◽

Cell Sources ◽

The Impact

Adult articular cartilage has a poor healing capacity, which has lead to intense research toward development of cell-based therapies for cartilage repair. The destruction of articular cartilage results in osteoarthritis (OA), which affects about 27 million Americans. In order to create functional tissue, it is essential to mimic the native environment by optimizing expansion protocols. Cell passaging and priming with chemical or physical factors are often necessary steps in cell-based strategies for regenerative medicine [1]. The ability to identify biomarkers that can act as predictors of cells with a high capacity to form functional engineered cartilage will permit optimization of protocols for cartilage tissue engineering using different cell sources. Recent investigations have shown that chondrocytes and synovium-derived stem cells (SDSCs) are promising cell sources for cartilage repair [2,3]. The analysis of gene expression and comparative proteomics, which defines the differences in expression of proteins among different biological states, provides a potentially powerful tool in this effort [4]. The aim of this study was to investigate the impact of growth factor priming in 2D canine chondrocytes and SDSCs cultures by identifying differentially regulated biomarkers, which can correlate to functional tissue elaboration in 3D.

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Experimental Model for Cartilage Tissue Engineering to Regenerate the Zonal Organization of Articular Cartilage

Osteoarthritis and Cartilage ◽

10.1016/s1063-4584(03)00120-1 ◽

2003 ◽

Vol 11 (9) ◽

pp. 653-664 ◽

Cited By ~ 183

Author(s):

T.-K Kim ◽

B Sharma ◽

C.G Williams ◽

M.A Ruffner ◽

A Malik ◽

...

Keyword(s):

Tissue Engineering ◽

Articular Cartilage ◽

Experimental Model ◽

Cartilage Tissue Engineering ◽

Cartilage Tissue ◽

Zonal Organization

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Bone and Articular Cartilage Tissue Engineering: The Biological Components

Biodegradable Systems in Tissue Engineering and Regenerative Medicine ◽

10.1201/9780203491232-33 ◽

2004 ◽

pp. 477-498

Keyword(s):

Tissue Engineering ◽

Articular Cartilage ◽

Cartilage Tissue Engineering ◽

Cartilage Tissue

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Hydrogels for the Application of Articular Cartilage Tissue Engineering: A Review of Hydrogels

Advances in Materials Science and Engineering ◽

10.1155/2018/4368910 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 9

Author(s):

Er-Yuan Chuang ◽

Chih-Wei Chiang ◽

Pei-Chun Wong ◽

Chih-Hwa Chen

Keyword(s):

Tissue Engineering ◽

Articular Cartilage ◽

Cartilage Damage ◽

Medical Science ◽

Cartilage Tissue Engineering ◽

Polymeric Materials ◽

Tissue Growth ◽

Cartilage Tissue ◽

Cellular Interaction ◽

Polymeric Hydrogels

The treatment of articular cartilage damage is a major task in the medical science of orthopedics. Hydrogels possess the ability to form multifunctional cartilage grafts since they possess polymeric swellability upon immersion in an aqueous phase. Polymeric hydrogels are capable of physiological swelling and greasing, and they possess the mechanical behavior required for use as articular cartilage substitutes. The chondrogenic phenotype of these materials may be enhanced by embedding living cells. Artificial hydrogels fabricated from biologically derived and synthesized polymeric materials are also used as tissue-engineering scaffolds; with their controlled degradation profiles, the release of stimulatory growth factors can be achieved. In order to make use of these hydrogels, cartilage implants were formulated in the laboratory to demonstrate the bionic mechanical behaviors of physiological cartilage. This paper discusses developments concerning the use of polymeric hydrogels for substituting injured cartilage tissue and assisting tissue growth. These gels are designed with consideration of their polymeric classification, mechanical strength, manner of biodegradation, limitations of the payload, cellular interaction, amount of cells in the 3D hydrogel, sustained release for the model drug, and the different approaches for incorporation into adjacent organs. This article also summarizes the different advantages, disadvantages, and the future prospects of hydrogels.

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