Electrospun chitosan/poly(vinyl alcohol) reinforced with CaCO3 nanoparticles with enhanced mechanical properties and biocompatibility for cartilage tissue engineering

Abstract Cartilage tissue engineering has arisen as a promising therapeutic option for degenerative joint diseases, such as osteoarthritis, in the hope of restoring the structure and physiological functions. Hydrogels are promising biomaterials for developing engineered constructs for cartilage regeneration. However, such cell-laden constructs could be exposed to elevated levels of reactive oxygen species (ROS) in the inflammatory microenvironment after being implanted into injured joints, which may affect their phenotype and normal functions and thereby hinder the regeneration efficacy. To attenuate ROS induced side effects, a multifunctional hydrogel with an innate anti-oxidative ability was produced in this study. The hydrogel was rapidly formed through a dynamic covalent bond between phenylboronic acid grafted hyaluronic acid (HA-PBA) and poly (vinyl alcohol) (PVA) and was further stabilized through a secondary crosslinking between the acrylate moiety on HA-PBA and the free thiol group from thiolated gelatin. The hydrogel is cyto-compatible and injectable and can be used as a bioink for 3D bioprinting. The viscoelastic properties of the hydrogels could be modulated through the hydrogel precursor concentration. The presence of dynamic covalent linkages contributed to its shear-thinning property and thus good printability of the hydrogel, resulting in the fabrication of a porous grid construct and a meniscus like scaffold at high structural fidelity. The bioprinted hydrogel promoted cell adhesion and chondrogenic differentiation of encapsulated rabbit adipose derived mesenchymal stem cells. Meanwhile, the hydrogel supported robust deposition of extracellular matrix components, including glycosaminoglycans and type II collagen, by embedded mouse chondrocytes in vitro. Most importantly, the hydrogel could protect encapsulated chondrocytes from ROS induced downregulation of cartilage-specific anabolic genes (ACAN and COL2) and upregulation of a catabolic gene (MMP13) after incubation with H2O2. Furthermore, intra-articular injection of the hydrogel in mice revealed adequate stability and good biocompatibility in vivo. These results demonstrate that this hydrogel can be used as a novel bioink for the generation of 3D bioprinted constructs with anti-ROS ability to potentially enhance cartilage tissue regeneration in a chronic inflammatory and elevated ROS microenvironment.

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Polyethylene glycol diacrylate scaffold filled with cell-laden methacrylamide gelatin/alginate hydrogels used for cartilage repair

Journal of Biomaterials Applications ◽

10.1177/08853282211044853 ◽

2021 ◽

pp. 088532822110448

Author(s):

Xiang Zhang ◽

Zhenhao Yan ◽

Guotao Guan ◽

Zijing Lu ◽

Shujie Yan ◽

...

Keyword(s):

Mechanical Properties ◽

Tissue Engineering ◽

Polyethylene Glycol ◽

Cartilage Tissue Engineering ◽

Cartilage Tissue ◽

High Concentration ◽

Polyethylene Glycol Diacrylate ◽

Low Concentration ◽

Glycol Diacrylate

Natural cartilage tissue has excellent mechanical properties and has certain cellular components. At this stage, it is a great challenge to produce cartilage scaffolds with excellent mechanical properties, biocompatibility, and biodegradability. Hydrogels are commonly used in tissue engineering because of their excellent biocompatibility; however, the mechanical properties of commonly used hydrogels are difficult to meet the requirements of making cartilage scaffolds. The mechanical properties of high concentration polyethylene glycol diacrylate (PEGDA) hydrogel are similar to those of natural cartilage, but its biocompatibility is poor. Low concentration hydrogel has better biocompatibility, but its mechanical properties are poor. In this study, two different hydrogels were combined to produce cartilage scaffolds with good mechanical properties and strong biocompatibility. First, the PEGDA grid scaffold was printed with light curing 3D printing technology, and then the low concentration GelMA/Alginate hydrogel with chondral cells was filled into the PEGDA grid scaffold. After a series of cell experiments, the filling hydrogel with the best biocompatibility was screened out, and finally the filled hydrogel with cells and excellent biocompatibility was obtained. Cartilage tissue engineering scaffolds with certain mechanical properties were found to have a tendency of cartilage formation in in vitro culture. Compared with the scaffold obtained by using a single hydrogel, this molding method can produce a tissue engineering scaffold with excellent mechanical properties on the premise of ensuring biocompatibility, which has a certain potential application value in the field of cartilage tissue engineering.

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Carboxymethyl Cellulose Entrapped in a Poly(vinyl) Alcohol Network: Plant-Based Scaffolds for Cartilage Tissue Engineering

Molecules ◽

10.3390/molecules26030578 ◽

2021 ◽

Vol 26 (3) ◽

pp. 578

Author(s):

Jirapat Namkaew ◽

Panitporn Laowpanitchakorn ◽

Nuttapong Sawaddee ◽

Sirinee Jirajessada ◽

Sittisak Honsawek ◽

...

Keyword(s):

Tissue Engineering ◽

Carboxymethyl Cellulose ◽

Cell Attachment ◽

Cartilage Tissue Engineering ◽

Crosslinking Density ◽

Cartilage Tissue ◽

Poly Vinyl Alcohol ◽

Porous Scaffolds ◽

Swelling Properties ◽

Engineered Cartilage

Cartilage has a limited inherent healing capacity after injury, due to a lack of direct blood supply and low cell density. Tissue engineering in conjunction with biomaterials holds promise for generating cartilage substitutes that withstand stress in joints. A major challenge of tissue substitution is creating a functional framework to support cartilage tissue formation. Polyvinyl alcohol (PVA) was crosslinked with glutaraldehyde (GA), by varying the mole ratios of GA/PVA in the presence of different amounts of plant-derived carboxymethyl cellulose (CMC). Porous scaffolds were created by the freeze-drying technique. The goal of this study was to investigate how CMC incorporation and crosslinking density might affect scaffold pore formation, swelling behaviors, mechanical properties, and potential use for engineered cartilage. The peak at 1599 cm−1 of the C=O group in ATR–FTIR indicates the incorporation of CMC into the scaffold. The glass transition temperature (Tg) and Young’s modulus were lower in the PVA/CMC scaffold, as compared to the PVA control scaffold. The addition of CMC modulates the pore architecture and increases the swelling ratio of scaffolds. The toxicity of the scaffolds and cell attachment were tested. The results suggest that PVA/CMC scaffolding material can be tailored in terms of its physical and swelling properties to potentially support cartilage formation.

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