Injectable Thermosensitive Chitosan/Pullulan-Based Hydrogels with Improved Mechanical Properties and Swelling Capacity

Thermosensitive chitosan/β-glycerophosphate (CS/BGP) systems have been developed as injectable hydrogels. However, the hydrogels exhibited poor mechanical properties due to their physically crosslinked networks. In this work, CS/BGP hydrogels were reinforced by covalent crosslinking using genipin (GE) and concomitantly semi-interpenetrating networks using pullulan (PL). Based on response surface methodology, the optimized formulation was composed of CS (1.05%, w/v), PL (1%, w/v), BGP (6%, w/v), and GE (70.79 mcg/mL). The optimized hydrogels exhibited Young’s modulus of 92.65 ± 4.13 kPa and a percentage of equilibrium swelling ratio of 3259.09% ± 58.90%. Scanning electron micrographs revealed a highly porous structure with nanofibrous networks in the CS/PL/BGP/GE hydrogels. The chemical interactions between the compositions were investigated by Fourier-transform infrared spectroscopy. Rheological measurements illustrated that the optimized hydrogels displayed sol–gel transition within one minute at 37 °C, a lower critical solution temperature of about 31 °C, and viscoelastic behavior with high storage modulus. Furthermore, the optimized hydrogels demonstrated higher resistance to in vitro enzymatic degradation, compared to the hydrogels without GE. Our findings could suggest that the thermosensitive CS/PL/BGP/GE hydrogels with enhanced mechanical properties and swelling capacity demonstrate the potential for use as scaffolds and carriers for cartilage tissue engineering and drug delivery applications.

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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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A Novel Biodegradable and Thermosensitive Poly(Ester-Amide) Hydrogel for Cartilage Tissue Engineering

BioMed Research International ◽

10.1155/2018/2710892 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 2

Author(s):

Tsai-Sheng Fu ◽

Yu-Hong Wei ◽

Po-Yuan Cheng ◽

I-Ming Chu ◽

Wei-Chuan Chen

Keyword(s):

Tissue Engineering ◽

Diblock Copolymer ◽

Diblock Copolymers ◽

Sol Gel ◽

Cartilage Tissue Engineering ◽

Cell Encapsulation ◽

Cartilage Tissue ◽

Attractive Alternative ◽

Thermosensitive Hydrogels

Thermosensitive hydrogels are attractive alternative scaffolding materials for minimally invasive surgery through a simple injection and in situ gelling. In this study, a novel poly(ester-amide) polymer, methoxy poly(ethylene glycol)-poly(pyrrolidone-co-lactide) (mPDLA, P3L7) diblock copolymer, was synthesized and characterized for cartilage tissue engineering. A series of amphiphilic diblock copolymers was synthesized by ring-opening polymerization of mPEG 550, D,L-lactide, and 2-pyrrolidone. By dynamic light scattering analysis and tube-flipped-upside-down method, viscoelastic properties of the mPDLA diblock copolymer solution exhibited sol-gel transition behavior as a function of temperature. An in vitro degradation assay showed that degradation acidity was effectively reduced by introducing the 2-pyrrolidone monomer into the polyester hydrogel. Besides, mPDLA exhibited great biocompatibility in vitro for cell encapsulation due to a high swelling ratio. Moreover, cell viability and biochemical analysis proved that the mPDLA hydrogel presented a great chondrogenic response. Taken together, these results demonstrate that mPDLA hydrogels are promising injectable scaffolds potentially applicable to cartilage tissue engineering.

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A Collagen-Mimetic Organic-Inorganic Hydrogel for Cartilage Engineering

Gels ◽

10.3390/gels7020073 ◽

2021 ◽

Vol 7 (2) ◽

pp. 73

Author(s):

Laurine Valot ◽

Marie Maumus ◽

Luc Brunel ◽

Jean Martinez ◽

Muriel Amblard ◽

...

Keyword(s):

Mechanical Properties ◽

Sol Gel ◽

Cartilage Tissue Engineering ◽

Collagen Gel ◽

Cartilage Regeneration ◽

Cartilage Tissue ◽

Focal Lesions ◽

Hybrid Hydrogel ◽

Cartilage Engineering ◽

Functional Peptides

Promising strategies for cartilage regeneration rely on the encapsulation of mesenchymal stromal cells (MSCs) in a hydrogel followed by an injection into the injured joint. Preclinical and clinical data using MSCs embedded in a collagen gel have demonstrated improvements in patients with focal lesions and osteoarthritis. However, an improvement is often observed in the short or medium term due to the loss of the chondrocyte capacity to produce the correct extracellular matrix and to respond to mechanical stimulation. Developing novel biomimetic materials with better chondroconductive and mechanical properties is still a challenge for cartilage engineering. Herein, we have designed a biomimetic chemical hydrogel based on silylated collagen-mimetic synthetic peptides having the ability to encapsulate MSCs using a biorthogonal sol-gel cross-linking reaction. By tuning the hydrogel composition using both mono- and bi-functional peptides, we succeeded in improving its mechanical properties, yielding a more elastic scaffold and achieving the survival of embedded MSCs for 21 days as well as the up-regulation of chondrocyte markers. This biomimetic long-standing hybrid hydrogel is of interest as a synthetic and modular scaffold for cartilage tissue engineering.

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Development and Evaluation of Gellan Gum/Silk Fibroin/Chondroitin Sulfate Ternary Injectable Hydrogel for Cartilage Tissue Engineering

Biomolecules ◽

10.3390/biom11081184 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1184

Author(s):

Seongwon Lee ◽

Joohee Choi ◽

Jina Youn ◽

Younghun Lee ◽

Wooyoup Kim ◽

...

Keyword(s):

Mechanical Properties ◽

Tissue Engineering ◽

Chondroitin Sulfate ◽

Silk Fibroin ◽

Articular Chondrocytes ◽

Cartilage Tissue Engineering ◽

Cell Encapsulation ◽

Gellan Gum ◽

Cartilage Tissue

Hydrogel is in the spotlight as a useful biomaterial in the field of drug delivery and tissue engineering due to its similar biological properties to a native extracellular matrix (ECM). Herein, we proposed a ternary hydrogel of gellan gum (GG), silk fibroin (SF), and chondroitin sulfate (CS) as a biomaterial for cartilage tissue engineering. The hydrogels were fabricated with a facile combination of the physical and chemical crosslinking method. The purpose of this study was to find the proper content of SF and GG for the ternary matrix and confirm the applicability of the hydrogel in vitro and in vivo. The chemical and mechanical properties were measured to confirm the suitability of the hydrogel for cartilage tissue engineering. The biocompatibility of the hydrogels was investigated by analyzing the cell morphology, adhesion, proliferation, migration, and growth of articular chondrocytes-laden hydrogels. The results showed that the higher proportion of GG enhanced the mechanical properties of the hydrogel but the groups with over 0.75% of GG exhibited gelling temperatures over 40 °C, which was a harsh condition for cell encapsulation. The 0.3% GG/3.7% SF/CS and 0.5% GG/3.5% SF/CS hydrogels were chosen for the in vitro study. The cells that were encapsulated in the hydrogels did not show any abnormalities and exhibited low cytotoxicity. The biochemical properties and gene expression of the encapsulated cells exhibited positive cell growth and expression of cartilage-specific ECM and genes in the 0.5% GG/3.5% SF/CS hydrogel. Overall, the study of the GG/SF/CS ternary hydrogel with an appropriate content showed that the combination of GG, SF, and CS can synergistically promote articular cartilage defect repair and has considerable potential for application as a biomaterial in cartilage tissue engineering.

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Preparation and Characterization of Nanofibrous Polymer Scaffolds for Cartilage Tissue Engineering

Journal of Nanomaterials ◽

10.1155/2015/564087 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 13

Author(s):

Jarosław Markowski ◽

Anna Magiera ◽

Marta Lesiak ◽

Aleksander L. Sieron ◽

Jan Pilch ◽

...

Keyword(s):

Mechanical Properties ◽

Carbon Nanotubes ◽

Tissue Engineering ◽

Cartilage Tissue Engineering ◽

Physical And Mechanical Properties ◽

Biological Assessment ◽

Cartilage Tissue ◽

Poly Lactic Acid ◽

Fibrous Membranes

Polymer substrates obtained from poly(lactic acid) (PLA) nanofibres modified with carbon nanotubes (CNTs) and gelatin (GEL) for cartilage tissue engineering are studied. The work presents the results of physical, mechanical, and biological assessment. The hybrid structure of PLA and gelatine nanofibres, carbon nanotubes- (CNTs-) modified PLA nanofibres, and pure PLA-based nanofibres was manufactured in the form of fibrous membranes. The fibrous samples with different microstructures were obtained by electrospinning method. Microstructure, physical and mechanical properties of samples made from pure PLA nanofibres, CNTs-, and gelatin-modified PLA-nanofibres were studied. The scaffolds were also testedin vitroin cell culture of human chondrocytes collected from patients. To assess the influence of the nanofibrous scaffolds upon chondrocytes, tests for cytotoxicity and genotoxicity were performed. The work reveals that the nanofibrous structures studied were neither genotoxic nor cytotoxic, and their microstructure, physical and mechanical properties create promising scaffolds for potential use in cartilage repairing.

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Potential of 3-D tissue constructs engineered from bovine chondrocytes/silk fibroin-chitosan for in vitro cartilage tissue engineering

Biomaterials ◽

10.1016/j.biomaterials.2011.04.061 ◽

2011 ◽

Vol 32 (25) ◽

pp. 5773-5781 ◽

Cited By ~ 134

Author(s):

Nandana Bhardwaj ◽

Quynhhoa T. Nguyen ◽

Albert C. Chen ◽

David L. Kaplan ◽

Robert L. Sah ◽

...

Keyword(s):

Tissue Engineering ◽

Silk Fibroin ◽

Cartilage Tissue Engineering ◽

Cartilage Tissue ◽

Tissue Constructs

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Calcium/Cobalt Alginate Beads as Functional Scaffolds for Cartilage Tissue Engineering

Stem Cells International ◽

10.1155/2016/2030478 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 22

Author(s):

Stefano Focaroli ◽

Gabriella Teti ◽

Viviana Salvatore ◽

Isabella Orienti ◽

Mirella Falconi

Keyword(s):

Tissue Engineering ◽

Bone Morphogenetic Proteins ◽

Transforming Growth Factor ◽

Cartilage Tissue Engineering ◽

Biomechanical Properties ◽

Alginate Beads ◽

Cartilage Tissue ◽

Self Healing ◽

Tissue Replacement

Articular cartilage is a highly organized tissue with complex biomechanical properties. However, injuries to the cartilage usually lead to numerous health concerns and often culminate in disabling symptoms, due to the poor intrinsic capacity of this tissue for self-healing. Although various approaches are proposed for the regeneration of cartilage, its repair still represents an enormous challenge for orthopedic surgeons. The field of tissue engineering currently offers some of the most promising strategies for cartilage restoration, in which assorted biomaterials and cell-based therapies are combined to develop new therapeutic regimens for tissue replacement. The current study describes thein vitrobehavior of human adipose-derived mesenchymal stem cells (hADSCs) encapsulated within calcium/cobalt (Ca/Co) alginate beads. These novel chondrogenesis-promoting scaffolds take advantage of the synergy between the alginate matrix and Co+2ions, without employing costly growth factors (e.g., transforming growth factor betas (TGF-βs) or bone morphogenetic proteins (BMPs)) to direct hADSC differentiation into cartilage-producing chondrocytes.

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Cartilage Tissue Engineering Using Mesenchymal Stem Cells and 3D Chitosan Scaffolds – In vitro and in vivo Assays

Biomaterials Science and Engineering ◽

10.5772/25085 ◽

2011 ◽

Author(s):

Natalia Martins ◽

Alessandra Arcoverde ◽

Juliana Lott ◽

Viviane Silva ◽

Dawidson Gomes ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cartilage Tissue Engineering ◽

Cartilage Tissue ◽

In Vivo Assays ◽

Chitosan Scaffolds

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TRENDS AND CHALLENGES OF CARTILAGE TISSUE ENGINEERING

Biomedical Engineering Applications Basis and Communications ◽

10.4015/s1016237209001209 ◽

2009 ◽

Vol 21 (03) ◽

pp. 149-155 ◽

Cited By ~ 2

Author(s):

Hsu-Wei Fang

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Growth Factors ◽

Bone Cells ◽

Cartilage Tissue Engineering ◽

Bioactive Molecules ◽

In Vivo Studies ◽

Cartilage Tissue

Cartilage injuries may be caused by trauma, biomechanical imbalance, or degenerative changes of joint. Unfortunately, cartilage has limited capability to spontaneous repair once damaged and may lead to progressive damage and degeneration. Cartilage tissue-engineering techniques have emerged as the potential clinical strategies. An ideal tissue-engineering approach to cartilage repair should offer good integration into both the host cartilage and the subchondral bone. Cells, scaffolds, and growth factors make up the tissue engineering triad. One of the major challenges for cartilage tissue engineering is cell source and cell numbers. Due to the limitations of proliferation for mature chondrocytes, current studies have alternated to use stem cells as a potential source. In the recent years, a lot of novel biomaterials has been continuously developed and investigated in various in vitro and in vivo studies for cartilage tissue engineering. Moreover, stimulatory factors such as bioactive molecules have been explored to induce or enhance cartilage formation. Growth factors and other additives could be added into culture media in vitro, transferred into cells, or incorporated into scaffolds for in vivo delivery to promote cellular differentiation and tissue regeneration.Based on the current development of cartilage tissue engineering, there exist challenges to overcome. How to manipulate the interactions between cells, scaffold, and signals to achieve the moderation of implanted composite differentiate into moderate stem cells to differentiate into hyaline cartilage to perform the optimum physiological and biomechanical functions without negative side effects remains the target to pursue.

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