Dynamic hyaluronic acid hydrogel with covalent linked gelatin as an anti-oxidative bioink for cartilage tissue engineering

2021 ◽  
Author(s):  
Wen Shi ◽  
Fang Fang ◽  
Yunfan Kong ◽  
Sydney E Greer ◽  
Mitchell A Kuss ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Hyaluronic Acid ◽  
Therapeutic Option ◽  
Phenylboronic Acid ◽  
Cartilage Tissue Engineering ◽  
Covalent Bond ◽  
Cartilage Tissue ◽  
Poly Vinyl Alcohol ◽  
Extracellular Matrix Components

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.

scholarly journals TISSUE ENGINEERING: FROM RESEARCH TO CLINICAL APPLICATION IN REGENERATIVE MEDICINE

1970 ◽  
pp. 159-192
Author(s):  
Enrico Tognana ◽  
Lanfranco Callegaro
Keyword(s):  
Tissue Engineering ◽  
Extracellular Matrix ◽  
Hyaluronic Acid ◽  
Regenerative Medicine ◽  
Therapeutic Option ◽  
Cartilage Tissue ◽  
Sequence Of Events ◽  
Benzyl Esters ◽  
Tissue Restoration

Tissue engineering strategies have recently emerged as the most advanced therapeutic option presently available in regenerative medicine. Tissue engineering encompasses the use of cells and their molecules in artificial constructs that compensate for lost or impaired body functions. It is based upon scaffoldguided tissue regeneration and involves the seeding of porous, biodegradable scaffolds with donor cells, which become differentiated and mimic naturally occurring tissues. These tissue-engineered constructs are then implanted into the patient to replace diseased or damaged tissues. Our approach to regenerative medicine is based on hyaluronan derivative polymers. HYAFF® is a class of hyaluronan derivative polymers obtained by coupling reaction. The strategy behind the creation of these polymers was to improve the stability of the polymer by esterifying the free carboxyl group of glucuronic acid, frequently repeated along the hyaluronic acid chain, with different types of alcohols. Once esterification of the polymer has been obtained, the material can easily be processed to produce membranes, fibres, sponges, microspheres and other devices, by extrusion, lyophilization or spray drying. A broad variety of polymers can be subsequently generated either by changing the type of ester group introduced or the extent of the esterification. The benzyl esters of hyaluronan, termed HYAFF®-11, are one of the most characterized HYAFF® polymers, from both the physicochemical and biological viewpoints, produced starting from hyaluronan of about 200 KDa. The ideal scaffold for tissue engineering should provide an immediate support to cells and have mechanical properties matching those of the tissue being repaired. Gradually then the material should be resorbed, as the cells begin secreting their own extracellular matrix, thus allowing for an optimal integration between newformed and existing tissue. Extensive biocompatibility studies have demonstrated the safety of HYAFF® scaffolds and their ability to be resorbed in the absence of an inflammatory response. Moreover, when implanted tend to promote the recapitulation of the events that facilitate tissue repair. HYAFF®-11 three-dimensional matrices support the in vitro growth of highly viable chondrocytes and fibroblasts. Similarly, micro-perforated membrane supports the growth and differentiation of keratinocytes. These cells, previously expanded on plastic and hence seeded into the HYAFF® scaffold, produce a characteristic extracellular matrix rich in proteoglycans expressing the typical markers of the tissues of their origin. Hyaluronan presents a variety of multi-functional activity being both a structural and informational molecule. Investigation of hyaluronan synthesis and degradation, the identification of new receptors and binding proteins and the elucidation of hyaluronan-dependent signaling pathways keep providing novel insights into the true biological functions of this intriguing polymer. The possibility to elaborate this natural polymer in different physical forms, as HYAFF® biopolymers family is allowing to do, has given the opportunity to translate tissue engineering strategies in clinical practice providing a biomaterial that induces and modulates the sequence of events that lead to damage tissue restoration. The following chapter will report how tissue engineering approach and hyaluronic acid technology could improve the biological function of cell transplantation in the treatment of tissue defects, in particular for skin and cartilage tissue restoration.

Influence of Chondrocyte Zone on Co-Cultures With Mesenchymal Stem Cells in HA Hydrogels for Cartilage Tissue Engineering

2012 ◽  
Author(s):  
Minwook Kim ◽  
Jason A. Burdick ◽  
Robert L. Mauck
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Hyaluronic Acid ◽  
Articular Chondrocytes ◽  
Cartilage Tissue Engineering ◽  
3D Culture ◽  
Cartilage Tissue ◽  
Cell Type

Mesenchymal stem cells (MSCs) are an attractive cell type for cartilage tissue engineering in that they can undergo chondrogenesis in a variety of 3D contexts [1]. Focused efforts in MSC-based cartilage tissue engineering have recently culminated in the formation of biologic materials possessing biochemical and functional mechanical properties that match that of the native tissue [2]. These approaches generally involve the continuous or intermittent application of pro-chondrogenic growth factors during in vitro culture. For example, in one recent study, we showed robust construct maturation in MSC-seeded hyaluronic acid (HA) hydrogels transiently exposed to high levels of TGF-β3 [3]. Despite the promise of this approach, MSCs are a multipotent cell type and retain a predilection towards hypertrophic phenotypic conversion (i.e., bone formation) when removed from a pro-chondrogenic environment (e.g., in vivo implantation). Indeed, even in a chondrogenic environment, many MSC-based cultures express pre-hypertrophic markers, including type X collagen, MMP13, and alkaline phosphatase [4]. To address this issue, recent studies have investigated co-culture of human articular chondrocytes and MSCs in both pellet and hydrogel environments. Chondrocytes appear to enhance the initial efficiency of MSC chondrogenic conversion, as well as limit hypertrophic changes in some instances (potentially via secretion of PTHrP and/or other factors) [5–7]. While these findings are intriguing, articular cartilage has a unique depth-dependent morphology including zonal differences in chondrocyte identity. Ng et al. showed that zonal chondrocytes seeded in a bi-layered agarose hydrogel construct can recreate depth-dependent cellular and mechanical heterogeneity, suggesting that these identities are retained with transfer to 3D culture systems [8]. Further, Cheng et al. showed that differences in matrix accumulation and hypertrophy in zonal chondrocytes was controlled by bone morphogenic protein [9]. To determine whether differences in zonal chondrocyte identity influences MSC fate decisions, we evaluated functional properties and phenotypic stability in photocrosslinked hyaluronic acid (HA) hydrogels using distinct, zonal chondrocyte cell fractions co-cultured with bone marrow derived MSCs.

Alginate Microbeads as Cell Support for Cartilage Tissue Engineering: Bioreactor Studies

2007 ◽  
Vol 555 ◽  
pp. 417-422 ◽  
Author(s):  
B. Obradović ◽  
A. Osmokrović ◽  
B. Bugarski ◽  
D. Bugarski ◽  
G. Vunjak-Novaković
Keyword(s):  
Tissue Engineering ◽  
Mass Transport ◽  
Immobilized Cells ◽  
Cartilage Tissue Engineering ◽  
Packed Bed ◽  
Alginate Beads ◽  
Cartilage Tissue ◽  
Extracellular Matrix Components ◽  
Bioreactor System

Alginate was shown to be a suitable support for entrapment and cultivation of chondrocytes and bone marrow stromal cells, which under appropriate in vitro conditions synthesized cartilaginous components. The main limitation in these cultures may be low rates of mass transport through the alginate matrix governed by diffusion. In this study, we have designed and utilized a bioreactor system based on a packed bed of alginate beads with immobilized chondrogenic cells. Continuous medium perfusion provided convective mass transport through the packed bed, while small diameters of beads (2.5 mm and down to 500 μm) ensured short diffusion distances to the immobilized cells. During up to 5 weeks of cultivation, the cells synthesized extracellular matrix components merging beads together and indicating potentials of this system for precise regulation of the cellular microenvironment in cartilage tissue engineering.

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

Biomaterials ◽  
2011 ◽  
Vol 32 (25) ◽  
pp. 5773-5781 ◽  
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

scholarly journals Digital Light Processing Bioprinted Human Chondrocyte-Laden Poly (γ-Glutamic Acid)/Hyaluronic Acid Bio-Ink towards Cartilage Tissue Engineering

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 714
Author(s):  
Alvin Kai-Xing Lee ◽  
Yen-Hong Lin ◽  
Chun-Hao Tsai ◽  
Wan-Ting Chang ◽  
Tsung-Li Lin ◽  
...  
Keyword(s):  
United States ◽  
Tissue Engineering ◽  
Hyaluronic Acid ◽  
Glutamic Acid ◽  
Cellular Proliferation ◽  
Cartilage Tissue Engineering ◽  
Cartilage Regeneration ◽  
The United States ◽  
Cartilage Injury ◽  
Cartilage Tissue

Cartilage injury is the main cause of disability in the United States, and it has been projected that cartilage injury caused by osteoarthritis will affect 30% of the entire United States population by the year 2030. In this study, we modified hyaluronic acid (HA) with γ-poly(glutamic) acid (γ-PGA), both of which are common biomaterials used in cartilage engineering, in an attempt to evaluate them for their potential in promoting cartilage regeneration. As seen from the results, γ-PGA-GMA and HA, with glycidyl methacrylate (GMA) as the photo-crosslinker, could be successfully fabricated while retaining the structural characteristics of γ-PGA and HA. In addition, the storage moduli and loss moduli of the hydrogels were consistent throughout the curing durations. However, it was noted that the modification enhanced the mechanical properties, the swelling equilibrium rate, and cellular proliferation, and significantly improved secretion of cartilage regeneration-related proteins such as glycosaminoglycan (GAG) and type II collagen (Col II). The cartilage tissue proof with Alcian blue further demonstrated that the modification of γ-PGA with HA exhibited suitability for cartilage tissue regeneration and displayed potential for future cartilage tissue engineering applications. This study built on the previous works involving HA and further showed that there are unlimited ways to modify various biomaterials in order to further bring cartilage tissue engineering to the next level.

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

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
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.

TRENDS AND CHALLENGES OF CARTILAGE TISSUE ENGINEERING

2009 ◽  
Vol 21 (03) ◽  
pp. 149-155 ◽  
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.

scholarly journals Correction: An injectable hyaluronic acid/PEG hydrogel for cartilage tissue engineering formed by integrating enzymatic crosslinking and Diels–Alder “click chemistry”

2018 ◽  
Vol 9 (28) ◽  
pp. 3959-3960 ◽  
Author(s):  
Feng Yu ◽  
Xiaodong Cao ◽  
Yuli Li ◽  
Lei Zeng ◽  
Bo Yuan ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Hyaluronic Acid ◽  
Click Chemistry ◽  
Cartilage Tissue Engineering ◽  
Diels Alder ◽  
Cartilage Tissue

Correction for ‘An injectable hyaluronic acid/PEG hydrogel for cartilage tissue engineering formed by integrating enzymatic crosslinking and Diels–Alder “click chemistry”’ by Feng Yu et al., Polym. Chem., 2014, 5, 1082–1090.

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