scholarly journals A Rapid Crosslinkable Maleimide-Modified Hyaluronic Acid and Gelatin Hydrogel Delivery System for Regenerative Applications

Gels ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. 13
Author(s):  
Kyung Min Yoo ◽  
Sean V. Murphy ◽  
Aleksander Skardal

Hydrogels have played a significant role in many applications of regenerative medicine and tissue engineering due to their versatile properties in realizing design and functional requirements. However, as bioengineered solutions are translated towards clinical application, new hurdles and subsequent material requirements can arise. For example, in applications such as cell encapsulation, drug delivery, and biofabrication, in a clinical setting, hydrogels benefit from being comprised of natural extracellular matrix-based materials, but with defined, controllable, and modular properties. Advantages for these clinical applications include ultraviolet light-free and rapid polymerization crosslinking kinetics, and a cell-friendly crosslinking environment that supports cell encapsulation or in situ crosslinking in the presence of cells and tissue. Here we describe the synthesis and characterization of maleimide-modified hyaluronic acid (HA) and gelatin, which are crosslinked using a bifunctional thiolated polyethylene glycol (PEG) crosslinker. Synthesized products were evaluated by proton nuclear magnetic resonance (NMR), ultraviolet visibility spectrometry, size exclusion chromatography, and pH sensitivity, which confirmed successful HA and gelatin modification, molecular weights, and readiness for crosslinking. Gelation testing both by visual and NMR confirmed successful and rapid crosslinking, after which the hydrogels were characterized by rheology, swelling assays, protein release, and barrier function against dextran diffusion. Lastly, biocompatibility was assessed in the presence of human dermal fibroblasts and keratinocytes, showing continued proliferation with or without the hydrogel. These initial studies present a defined, and well-characterized extracellular matrix (ECM)-based hydrogel platform with versatile properties suitable for a variety of applications in regenerative medicine and tissue engineering.

Author(s):  
Enrico Tognana ◽  
Lanfranco Callegaro

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.


Author(s):  
Cong Wang ◽  
Hongye Hao ◽  
Jing Wang ◽  
Yunfan Xue ◽  
Jun-jie Huang ◽  
...  

As a component of extracellular matrix (ECM), hyaluronic acid (HA) has plenty of applications in biomedical field such as tissue engineering. Due to its non-adhesive nature, HA requires further functional...


Nanomaterials ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1587
Author(s):  
Caterina Cristallini ◽  
Emanuela Vitale ◽  
Claudia Giachino ◽  
Raffaella Rastaldo

To deliver on the promise of cardiac regeneration, an integration process between an emerging field, nanomedicine, and a more consolidated one, tissue engineering, has begun. Our work aims at summarizing some of the most relevant prevailing cases of nanotechnological approaches applied to tissue engineering with a specific interest in cardiac regenerative medicine, as well as delineating some of the most compelling forthcoming orientations. Specifically, this review starts with a brief statement on the relevant clinical need, and then debates how nanotechnology can be combined with tissue engineering in the scope of mimicking a complex tissue like the myocardium and its natural extracellular matrix (ECM). The interaction of relevant stem, precursor, and differentiated cardiac cells with nanoengineered scaffolds is thoroughly presented. Another correspondingly relevant area of experimental study enclosing both nanotechnology and cardiac regeneration, e.g., nanoparticle applications in cardiac tissue engineering, is also discussed.


2019 ◽  
Vol 20 (24) ◽  
pp. 6208 ◽  
Author(s):  
Jiyoung Hong ◽  
Miji Yeo ◽  
Gi Hoon Yang ◽  
GeunHyung Kim

Electrospinning has gained great interest in the field of regenerative medicine, due to its fabrication of a native extracellular matrix-mimicking environment. The micro/nanofibers generated through this process provide cell-friendly surroundings which promote cellular activities. Despite these benefits of electrospinning, a process was introduced to overcome the limitations of electrospinning. Cell-electrospinning is based on the basic process of electrospinning for producing viable cells encapsulated in the micro/nanofibers. In this review, the process of cell-electrospinning and the materials used in this process will be discussed. This review will also discuss the applications of cell-electrospun structures in tissue engineering. Finally, the advantages, limitations, and future perspectives will be discussed.


2014 ◽  
Vol 5 ◽  
pp. BTRI.S12331 ◽  
Author(s):  
John W. Cassidy

Modern medicine faces a growing crisis as demand for organ transplantations continues to far outstrip supply. By stimulating the body's own repair mechanisms, regenerative medicine aims to reduce demand for organs, while the closely related field of tissue engineering promises to deliver “of-the-self” organs grown from patients' own stem cells to improve supply. To deliver on these promises, we must have reliable means of generating complex tissues. Thus far, the majority of successful tissue engineering approaches have relied on macroporous scaffolds to provide cells with both mechanical support and differentiative cues. In order to engineer complex tissues, greater attention must be paid to nanoscale cues present in a cell's microenvironment. As the extracellular matrix is capable of driving complexity during development, it must be understood and reproduced in order to recapitulate complexity in engineered tissues. This review will summarize current progress in engineering complex tissue through the integration of nanocomposites and biomimetic scaffolds.


Author(s):  
Angela Seawright ◽  
Altug Ozcelikkale ◽  
J. Craig Dutton ◽  
Bumsoo Han

Cryopreservation can provide long-term storage of various biological tissues, which has significant impact on tissue engineering and regenerative medicine. For successful cryopreservation of tissues, tissue functionality must be maintained including physical properties such as mechanical, optical, and transport properties, as well as cellular viability. Such properties are associated with the extracellular matrix (ECM) microstructure. Thus, the preservation of the ECM microstructure may lead to successful cryopreservation [1,2]. Yet, there is still very little known about changes in the ECM microstructure during freezing/thawing.


2014 ◽  
Vol 10 (1) ◽  
pp. 214-223 ◽  
Author(s):  
Peter A. Levett ◽  
Ferry P.W. Melchels ◽  
Karsten Schrobback ◽  
Dietmar W. Hutmacher ◽  
Jos Malda ◽  
...  

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