Hydrogels For Tissue Engineering Applications Research Articles

Effect of Stereolithography 3D Printing on the Properties of PEGDMA Hydrogels

Stereolithography (SLA)-based 3D printing has proven to have several advantages over traditional fabrication techniques as it allows for the control of hydrogel synthesis at a very high resolution, making possible the creation of tissue-engineered devices with microarchitecture similar to the tissues they are replacing. Much of the previous work in hydrogels for tissue engineering applications have utilised the ultraviolet (UV) chamber bulk photopolymerisation method for preparing test specimens. Therefore, it is essential to directly compare SLA 3D printing to this more traditional approach to elucidate the differences in hydrogels prepared by each fabrication method. Polyethyleneglycol dimethacrylate (PEGDMA) is an ideally suited material for a comparative study of the impact that SLA fabrication has on performance, as the properties of traditional UV chamber-cured hydrogels have been extensively characterised. The present study was conducted to compare the material properties of PEGDMA hydrogels prepared using UV chamber photopolymerisation and SLA 3D printing. From the subsequent testing, SLA-fabricated hydrogels were shown to maintain similar thermal and chemical performance to UV chamber-cured hydrogels but had a higher compressive strength and tensile stiffness, as well as increased hydrophilicity. These differences are attributed to the increased exposure to UV light SLA samples received compared to traditionally UV chamber-cured samples.

Synthetic ECM: Bioactive Synthetic Hydrogels for 3D Tissue Engineering.

The specific microenvironment that cells reside in fundamentally impacts their broader function in tissues and organs. At its core, this microenvironment is composed of precise arrangements of cells that encourage homotypic and heterotypic cell-cell interactions, biochemical signaling through soluble factors like cytokines, hormones, and autocrine, endocrine, or paracrine secretions, and the local extracellular matrix (ECM) that provides physical support and mechanobiological stimuli, and further regulates biochemical signaling through cell-ECM interactions like adhesions and growth factor sequestering. Each cue provided in the microenvironment dictates cellular behavior and, thus, overall potential to perform tissue and organ specific function. It follows that in order to recapitulate physiological cell responses and develop constructs capable of replacing damaged tissue, we must engineer the cellular microenvironment very carefully. Many great strides have been made toward this goal using various three-dimensional (3D) tissue culture scaffolds and specific media conditions. Among the various 3D biomimetic scaffolds, synthetic hydrogels have emerged as a highly tunable and tissue-like biomaterial well-suited for implantable tissue-engineered constructs. Because many synthetic hydrogel materials are inherently bioinert, they minimize unintentional cell responses and thus are good candidates for long-term implantable grafts, patches, and organs. This review will provide an overview of commonly used biomaterials for forming synthetic hydrogels for tissue engineering applications and techniques for modifying them to with bioactive properties to elicit the desired cell responses.

Hydrogels from silk fibroin and multiarmed hydrolyzed elastin peptide

Ideal hydrogels for tissue engineering applications should mimic the properties of native extracellular matrices and optimize the cell behavior. Silk fibroin (SF) that possesses tunable mechanical strength and low cytotoxicity and elastin protein that stimulates cell viability are complementary for hybrid hydrogels. Here, hydrolyzed elastin peptide (HEP) and reconstituted SF (RSF) are combined to generate hybrid hydrogels. Physical cross-links are β-sheet conformation induced by heat in SF, and chemical cross-links are induced between HEP and RSF by glutaraldehyde (GA). The influence of the hybrid ratio on the molecular structure and mechanical properties is studied in detail. Results show that with only 0·1% GA, the non-gelling multiarmed HEP could accelerate the physical gelation process of SF to result in a homogeneous dual-cross-linked structure. The β-sheet conformation increases linearly with the SF content. The hybrid hydrogels possess compressive moduli of 4–70 kPa and shear storage moduli of 0·005 to ∼40 kPa, demonstrating tunable mechanical properties to cover a stiffness spectrum for various soft-tissue applications. Cell culture results suggest little cytotoxicity of such dual-cross-linked hybrid hydrogels. The hybrid hydrogels can be used as bioinks or biocoatings for tissue engineering.

Naturally Derived Photoinitiators for Dental and Biomaterials Applications

AbstractBiocompatibility of materials used in dental and biomaterials applications is very important and depends on the components of these materials. Photopolymerized materials for dental and biomaterials applications have been progressively used since the 1970s. One of the crucial components in these materials is the photoinitiator (PI) that initiates the polymerization reaction. Synthetic PIs are the most commonly used types, but owing to their drawbacks such as cytotoxicity, insolubility in water, and high cost, research on naturally derived (bio-sourced) PIs is growing, to find an alternative to these synthetic types, especially in the growing field of three-dimensional (3D) printing and bioprinting of biomaterials for tissue engineering applications. Naturally derived PIs are biocompatible, highly water-soluble, and abundant. Naturally derived PIs have been used to prepare experimental dentine bonding agents, dentine primers, photo-crosslinked hydrogels for tissue engineering applications, antibacterial coatings, guided tissue regeneration membranes, and 3D printed biomaterials. An electronic search was done using MEDLINE/PubMed and Scopus databases using the keywords naturally derived, bio-sourced, PIs, dental, biomaterials, 3D printing, and 3D bioprinting, to review potential naturally derived PIs for dental and biomaterials applications. There are a variety of naturally derived PIs with various colors and absorption spectra to choose from, according to the intended application. Most of naturally derived PIs can be used with modern conventional dental light curing units, making them applicable for experimental studies for potential dental and biomaterials applications. Due to their biocompatibility and availability it is expected that in the upcoming years, research on naturally derived PIs and their dental and biomaterials applications will increase especially in the growing field of 3D bioprinting in which cell viability is essential; thus this review was done.

Light Processable Starch Hydrogels.

Light processable hydrogels were successfully fabricated by utilizing maize starch as raw material. To render light processability, starch was gelatinized and methacrylated by simple reaction with methacrylic anhydride. The methacrylated starch was then evaluated for its photocuring reactivity and 3D printability by digital light processing (DLP). Hydrogels with good mechanical properties and biocompatibility were obtained by direct curing from aqueous solution containing lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) as photo-initiator. The properties of the hydrogels were tunable by simply changing the concentration of starch in water. Photo-rheology showed that the formulations with 10 or 15 wt% starch started curing immediately and reached G’ plateau after only 60 s, while it took 90 s for the 5 wt% formulation. The properties of the photocured hydrogels were further characterized by rheology, compressive tests, and swelling experiments. Increasing the starch content from 10 to 15 wt% increased the compressive stiffness from 13 to 20 kPa. This covers the stiffness of different body tissues giving promise for the use of the hydrogels in tissue engineering applications. Good cell viability with human fibroblast cells was confirmed for all three starch hydrogel formulations indicating no negative effects from the methacrylation or photo-crosslinking reaction. Finally, the light processability of methacrylated starch by digital light processing (DLP) 3D printing directly from aqueous solution was successfully demonstrated. Altogether the results are promising for future application of the hydrogels in tissue engineering and as cell carriers

3D printable and injectable lactoferrin-loaded carboxymethyl cellulose-glycol chitosan hydrogels for tissue engineering applications.

In this study, carboxymethyl cellulose (CMC)-glycol chitosan (GC) hydrogel, a potential three-dimensional (3D) printing biomaterial ink for tissue engineering applications was synthesized using simple, biocompatible in situ-gelling Schiff's base reaction and ionic interactions. Different grades of hydrogels (C70G30, C50G50 and C30G70) were synthesized at physiological conditions. The oxidation of CMC and imine bond formation in the hydrogel were confirmed spectroscopically. Scanning electron microscopic images revealed the crosslinked interconnected pores in the cross-sectioned hydrogels (dried). Swelling (equilibrium: 1 h), porosity (~75%), in vitro degradation (>30 days) and thermal gravimetric analyses of the dried gels were studied. Initially, cytotoxicity assay was evaluated using mouse osteoblastic cells (MC3T3). These experiments revealed that CMC-GC gels formed stable hydrogel networks and were biocompatible. Particularly, C50G50 gels showed high printability (continuous extrusion) and post-printing stability (without secondary crosslinking). Gel 3D printing was optimized by varying the air pressure, temperature, needle size and nozzle speed, to obtain stable lattice structures (2 to 16 layers). The printed (2 and 5 layers) hydrogels showed high stability in phosphate buffer saline (PBS) solution (1 h), under UV light (1 h) and after autoclaving. The strut dimensions and porosity of the printed gels before and after the stability tests were analyzed. The hydrogel stability may be attributed to both the imine bond and ionic interaction between the cationic and anionic polymer side chains. Lactoferrin (glycoprotein) incorporated C50G50 gels showed sustained release up to 21 days in PBS (pH 7.4) solution and demonstrated increased biocompatibility (>80%) during in vitro cytotoxicity assays (MC3T3 cells and bone marrow mesenchymal stem cells) and Live/Dead assay (MC3T3 cells). A higher number of live osteoblast cells on the C50G50 hydrogels with increasing lactoferrin concentration was observed. These results show that the CMC-GC gels are promising bio-ink candidates for 3D printing and loading proteins or drugs for tissue engineering applications.

Nanocomposite hydrogels for tissue engineering applications.

Tissue engineering is an important field of regenerative medicine, which combines scaffolds and cell transplantation to develop substitute tissues and/or promote tissue regeneration. Hydrogels, a three-dimensional network with high water content and biocompatibility, have been widely used as scaffolds to mimic the structure and properties of tissues. However, the low mechanical strength and limited functions of traditional hydrogels greatly limited their applications in tissue engineering. Recently, nanocomposite hydrogels, with its advantages of high mechanical property and some unique properties (such as electrical conductivity, antibacterial, antioxidation, magnetic responsiveness), have emerged as the most versatile and innovative technology, which provides a new opportunity as a unique tool for fabricating hydrogels with excellent properties. In this review, we summarize the recent advances in fabricating nanocomposite hydrogels and their applications in tissue engineering. In addition, the future and prospects of nanocomposite hydrogels for tissue engineering are also discussed.

Preparation of cellulose nanocrystal/oxidized dextran/gelatin (CNC/OD/GEL) hydrogels and fabrication of a CNC/OD/GEL scaffold by 3D printing

Early reports have demonstrated the feasibility of oxidized dextran/gelatin (OD/GEL) hydrogel for tissue engineering applications and the printability of OD/GEL hydrogel for 3D printing scaffolds, but adequate insight into fabricated OD/GEL scaffolds is lacking. In the present study, we prepared (cellulose nanocrystal) CNC/OD/GEL hydrogels and fabricated CNC/OD/GEL scaffolds by 3D printing. The properties of CNC/OD/GEL hydrogels were investigated by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy. The process of 3D printing of hydrogels was optimized, and the influence of the OD and CNC contents on the printability of CNC/OD/GEL hydrogels was investigated by studying the width of the printed filaments. The uniaxial compression test was performed to study the effects of the OD and CNC contents on the breaking strength and elastic modulus of CNC/OD/GEL scaffolds. In addition, the uniaxial compression test was also performed to determine the optimum mass ratio and crosslinking time of OD and GEL. The effects of the CNC content on scaffold shrinkage, scaffold swelling and scaffold porosity were further studied. The biocompatibility of a CNC0.4OD2G2 scaffold was also investigated by Cell Counting Kit-8 (CCK-8) and Hoechst 33342/PI double-staining assays. Collectively, the results confirmed the good potential of the CNC/OD/GEL hydrogels as 3D bioink for application in tissue repair.

Soft-Nanoparticle Functionalization of Natural Hydrogels for Tissue Engineering Applications.

Tissue engineering has emerged as an important research area that provides numerous research tools for the fabrication of biologically functional constructs that can be used in drug discovery, disease modeling, and the treatment of diseased or injured organs. From a materials point of view, scaffolds have become an important part of tissue engineering activities and are usually used to form an environment supporting cellular growth, differentiation, and maturation. Among various materials used as scaffolds, hydrogels based on natural polymers are considered one of the most suitable groups of materials for creating tissue engineering scaffolds. Natural hydrogels, however, do not always provide the physicochemical and biological characteristics and properties required for optimal cell growth. This review discusses the properties and tissue engineering applications of widely used natural hydrogels. In addition, methods of modulation of their physicochemical and biological properties using soft nanoparticles as fillers or reinforcing agents are presented.

Quantum Dots: Application of Ti3C2 MXene Quantum Dots for Immunomodulation and Regenerative Medicine (Adv. Healthcare Mater. 16/2019)

Ti3C2 MXene quantum dots (MQDs) are immunomodulatory and can be loaded into an injectable chitosan (CS)-based hydrogel for tissue engineering applications. In article number 1900569, Sanjiv Dhingra and co-workers show that injection of a CS-MQD hydrogel to an infarct site after coronary artery occlusion may reduce recruitment of immune cells and limit secondary injury to the heart.

Evaluation of the materials properties, stability and cell response of a range of PEGDMA hydrogels for tissue engineering applications

The main aim of this study was to examine the stability of a range of polyethyleneglycol dimethacrylate (PEGDMA) hydrogels over a 28-day period in simulated physiological solution. Upon optimisation of the ultraviolet (UV) curing conditions, the PEGDMA hydrogels were prepared using four different monomer concentrations (25, 50, 75 and 100 wt% PEGDMA) in water and cross-linked by photopolymerisation. Initial results revealed a correlation between monomer concentration and swelling behaviour, where a decrease in swelling was observed with increase in monomer content. On storage in physiological solutions at 37 °C, a decrease in the weight remaining of the hydrogels and the pH of the solutions was observed over a 28-day period. Using scanning electron microscopy, the surface topography of the hydrogels appeared to get smoother and in parallel changes in hydrophilicty were observed, with the biggest changes observed for the higher monomer concentrations where water contact angle values were seen to increase toward 90°. However, the mechanical properties remained relatively unaffected and there was no adverse effect on cell metabolic activity observed for cells grown in the presence of PEGDMA samples or using elution methods. Looking at the combination of mechanical chemical and thermal properties shown these results are an important finding for scaffolds intended for tissue engineering applications, where provision of mechanical support without the elicitation of an inflammatory response due to polymer degradation products is crucial for successful integration and neotissue formation during the first 28 days post implantation.

3D Bioprinted Nanocellulose-Based Hydrogels for Tissue Engineering Applications: A Brief Review.

Nanocellulosic materials, such as cellulose nanocrystals, cellulose nanofibers, and bacterial nanocellulose, that display high surface area, mechanical strength, biodegradability, and tunable surface chemistry have attracted great attention over the last decade for biomedical applications. Simultaneously, 3D printing is revolutionizing the field of biomedical engineering, which enables the fast and on-demand printing of customizable scaffolds, tissues, and organs. Nanocellulosic materials hold tremendous potential for 3D bioprinting due to their printability, their shear thinning behavior, their ability to live cell support and owing to their excellent biocompatibility. The amalgamation of nanocellulose-based feedstocks and 3D bioprinting is therefore of critical interest for the development of advanced functional 3D hydrogels. In this context, this review briefly discusses the most recent key developments and challenges in 3D bioprinting nanocellulose-based hydrogel constructs that have been successfully tested for mammalian cell viability and used in tissue engineering applications.

Photochemically crosslinked cell-laden methacrylated collagen hydrogels with high cell viability and functionality.

Irgacure 2959 (I2959) is widely used as a photoinitiator for photochemical crosslinking of hydrogels. However, the free radicals generated from I2959 have been reported to be highly cytotoxic. In this study, methacrylated collagen (CMA) hydrogels were photochemically crosslinked using two different photoinitiators (i.e., I2959 and VA086) and the effect of photoinitiator type, photoinitiator concentration (i.e., 0.02 and 0.1%) and crosslinking time (1 and 10 min) on gel morphology, compressive modulus, and stability were investigated. In addition, Saos-2 cells were encapsulated within the hydrogels and the effect of photochemical crosslinking conditions on cell viability, metabolic activity, and osteoblast functionality was assessed. Scanning electron microscopy imaging showed that photochemical crosslinking decreased the porosity of the hydrogels resulting in decrease in water retention ability compared to uncrosslinked hydrogels. On the other hand, photochemical crosslinking improved the stability of CMA hydrogels (p < 0.05). Uniaxial compression tests showed that increasing the photoinitiator concentration significantly improved the compressive modulus of CMA hydrogels (p < 0.05). Results from the live-dead assay showed that VA086 crosslinked hydrogels exhibited higher cell viability compared to I2959 (p < 0.05) crosslinked hydrogels indicating that VA086 is more cytocompatible compared to I2959. Furthermore, Alizarin Red S staining revealed a significantly more pronounced cell-mediated mineralization on VA086 crosslinked hydrogels (p < 0.05) indicating that Saos-2 cells retain their normal functionality in the presence of VA086. In summary, these results indicate that VA086 is a more biocompatible photoinitiator compared to I2959 for the generation of photochemically crosslinked CMA hydrogels for tissue engineering applications. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2019.

Incorporation of types I and III collagen in tunable hyaluronan hydrogels for vocal fold tissue engineering

Vocal fold scarring is the fibrotic manifestation of a variety of voice disorders, and is difficult to treat. Tissue engineering therapies provide a potential strategy to regenerate the native tissue microenvironment in order to restore vocal fold functionality. However, major challenges remain in capturing the complexity of the native tissue and sustaining regeneration. We hypothesized that hydrogels with tunable viscoelastic properties that present relevant biological cues to cells might be better suited as therapeutics. Herein, we characterized the response of human vocal fold fibroblasts to four different biomimetic hydrogels: thiolated hyaluronan (HA) crosslinked with poly(ethylene glycol) diacrylate (PEGDA), HA-PEGDA with type I collagen (HA-Col I), HA-PEGDA with type III collagen (HA-Col III) and HA-PEGDA with type I and III collagen (HA-Col I-Col III). Collagen incorporation allowed for interpenetrating fibrils of collagen within the non-fibrillar HA network, which increased the mechanical properties of the hydrogels. The addition of collagen fibrils also reduced hyaluronidase degradation of HA and hydrogel swelling ratio. Fibroblasts encapsulated in the HA-Col gels adopted a spindle shaped fibroblastic morphology by day 7 and exhibited extensive cytoskeletal networks by day 21, suggesting that the incorporation of collagen was essential for cell adhesion and spreading. Cells remained viable and synthesized new DNA throughout 21 days of culture. Gene expression levels significantly differed between the cells encapsulated in the different hydrogels. Relative fold changes in gene expression of MMP1, COL1A1, fibronectin and decorin suggest higher degrees of remodeling in HA-Col I-Col III gels in comparison to HA-Col I or HA-Col III hydrogels, suggesting that the former may better serve as a natural biomimetic hydrogel for tissue engineering applications. Statement of SignificanceVoice disorders affect about 1/3rd of the US population and significantly reduce quality of life. Patients with vocal fold fibrosis have few treatment options. Tissue engineering therapies provide a potential strategy to regenerate the native tissue microenvironment in order to restore vocal fold functionality. Various studies have used collagen or thiolated hyaluronan (HA) with gelatin as potential tissue engineering therapies. However, there is room for improvement in providing cells with more relevant biological cues that mimic the native tissue microenvironment and sustain regeneration. The present study introduces the use of type I collagen and type III collagen along with thiolated HA as a natural biomimetic hydrogel for vocal fold tissue engineering applications.

Second harmonic generation microscopy of collagen organization in tunable, environmentally responsive alginate hydrogels.

We fabricated photocrosslinked, environmentally responsive alginate hydrogels for tissue engineering applications. Methacrylated alginate (ALGMA) hydrogels were prepared across a variety and combination of ionic and covalent (chain growth, step growth, and mixed mode) crosslinking strategies to obtain a range of compressive moduli from 9.3 ± 0.2 kPa for the softest ionically crosslinked hydrogels to 22.6 ± 0.3 kPa for the dually crosslinked ionic mixed mode gels. The swelling behavior of the alginate hydrogels was significantly higher under basic pH conditions. Stiffer gels consistently swelled to a lesser degree compared to softer gels for all conditions. These hydrogels were stable - retaining >80% of their original mass for three weeks - when incubated in a basic solution of diluted sodium hydroxide, which mimicked accelerated degradation conditions. Encapsulated NIH/3T3 fibroblasts remained viable and proliferated significantly more in stiffer hydrogel substrates compared to softer gels. Additionally, the collagen secreted by encapsulated fibroblasts was quantifiably compared using second harmonic generation (SHG) imaging. Fibroblasts encapsulated in the softer hydrogels secreted significantly less collagen than the stiffer gels. The collagen in these softer gels was also more aligned than the stiffer gels. The ability to tune collagen organization using hydrogels has potential applications ranging from corneal wound healing where organized collagen is desired to epithelial wound scaffolds where a random organization is preferable.

Self-Healing Supramolecular Hydrogels for Tissue Engineering Applications.

Self-healing supramolecular hydrogels have emerged as a novel class of biomaterials that combine hydrogels with supramolecular chemistry to develop highly functional biomaterials with advantages including native tissue mimicry, biocompatibility, and injectability. These properties are endowed by the reversibly cross-linked polymer network of the hydrogel. These hydrogels have great potential for realizing yet to be clinically translated tissue engineering therapies. This review presents methods of self-healing supramolecular hydrogel formation and their uses in tissue engineering as well as future perspectives.

Incorporation of Conductive Materials into Hydrogels for Tissue Engineering Applications.

In the field of tissue engineering, conductive hydrogels have been the most effective biomaterials to mimic the biological and electrical properties of tissues in the human body. The main advantages of conductive hydrogels include not only their physical properties but also their adequate electrical properties, which provide electrical signals to cells efficiently. However, when introducing a conductive material into a non-conductive hydrogel, a conflicting relationship between the electrical and mechanical properties may develop. This review examines the strengths and weaknesses of the generation of conductive hydrogels using various conductive materials such as metal nanoparticles, carbons, and conductive polymers. The fabrication method of blending, coating, and in situ polymerization is also added. Furthermore, the applications of conductive hydrogel in cardiac tissue engineering, nerve tissue engineering, and bone tissue engineering and skin regeneration are discussed in detail.

Tough Photocrosslinked Silk Fibroin/Graphene Oxide Nanocomposite Hydrogels.

The development of protein-based hydrogels for tissue engineering applications is often limited by their mechanical properties. Herein, we present the facile fabrication of tough regenerated silk fibroin (RSF)/graphene oxide (GO) nanocomposite hydrogels by a photochemical cross-linking method. The RSF/GO composite hydrogels demonstrated soft and adhesive properties during initial stages of photocrosslinking (<2 min), which is not observed for the pristine RSF hydrogel, and rendered a tough and nonadhesive hydrogel upon complete cross-linking (10 min). The composite hydrogels exhibited superior tensile mechanical properties, increased β-sheet content, and decreased chain mobility compared to that of the pristine RSF hydrogels. The composite hydrogels demonstrated Young's modulus as high as ∼8 MPa, which is significantly higher than native cartilage (∼1.5 MPa), and tensile toughness as high as ∼2.4 MJ/m3, which is greater than that of electroactive polymer muscles and at par with RSF/GO composite membranes fabricated by layer-by-layer assembly. Small-angle scattering study reveals the hierarchical structure of photocrosslinked RSF hydrogels to comprise randomly distributed water-poor (hydrophobic) and water-rich (hydrophilic) regions at the nanoscale, whereas water pores and channels exhibiting fractal-like characteristics at the microscale. The size of hydrophobic domain (containing β-sheets) was observed to increase slightly with GO incorporation and/or alcohol post-treatment, whereas the size of the hydrophilic domain (intersheet distance containing random coils) was observed to increase significantly, which influences/affects water uptake capacity, cross-link density, and mechanical properties of hydrogels. The presented results have implications for both fundamental understanding of the structure-property relationship of RSF-based hydrogels and their technological applications.

Collagen/chitosan/hyaluronic acid - based injectable hydrogels for tissue engineering applications - design, physicochemical and biological characterization.

Studies on synthesis, physico-chemical and biological properties of novel biomimetic materials, potentially useful as injectable hydrogels are presented. These materials are in situ prepared chemically crosslinked collagen/chitosan/hyaluronic acid-based hydrogels exhibiting potential for tissue regeneration. Optimization of hydrogels involved testing the effect of various concentration of crosslinking agent (genipin) as well as different ratios of biopolymers used on their properties. The changes in the content of hyaluronic acid and in the genipin concentration used have been shown to be crucial. Employing the highest concentration of crosslinking agent studied (20 mM) the hydrogels of compact structure, characterized by good mechanical properties and prolonged degradation profile can be obtained. Changing the HA content in sol mixture the hydrogel of various wettability; more or less hydrophilic when compared to pure collagen/chitosan hydrogels can be fabricated. The in vitro cell culture study has shown that the surface of the prepared materials ensures suitable biocompatibility. These hydrogels can support the proliferation and adhesion of MG-63 cell line as it was demonstrated using Alamar Blue assay and SEM observations. It is believed that the collagen/chitosan/hyaluronic acid hydrogels crosslinked with genipin are particularly promising materials for bone regeneration procedures, especially attractive for regeneration of small bone losses. This is the first paper in the litearature presenting results of studies on that type of biopolymeric injectable hydrogels chemically crosslinked with genipin.

Click Chemistry and Material Selection for in Situ Fabrication of Hydrogels in Tissue Engineering Applications.

This Review gives a brief introduction to hydrogels formed through click chemistry for applications in tissue engineering. Specifically, we focus on three representative click chemistry mechanisms: Diels-Alder reactions, azide-alkyne cycloaddition, and thiol-ene chemistry. Apart from that, we also discuss photoinitiated chain growth polymerization, which also has fast kinetics. The chemical mechanisms of these reactions, along with their advantages and disadvantages, are presented. These gelation methods are compared and contrasted with other methods of forming hydrogels. Further, we offer an insight on the fabrication of click chemistry hydrogels from a material selection perspective. Commonly used materials from both synthetic and naturally derived polymer families were selected and discussed with their special features and drawbacks in fabricating hydrogels used in tissue engineering applications. At the end, the impact of cross-linking mechanisms and hydrogels properties on the host response is discussed. In conclusion, click reactions are modular and stereospecific. These reactions proceed rapidly with high selectivity, which means they have the potential to be formed in situ with minimal interference on biological processes. In order to achieve optimal hydrogels for tissue engineering applications, it is important to consider different design principles and material fabrication strategies to develop optimal hydrogels for regenerative medicine applications.