Multicomponent Hydrogel Research Articles

Development of reinforced chitosan/pectin scaffold by using the cellulose nanocrystals as nanofillers: An injectable hydrogel for tissue engineering

Injectable hydrogels based on chitosan (CS), cellulose nanocrystals (CNCs) and pectin were designed with the well internal structure that are significant for tissue engineering. Pectin and CS-based hydrogels that mimic the extracellular matrix (ECM) are widely used to maintain the balance between biofunctional and physical properties. While, these hydrogels display low mechanical strength limits their uses in cartilage repair. So, CNCs were employed as nanofillers to reinforce the hydrogels based on the natural polysaccharides. In this regard, the aim of this study was to improve the mechanical property of CS/pectin injectable hydrogels by introducing CNCs into the CS/pectin hydrogels. By varying their weight ratios, physicochemical properties of CS/pectin hydrogels with or without CNCs were characterized. The results indicated that with increasing the CNCs content, more compact network structure, lower equilibrium swelling ratios and better the resistance to degradation of composite hydrogels were observed. Furthermore, the incorporation of CNCs in CS/pectin hydrogels increased the proliferation of chondrocytes, demonstrating cell supportive properties of CNCs. This result was due to the higher potential interaction of cells with sulphate groups of CNC. These findings suggested that the novel multicomponent hydrogel can be a useful scaffold for cartilage tissue regeneration.

Growth‐Factor Free Multicomponent Nanocomposite Hydrogels That Stimulate Bone Formation

AbstractSynthetic osteo‐promoting materials that are able to stimulate and accelerate bone formation without the addition of exogenous cells or growth factors represent a major opportunity for an aging world population. A co‐assembling system that integrates hyaluronic acid tyramine (HA‐Tyr), bioactive peptide amphiphiles (GHK‐Cu2+), and Laponite (Lap) to engineer hydrogels with physical, mechanical, and biomolecular signals that can be tuned to enhance bone regeneration is reported. The central design element of the multicomponent hydrogels is the integration of self‐assembly and enzyme‐mediated oxidative coupling to optimize structure and mechanical properties in combination with the incorporation of an osteo‐ and angio‐promoting segments to facilitate signaling. Spectroscopic techniques are used to confirm the interplay of orthogonal covalent and supramolecular interactions in multicomponent hydrogel formation. Furthermore, physico‐mechanical characterizations reveal that the multicomponent hydrogels exhibit improved compressive strength, stress relaxation profile, low swelling ratio, and retarded enzymatic degradation compared to the single component hydrogels. Applicability is validated in vitro using human mesenchymal stem cells and human umbilical vein endothelial cells, and in vivo using a rabbit maxillary sinus floor reconstruction model. Animals treated with the HA‐Tyr‐HA‐Tyr‐GHK‐Cu2+ hydrogels exhibit significantly enhanced bone formation relative to controls including the commercially available Bio‐Oss.

Optimization of collagen-elastin-like polypeptide-bioglass scaffold composition for osteogenic differentiation of adipose-derived stem cells

We have developed a multicomponent hydrogel scaffold that can mimic the bone extracellular matrix by incorporating collagen, elastin-like polypeptide (ELP), and Bioglass. We examined the effects of Bioglass addition to collagen-ELP scaffolds on mechanical properties, physical characteristics, and in vitro osteogenic differentiation, by varying the Bioglass amount and particle size. Response surface methodology with a central composite design predicted 5 mg (6.6 mg/mL) Bioglass with a particle size of 142 ± 5 µm as the optimal amount and particle size to be mixed with 6 mg/mL collagen and 18 mg/mL ELP to obtain a combination of maximized compressive properties. Swelling ratio and FTIR spectroscopy indicated lower hydrophilicity and the presence of hydrophobic and secondary interactions between collagen, ELP, and Bioglass. Scanning electron microscopy showed a nanofibrous morphology of intermingled collagen-ELP-Bioglass network. In vitro osteogenic characterization using human adipose-derived stem cells revealed increased cell attachment and proliferation with increased ALP activity, osteocalcin content, and mineralized deposit formation during a three-week culture. Numerous mineralized deposits composed of calcium and phosphorous were shown by energy dispersive spectroscopy. Overall, our results show that the collagen-ELP-Bioglass multicomponent composites have enhanced mechanical properties with adequate physical features and cell culture properties for bone tissue engineering.

Accelerated and scarless wound repair by a multicomponent hydrogel through simultaneous activation of multiple pathways

Scarless healing of injury remains a clinical challenge because of its complicated and overlapping phases of inflammation, clearing, and regeneration. Curcumin has been already established as a potential wound healing agent for normal and diabetic-impaired wounds. Herein, the question has been addressed whether a well-known antioxidant cerium oxide nanoparticle (CNP) can potentiate the activity of curcumin to promote a cellular program for scarless healing. In this study, we have developed a biocompatible poly (acrylamide) hydrogel (PAGE)-based dressing material comprising of CNP and curcumin (ACC) and tested its wound healing activity in an animal model of acute wound. Characterization of the CNP- and curcumin-entrapped hydrogel dressing (ACC) demonstrated high loading efficiency and sustained release of curcumin. In a full-thickness acute wound healing model of rat, a single application of ACC dressing demonstrated higher wound healing efficacy (78%) and negligible scarring compared to dressings containing only curcumin or CNP in 7days. Enhanced cell proliferation, higher collagen content, advanced wound maturity, re-epithelialization, and granulation tissue formation were observed using the combination of curcumin and CNP (ACC). Study of cellular mechanisms identified MCP-1 and TGF-β as the key drivers of differential and accelerated healing observed in the ACC group. These, coupled with the upregulation of growth-related signaling pathways (HER2/ErbB2, TGF-β-Smad2/3, MAPK/ERK, AKT, and VEGF), promoted almost scarless healing in animals treated with ACC. The optimized combination of curcumin and CNP used in our study shows distinct advantage and can be a better agent for complete wound healing.

Post-assembly Fabrication of a Functional Multicomponent Supramolecular Hydrogel Based on a Self-Sorting Double Network.

Living cells exhibit sophisticated functions because they contain numerous endogenous stimuli-responsive molecular systems that independently and cooperatively act in response to an external circumstance. On the other hand, artificial soft materials containing multiple stimuli-responsive molecular systems are still rare. Herein, we demonstrate a unique multicomponent hydrogel composed of a self-sorting double network prepared through a post-assembly fabrication (PAF) protocol. The PAF protocol allowed the construction of a well-ordered hydrogel with a dual-biomolecule response to two important biomolecules (adenosine triphosphate (ATP) and sarcosine). Such a hydrogel could not be prepared through a one-step mixing protocol. The resultant multicomponent hydrogel responded to ATP and sarcosine through gel-sol transition behavior programmed in an AND logic gate fashion. Finally, we applied the multicomponent hydrogel to the controlled release of an antibody.

Effect of Mucoadhesive Polymeric Formulation on Corneal Permeation of Fluoroquinolones.

The aim of the study was to develop a novel formulation of levofloxacin and besifloxacin to achieve improved mucoadhesion and permeability of besifloxacin and levofloxacin through cornea for the effective treatment of ocular infections. A multicomponent hydrogel formulation containing chitosan-polyvinyl alcohol (PVA)-poly(N-vinylpyrrolidone) (PVP) was designed. Lysophosphatidylcholine was used to enhance corneal penetration of the drugs. The hydrogel preparations were characterized for various parameters, including clarity, pH, viscosity, in vitro release kinetics, mucoadhesion, ex vivo human corneal permeation, and antimicrobial efficacy. The formulations were compared with standard drug solution and marketed eye drops (Besix® and Levotop®). Compared to commercial ophthalmic preparations and free drug solutions, hydrogel formulation of both besifloxacin and levofloxacin was found to have 3.5- and 8-fold higher (P < 0.001) mucoadhesion and superior cumulative corneal permeation. The formulations showed superior in vitro anti-infective properties. Incubation of besifloxacin and levofloxacin formulations with Staphylococcus aureus-infected cornea model for 0.5 h showed greater potency of the hydrogel formulations compared to the marketed eye drops and standard solutions. The results of the study show the multicomponent hydrogel formulations of besifloxacin and levofloxacin to have superior corneal permeation with the potential for being used as topical ophthalmic preparations.

Engineered stem cell mimics to enhance stroke recovery

Currently, no medical therapies exist to augment stroke recovery. Stem cells are an intriguing treatment option being evaluated, but cell-based therapies have several challenges including developing a stable cell product with long term reproducibility. Since much of the improvement observed from cellular therapeutics is believed to result from trophic factors the stem cells release over time, biomaterials are well-positioned to deliver these important molecules in a similar fashion. Here we show that essential trophic factors secreted from stem cells can be effectively released from a multi-component hydrogel system into the post-stroke environment. Using our polymeric system to deliver VEGF-A and MMP-9, we improved recovery after stroke to an equivalent degree as observed with traditional stem cell treatment in a rodent model. While VEGF-A and MMP-9 have many unique mechanisms of action, connective tissue growth factor (CTGF) interacts with both VEGF-A and MMP-9. With our hydrogel system as well as with stem cell delivery, the CTGF pathway is shown to be downregulated with improved stroke recovery.

On-Demand Cascade Release of Hydrophobic Chemotherapeutics from a Multicomponent Hydrogel System.

A multicomponent hydrogel drug-delivery platform with covalent incorporation of core-cross-linked star (CCS) polymers has been fabricated through dual cross-linking reactions. The presence of amphiphilic CCS polymers enhances the mechanical stability of the network and allows for immobilization of hydrophobic chemotherapeutics (e.g., doxorubicin: DOX) within a hydrophilic matrix. Thanks to thiol-responsive disulfide segments, the hybrid network is selectively degradable upon exposure to the glutathione-rich tumor environment, leading to an on-demand cascade release of payloads in a prolonged manner. After network degradation, the integrity of the therapeutic cargos is still well-protected by the CCS polymeric carriers. A cellular study demonstrated efficient internalization of released drug-containing CCS polymers by HeLa cells, intracellular delivery of encapsulated drugs following pH-mediated erosion of the CCS containers, and excellent cytocompatibility of this hydrogel system.

Dynamic Bonds between Boronic Acid and Alginate: Hydrogels with Stretchable, Self-Healing, Stimuli-Responsive, Remoldable, and Adhesive Properties.

For the increasing demand of soft materials with wide ranges of applications, hydrogels have been developed exhibiting variety of functions (e.g., stretchable, self-healing, stimuli-responsive, and etc.). So far, add-in components such as inorganic nanoparticles, carbon materials, clays, and many others to main polymers have been used to achieve various unique functions of hydrogels. The multicomponent hydrogel systems often exhibit batch-dependent inconsistent results and problems in multicomponent mixings, require labors during preparations, and accompany unpredictable cross-talk between the added components. Here, we developed 'single polymeric component', alginate-boronic acid (alginate-BA) hydrogel to overcome the aforementioned problems. It exhibits unprecedented multifunctionalities simultaneously, such as high stretchability, self-healing, shear-thinning, pH- and glucose-sensitivities, adhesive properties, and reshaping properties. Multifunctionalities of alginate-BA hydrogel is resulted from the reversible inter- and intramolecular interactions by dynamic equilibrium of boronic acid-diol complexation and dissociation, which was proved by single molecule level Atomic Force Microscopy (AFM) pulling experiments. We also found that the alginate-BA gel showed enhanced in vivo retentions along gastrointestinal (GI) tract. Our findings suggest that rational polymer designs can result in minimizing the number of a participating component for multifunctional hydrogels, instead of increasing complexity by adding various additional components.

Large-area alginate/PEO-PPO-PEO hydrogels with thermoreversible rheology at physiological temperatures

Alginate hydrogels have shown great promise for applications in wound dressings, drug delivery, and tissue engineering. This report details the fabrication and rheological properties of a multicomponent hydrogel consisting of alginate and poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymers, and the achievement of thick, castable gels with tunable, thermoreversible behavior at physiological temperatures. PEO-PPO-PEO triblock copolymers can form temperature-sensitive hydrogels that exist as liquids at low temperatures and soft solids at high temperatures. In this work, we have employed PEO-PPO-PEO triblock copolymers to impart thermoresponsive properties to alginate hydrogels in the form of a multicomponent hydrogel. These systems can transition between a weak gel and a stiff gel, with a corresponding increase in the viscoelastic moduli of approximately two orders of magnitude as temperature is increased. The temperatures corresponding to the upper and lower boundaries of the stiff gel region, as well as the storage modulus at physiological temperatures (e.g., 36–40 °C), can be controlled through the PEO-PPO-PEO concentration. Optically clear gels that are homogeneous on the microscale can be fabricated in a scalable manner to create flat, large-area thick films, making these systems favorable for applications in wound healing, soft tissue repair, and biomedical device coatings.

Reducing Astrocytic Scarring after Traumatic Brain Injury with a Multifaceted Anti-Inflammatory Hydrogel System.

Traumatic brain injury results in devastating long-term functional damage due to the growth inhibition of the inflammatory response, and in particular, the complex response of astrocytes. Sustained, nonsteroidal anti-inflammatory approaches that can attenuate this response are of interest to improve therapeutic outcomes, particularly when combined with a tissue engineering construct that recapitulates the physiological microenvironment to facilitate functional repair. Here, we present a multifaceted, therapeutic extracellular-matrix mimic consisting of a coassembled scaffold with a laminin-inspired self-assembling peptide hydrogel, Fmoc-DIKVAV, and the anti-inflammatory macromolecule, fucoidan. At 7 days post-injury, our novel multicomponent hydrogel system presenting biologically relevant nanofibers and the anti-inflammatory fucoidan attenuated the primary glial scar to half that of a stab (control) injury. Further, the presentation of fucoidan increased the organization of astrocytes within the glial scar, while also significantly changing the morphology of astrocytes distal from the administered hydrogel and further into the parenchyma. This demonstrates that the anti-inflammatory fucoidan, present on the surface of the Fmoc-DIKVAV nanofibers, causes a change in astrocyte phenotype post-injury attenuating "reactive" astrocytosis. For the first time, we present a multicomponent tissue engineering construct to promote a growth-permissive environment in vivo and, thus, increase the potential for repair and regeneration after traumatic brain injury.

Controlled release of salmon calcitonin from multicomponent hydrogel

Controlled release of salmon calcitonin from multicomponent hydrogel

Bacteriostatic Characteristics of Bone Substituting Constructors Obtained from Composite Materials Based on Natural Polymers, Calcium Phosphates and Vancomycin

Introduction.The local delivery of therapeutic antibiotic concentrations to the zone of surgical intervention in bone pathology enables either to prevent or significantly decrease the rate of osteomyelitis development. It that study the efficacy of vancomycin inclusion and release from three dimensional constructors based on sodium alginate, gelatin and octacalcium phosphate and vancomycin intended for bone defect substitution was studied.Materials and methods. Prototyping of 3D constructors was performed by extrusion 3D printing. Various concentrations of vancomycin were added as an additional component at the stage of preparation of hydrogel (“ink”) for printing. Physical testing of the constructors included electron microscopic evaluation of their microstructure and porosity as well as the study of mechanical strength for compression and stretching. Functional activity of printed constructors with respect to the test strain S. aureus ATCC 6538-P was assessed by a disc-diffusion method in vitro and on the model of infected excision skin wound in rats -in vivo.Results. Analysis of the kinetic curves showed that the principal release of the drug in the model liquid took place within the first day. The total volume of the bound and released vancomycin made up approximately 20% of the calculated initial amount for all three concentrations. Formation of the marked growth inhibition zone of S. aureus strain in presence of vancomycin rich constructors was demonstrated in vitro. Insertion of constructors into the zone of infected skin defect resulted in a decrease of inflammatory processes severity and rate as well as accelerated the terms of complete wound healing.Conclusion. Study results showed the principle potentiality of bone substituting implants 3D-printing using multicomponent hydrogel compositions without change of separate components characteristics.

Bacteriostatic Characteristics of Bone Substituting Constructors Obtained from Composite Materials Based on Natural Polymers, Calcium Phosphates and Vancomycin

Introduction. The local delivery of therapeutic antibiotic concentrations to the zone of surgical intervention in bone pathology enables either to prevent or significantly decrease the rate of osteomyelitis development. It that study the efficacy of vancomycin inclusion and release from three dimensional constructors based on sodium alginate, gelatin and octacalcium phosphate and vancomycin intended for bone defect substitution was studied. Materials and methods . Prototyping of 3D constructors was performed by extrusion 3D printing. Various concentrations of vancomycin were added as an additional component at the stage of preparation of hydrogel (“ink”) for printing. Physical testing of the constructors included electron microscopic evaluation of their microstructure and porosity as well as the study of mechanical strength for compression and stretching. Functional activity of printed constructors with respect to the test strain S. aureus ATCC 6538-P was assessed by a disc-diffusion method in vitro and on the model of infected excision skin wound in rats - in vivo. Results . Analysis of the kinetic curves showed that the principal release of the drug in the model liquid took place within the first day. The total volume of the bound and released vancomycin made up approximately 20% of the calculated initial amount for all three concentrations. Formation of the marked growth inhibition zone of S. aureus strain in presence of vancomycin rich constructors was demonstrated in vitro. Insertion of constructors into the zone of infected skin defect resulted in a decrease of inflammatory processes severity and rate as well as accelerated the terms of complete wound healing. Conclusion. Study results showed the principle potentiality of bone substituting implants 3D-printing using multicomponent hydrogel compositions without change of separate components characteristics.

Two-component thermosensitive hydrogels: Phase separation affecting rheological behavior

Extracellular matrices are mainly composed of a mixture of different biopolymers and therefore the use of two or more building blocks for the development of tissue-mimicking hydrogels is nowadays an attractive strategy in tissue-engineering. Multi-component hydrogel systems may undergo phase separation, which in turn can lead to new, unexpected material properties. The aim of this study was to understand the role of phase separation on the mechanical properties and 3D printability of hydrogels composed of triblock copolymers of polyethylene glycol (PEG) and methacrylated poly(N-(2-hydroxypropyl) methacrylamide-mono/dilactate) (pHPMAlac) blended with methacrylated hyaluronic acid (HAMA). To this end, hydrogels composed of different concentrations of PEG/pHPMAlac and HAMA, were analyzed for phase behavior and rheological properties. Subsequently, phase separation and rheological behavior as function of the two polymer concentrations were mathematically processed to generate a predictive model. Results showed that PEG/pHPMAlac/HAMA hydrogels were characterized by hydrophilic, HAMA-richer internal domains dispersed in a more hydrophobic continuous phase, composed of PEG/pHPMAlac, and that the volume fraction of the dispersed phase increased by increasing HAMA concentration. Storage modulus, yield stress and viscosity increased with increasing HAMA concentration for low/medium HAMA contents (≤0.75% w/w), while a further increase of HAMA resulted in a decrease of the mentioned properties. On the other hand, by increasing the concentration of PEG/pHPMAlac these rheological properties were enhanced. The generated models showed a good fitting with experimental data, and were used to identify an exemplary 3D printability window for PEG/pHPMAlac/HAMA hydrogels, which was verified by rheological characterization and preparation of 3D printed scaffolds. In conclusion, a clear relationship between phase separation and rheological behavior in these two-component hydrogels can be described by complex functions of the two polymer concentrations. The predictive model generated in this study can be used as a valid tool for the identification of hydrogel compositions with desired, selected characteristics.

Self-crosslinking and injectable hyaluronic acid/RGD-functionalized pectin hydrogel for cartilage tissue engineering

In the present study, we developed a biomimetic injectable hydrogel system based on hyaluronic acid-adipic dihydrazide and the oligopeptide G4RGDS-grafted oxidized pectin, in which their hydrazide and aldehyde-derivatives enable covalent hydrazone crosslinking of polysaccharides. The hydrazone crosslinking strategy is simple, while circumventing toxicity, making this injectable system feasible, minimally invasive and easily translatable for regenerative purposes. By varying their weight ratios, the physicochemical properties of the mechanically stable hydrogel system were easily adjustable. Additionally, the preliminary studies demonstrated that chondrocyte behavior was dependent on HA/pectin composition and the presence of integrin binding moieties. Specifically, the incorporation of a certain amount of G4RGDS oligopeptide into HA/pectin-based hydrogels could serve as a biologically active microenvironment that supported chondrocyte phenotype and facilitated chondrogenesis. Furthermore, the hydrogel system exhibited acceptable tissue compatibility by using a mouse subcutaneous implantation model. Overall, the novel injectable multicomponent hydrogel presented here is expected to be useful biomaterial scaffold for cartilage tissue regeneration.

Hierarchical Self-Assembly of Amino Acid Derivatives into Enzyme-Responsive Luminescent Gel

In this study, a novel three-component hydrogel has been designed and fabricated via hierarchical self-assembly by amino acid derivative (NPPD), riboflavin (RF) and α-cyclodextrin (α-CD). These molecules were aggregated to form some fibrous structures based on hydrogen bond and π–π stacking. The results show that the hydrogel has a specific response to α-amylase and the fluorescence disappears once hydrolyzed. Therefore, this multi-component hydrogel has potential application in the field of drug delivery.

Microengineered Multicomponent Hydrogel Fibers: Combining Polyelectrolyte Complexation and Microfluidics.

Fiber-based techniques hold great potential toward the development of structures that mimic the architecture of fibrous tissues, such as tendon. Microfluidics and polyelectrolyte complexation are among the most widely used techniques for the fabrication of fibrous structures. In this work, we combined both techniques to generate hydrogel fibers with a fibrillar-like structure. For this, either methacrylated hyaluronic acid (MA-HA) or chondroitin sulfate (MA-CS) were mixed with alginate (ALG), being all negatively charged polysaccharides, combined with chitosan (CHT), which is positively charged, and separately injected into a microfluidic device. Through a continuous injection into a coagulation bath and subsequent photo-cross-linking, we could obtain multicomponent hydrogel fibers, which exhibited smaller fibrils aligned in parallel, whenever CHT was present. The biological performance was assessed upon encapsulation and further culture of tendon cells. Overall, the reported process did not affect cell viability and cells were also able to maintain their main function of producing extracellular matrix up to 21 days in culture. In summary, we developed a novel class of photo-cross-linkable multicomponent hydrogel fibers than can act as bioactive modulators of cell behavior.

A multi-responsive multicomponent hydrogel with micro-phase separation structure: Synthesis and special drug release

In this article, the multicomponent hydrogel was prepared by the copolymerization of the hydrophobic silicon-containing monomer tris(trimethylsiloxy)-3-methacryloxypropyl-sliane (TRIS) with the hydrophilic monomers 2-hydroxyethyl methacrylate (HEMA) and N-vinyl pyrrolidone (NVP). The ethanol extraction experiments as well as the FTIR, DSC results showed that the copolymerization was effective. The silicone hydrogel that had hydrophilic and hydrophobic phases could be loaded with hydrophilic drug (FITC) and hydrophobic drug (Nile Red) simultaneously. The drug release properties of the hydrogel were studied by taking advantage of its innate stimuli-responsiveness to solvent and pH. The release behaviors of hydrophilic and hydrophobic drugs were found to be solvent dependent. And the release behavior of hydrophilic drug was also pH sensitive. With the characteristics above, the silicone hydrogels can be good candidates for specified materials and may have broad applications in responsiveness, drug release, contact lens, etc.

Chondro-inductive injectable hydrogels for stem cell-based intervertebral disc tissue engineering

Event Abstract Back to Event Chondro-inductive injectable hydrogels for stem cell-based intervertebral disc tissue engineering Taryn Naidoo1, Jessica Frith1, Donna J. Menzies1, Clementine Pradal1, Andrew Cameron1, Ernst Wolvetang1, Lisbeth Grondahl2, Darryl Whitehead3, Stan Gronthos4, Andrew Zannettino4, Peter Ghosh5 and Justin Cooper-White1, 6, 7 1 University of Queensland, Australian Institute for Bioengineering and Nanotechnology, Australia 2 University of Queensland, School of Chemistry and Molecular Biosciences, Australia 3 University of Queensland, School of Biomedical Sciences, Australia 4 University of Adelaide, Centre for Stem Cell Research, Robinson Institute, Australia 5 Monash University, Monash Institute of Medical Research, Australia 6 CSIRO, Biomedical Manufacturing, Australia 7 University of Queensland, School of Chemical Engineering, Australia Stem cell-based therapies require easily manufactured, injectable biomaterials tailored for delivery to different tissue sites and at the same time, having the ability to impart directive cues to such cells. We report here on a bio-synthetic multicomponent hydrogel system that provides significant flexibility in terms of the available mechanical property slate, biofunctionality and utility as injectable materials. This new gel platform is made from a hydroxyphenol (HP) functionalised, highly branched poly(ethylene glycol) (PEG), with or without HP functionalized hyaluronic acid (HA), via an enzyme mediated, oxidative crosslinking method. The versatility of this hydrogel system was exemplified through variations in the degree of HP substitution, polymer concentration, type and concentration of crosslinking reagents, which resulted in a range of mechanical properties (0.1 – 25 kPa) and gelation kinetics (5 seconds – 10 minutes) for these gels. Co-crosslinking of the PEG-HP/HA-HP conjugates with full length Fibronectin (without needing to a priori modify them) and/or a sulfated polysaccharide (SP) encouraged attachment and spreading of human mesenchymal stem cells (hMSCs). Under in vitro long term culture conditions, the presence of the HA and SP was shown to induce chondrogenic gene upregulation and protein and GAG matrix secretion, in the absence of inductive media, but to inhibit osteogenesis (even in the presence of osteogenic media), in human MSCs (Figure 1). Under small animal model in vivo assessment, in-situ gelation and tissue integration (with and without hMSCs) was confirmed (Figure 2), along with evidence of ectopic chondrogenesis after 21 days. Successful outcomes from both in vitro and small animal model in vivo assessments confirm that this novel hydrogel system shows significant promise for cartilage tissue engineering applications. It is currently under long term assessment in a large animal (ovine) model of IVD disease, results of which will be presented. Keywords: Cell Differentiation, Hydrogel, Tissue Engineering, stem cell Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: New Frontier Oral Topic: Regenerative medicine: biomaterials for control of tissue induction Citation: Naidoo T, Frith J, Menzies DJ, Pradal C, Cameron A, Wolvetang E, Grondahl L, Whitehead D, Gronthos S, Zannettino A, Ghosh P and Cooper-White J (2016). Chondro-inductive injectable hydrogels for stem cell-based intervertebral disc tissue engineering. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.02659 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Taryn Naidoo Jessica Frith Donna J Menzies Clementine Pradal Andrew Cameron Ernst Wolvetang Lisbeth Grondahl Darryl Whitehead Stan Gronthos Andrew Zannettino Peter Ghosh Justin Cooper-White Google Taryn Naidoo Jessica Frith Donna J Menzies Clementine Pradal Andrew Cameron Ernst Wolvetang Lisbeth Grondahl Darryl Whitehead Stan Gronthos Andrew Zannettino Peter Ghosh Justin Cooper-White Google Scholar Taryn Naidoo Jessica Frith Donna J Menzies Clementine Pradal Andrew Cameron Ernst Wolvetang Lisbeth Grondahl Darryl Whitehead Stan Gronthos Andrew Zannettino Peter Ghosh Justin Cooper-White PubMed Taryn Naidoo Jessica Frith Donna J Menzies Clementine Pradal Andrew Cameron Ernst Wolvetang Lisbeth Grondahl Darryl Whitehead Stan Gronthos Andrew Zannettino Peter Ghosh Justin Cooper-White Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.