Silanized Hydroxypropyl Methylcellulose Research Articles

Injectable Hydrogel Membrane for Guided Bone Regeneration.

In recent years, multicomponent hydrogels such as interpenetrating polymer networks (IPNs) have emerged as innovative biomaterials due to the synergistic combination of the properties of each network. We hypothesized that an innovative non-animal IPN hydrogel combining self-setting silanized hydroxypropyl methylcellulose (Si-HPMC) with photochemically cross-linkable dextran methacrylate (DexMA) could be a valid alternative to porcine collagen membranes in guided bone regeneration. Calvaria critical-size defects in rabbits were filled with synthetic biphasic calcium phosphate granules in conjunction with Si-HPMC; DexMA; or Si-HPMC/DexMA experimental membranes; and in a control group with a porcine collagen membrane. The synergistic effect obtained by interpenetration of the two polymer networks improved the physicochemical properties, and the gel point under visible light was reached instantaneously. Neutral red staining of murine L929 fibroblasts confirmed the cytocompatibility of the IPN. At 8 weeks, the photo-crosslinked membranes induced a similar degree of mineral deposition in the calvaria defects compared to the positive control, with 30.5 ± 5.2% for the IPN and 34.3 ± 8.2% for the collagen membrane. The barrier effect appeared to be similar in the IPN test group compared with the collagen membrane. In conclusion, this novel, easy-to-handle and apply, photochemically cross-linkable IPN hydrogel is an excellent non-animal alternative to porcine collagen membrane in guided bone regeneration procedures.

Embedding MSCs in Si-HPMC hydrogel decreased MSC-directed host immune response and increased the regenerative potential of macrophages.

Embedding mesenchymal stromal cells (MSCs) in biomaterial is a subject of increasing interest in the field of Regenerative Medicine. Speeding up the clinical use of MSCs is dependent on the use of non-syngeneic models in accordance with Good Manufacturing Practices (GMP) requirements and on costs. To this end, in this study, we analyzed the in vivo host immune response following local injection of silanized hydroxypropyl methylcellulose (Si-HPMC)-embedded human MSCs in a rat model developing colorectal damage induced by ionizing radiation. Plasma and lymphocytes from mesenteric lymph nodes were harvested in addition to colonic tissue. We set up tests, using flow cytometry and a live imaging system, to highlight the response to specific antibodies and measure the cytotoxicity of lymphocytes against injected MSCs. We demonstrated that Si-HPMC protects MSCs from specific antibodies production and from apoptosis by lymphocytes. We also observed that Si-HPMC does not modify innate immune response infiltrate in vivo, and that in vitro co-culture of Si-HPMC-embedded MSCs impacts macrophage inflammatory response depending on the microenvironment but, more importantly, increases the macrophage regenerative response through Wnt-family and VEGF gene expression. This study furthers our understanding of the mechanisms involved, with a view to improving the therapeutic benefits of biomaterial-assisted cell therapy by modulating the host immune response. The decrease in specific immune response against injected MSCs protected by Si-HPMC also opens up new possibilities for allogeneic clinical use.

Structural and biological investigation of chitosan/hyaluronic acid with silanized-hydroxypropyl methylcellulose as an injectable reinforced interpenetrating network hydrogel for cartilage tissue engineering

Cartilage damage continues to pose a threat to humans, but no treatment is currently available to fully restore cartilage function. In this study, a new class of composite hydrogels derived from water-soluble chitosan (CS)/hyaluronic acid (HA) and silanized-hydroxypropyl methylcellulose (Si-HPMC) (CS/HA/Si-HPMC) has been synthesized and tested as injectable hydrogels for cartilage tissue engineering when combined without the addition of a chemical crosslinking agent. Mechanical studies of CS/HA and CS/HA/Si-HPMC hydrogels showed that as Si-HPMC content increased, swelling rate and rheological properties were higher, compressive strength decreased and degradation was faster. Our results demonstrate that the CS and HA-based hydrogel scaffolds, especially the ones with 3.0% (w/v) Si-HPMC and 2.5/4.0% (w/v) CS/HA, have suitable physical performance and bioactive properties, thus provide a potential opportunity to be used for cartilage tissue engineering. In vitro studies of CS/HA and CS/HA/Si-HPMC hydrogels encapsulated in chondrocytes have shown that the proper amount of Si-HPMC increases the proliferation and deposition of the cartilage extracellular matrix. The regeneration rate of the CS/HA/Si-HPMC (3%) hydrogel reached about 79.5% at 21 days for long retention periods, indicating relatively good in vivo bone regeneration. These CS/HA/Si-HPMC hydrogels are promising candidates for tissue compatibility injectable scaffolds. The data provide proof of the principle that the resulting hydrogel has an excellent ability to repair joint cartilage using a tissue-engineered approach. RESEARCH HIGHLIGHTS An injectable hydrogel based on CS/HA/Si-HPMC composites was developed. The CS/HA/Si-HPMC hydrogel displays the tunable rheological with mechanical properties. The CS/HA/Si-HPMC hydrogel is highly porous with high swelling and degradation ratio. Increasing concentration of Si-HPMC promote an organized network in CS/HA/Si-HPMC hydrogels. Injectable CS/HA/Si-HPMC hydrogels have a high potential for cartilage tissue engineering.

Silanization of Chitosan and Hydrogel Preparation for Skeletal Tissue Engineering.

Tissue engineering is a multidisciplinary field that relies on the development of customized biomaterial to support cell growth, differentiation and matrix production. Toward that goal, we designed the grafting of silane groups onto the chitosan backbone (Si-chito) for the preparation of in situ setting hydrogels in association with silanized hydroxypropyl methylcellulose (Si-HPMC). Once functionalized, the chitosan was characterized, and the presence of silane groups and its ability to gel were demonstrated by rheology that strongly suggests the presence of silane groups. Throughout physicochemical investigations, the Si-HPMC hydrogels containing Si-chito were found to be stiffer with an injection force unmodified. The presence of chitosan within the hydrogel has demonstrated a higher adhesion of the hydrogel onto the surface of tissues. The results of cell viability assays indicated that there was no cytotoxicity of Si-chito hydrogels in 2D and 3D culture of human SW1353 cells and human adipose stromal cells, respectively. Moreover, Si-chito allows the transplantation of human nasal chondrocytes in the subcutis of nude mice while maintaining their viability and extracellular matrix secretory activity. To conclude, Si-chito mixed with Si-HPMC is an injectable, self-setting and cytocompatible hydrogel able to support the in vitro and in vivo viability and activity of hASC.

In situ photochemical crosslinking of hydrogel membrane for Guided Tissue Regeneration

ObjectivePeriodontitis is an inflammatory disease that destroys the tooth-supporting attachment apparatus. Guided tissue regeneration (GTR) is a technique based on a barrier membrane designed to prevent wound space colonization by gingival cells. This study examined a new formulation composed of two polymers that could be photochemically cross-linked in situ into an interpenetrated polymer network (IPN) forming a hydrogel membrane. MethodsWe synthetized and characterized silanized hydroxypropyl methylcellulose (Si-HPMC) for its cell barrier properties and methacrylated carboxymethyl chitosan (MA-CMCS) for its degradable backbone to use in IPN. Hydrogel membranes were cross-linked using riboflavin photoinitiator and a dentistry visible light lamp. The biomaterial’s physicochemical and mechanical properties were determined. Hydrogel membrane degradation was evaluated in lysozyme. Cytocompatibility was estimated by neutral red uptake. The cell barrier property was studied culturing human primary gingival fibroblasts or human gingival explants on membrane and analyzed with confocal microscopy and histological staining. ResultsThe IPN hydrogel membrane was obtained after 120s of irradiation. The IPN showed a synergistic increase in Young moduli compared with the single networks. The CMCS addition in IPN allows a progressive weight loss compared to each polymer network. Cytocompatibility was confirmed by neutral red assay. Human cell invasion was prevented by hydrogel membranes and histological sections revealed that the biomaterial exhibited a barrier effect in contact with soft gingival tissue. SignificanceWe demonstrated the ability of an innovative polymer formulation to form in situ, using a dentist’s lamp, an IPN hydrogel membrane, which could be an easy-to-use biomaterial for GTR therapy.

Water dynamics in silanized hydroxypropyl methylcellulose based hydrogels designed for tissue engineering

Silanized hydroxypropyl methylcellulose based hydrogels were developed for cartilage and intervertebral disc tissue engineering. Herein, study of dynamics of confined water showed two different populations, identified as hydration and bulk-like water. The diffusion coefficient showed that bulk-like water diffuses over distances ∼10 μm without being affected by the hydrogel matrix. Addition of silica nanofibers leads to improved mechanical properties and enhanced diffusion coefficient. Good diffusion within hydrogels is essential for the application.

Application of Millifluidics to Encapsulate and Support Viable Human Mesenchymal Stem Cells in a Polysaccharide Hydrogel

Human adipose-derived stromal cells (hASCs) are widely known for their immunomodulatory and anti-inflammatory properties. This study proposes a method to protect cells during and after their injection by encapsulation in a hydrogel using a droplet millifluidics technique. A biocompatible, self-hardening biomaterial composed of silanized-hydroxypropylmethylcellulose (Si-HPMC) hydrogel was used and dispersed in an oil continuous phase. Spherical particles with a mean diameter of 200 μm could be obtained in a reproducible manner. The viability of the encapsulated hASCs in the Si-HPMC particles was 70% after 14 days in vitro, confirming that the Si-HPMC particles supported the diffusion of nutrients, vitamins, and glucose essential for survival of the encapsulated hASCs. The combination of droplet millifluidics and biomaterials is therefore a very promising method for the development of new cellular microenvironments, with the potential for applications in biomedical engineering.

A Cellulose/Laponite Interpenetrated Polymer Network (IPN) Hydrogel: Controllable Double-Network Structure with High Modulus.

Laponite XLS™, which is a synthetic clay of nanometric dimensions containing a peptizing agent, has been associated with silanized hydroxypropylmethylcellulose (Si-HPMC) to form, after crosslinking, a novel composite hydrogel. Different protocols of sample preparation were used, leading to different morphologies. A key result was that the storage modulus of Si-HPMC/XLS composite hydrogel could be increased ten times when compared to that of pure Si-HPMC hydrogel using 2 wt % of Laponite. The viscoelastic properties of the composite formulations indicated that chemical and physical network structures co-existed in the Si-HPMC/XLS composite hydrogel. Images that were obtained from confocal laser scanning microscopy using labelled Laponite XLS in the composite hydrogels show two co-continuous areas: red light area and dark area. The tracking of fluorescent microspheres motions in the composite formulations revealed that the red-light area was a dense structure, whereas the dark area was rather loose without aggregated Laponite. This novel special double-network structure facilitates the composite hydrogel to be an adapted biomaterial for specific tissue engineering. Unfortunately, cytotoxicity’s assays suggested that XLS Laponites are cytotoxic at low concentration. This study validates that the hybrid interpenetrated network IPN hydrogel has a high modulus that has adapted for tissue engineering, but the cell’s internalization of Laponites has to be controlled.

Assessing glucose and oxygen diffusion in hydrogels for the rational design of 3D stem cell scaffolds in regenerative medicine.

Hydrogels are attractive biomaterials for replicating cellular microenvironments, but attention needs to be given to hydrogels diffusion properties. A large body of literature shows the promise of hydrogels as 3D culture models, cell expansion systems, cell delivery vehicles, and tissue constructs. Surprisingly, literature seems to have overlooked the important effects of nutrient diffusion on the viability of hydrogel-encapsulated cells. In this paper, we present the methods and results of an investigation into glucose and oxygen diffusion into a silated-hydroxypropylmethylcellulose (Si-HPMC) hydrogel. Using both an implantable glucose sensor and implantable oxygen sensor, we continuously monitored core glucose concentration and oxygen concentration at the centre of hydrogels. We demonstrated that we could tune molecular transport in Si-HPMC hydrogel by changing the polymer concentration. Specifically, the oxygen diffusion coefficient was found to significantly decrease from 3.4×10-10 to 2.4×10-10 m2 s-1 as the polymer concentration increased from 1% to 4% (w/v). Moreover, it was revealed during in vitro culture of cellularized hydrogels that oxygen depletion occurred before glucose depletion, suggesting oxygen diffusion is the major limiting factor for cell survival. Insight was also gained into the mechanism of action by which oxygen and glucose diffuse. Indeed, a direct correlation was found between the average polymer crosslinking node size and glucose parameters, and this correlation was not observed for oxygen. Overall, these experiments provide useful insights for the analysis of nutrient transport and gas exchange in hydrogels and for the development of future cellular microenvironments based on Si-HPMC or similar polysaccharide hydrogels.

Laponite nanoparticle-associated silated hydroxypropylmethyl cellulose as an injectable reinforced interpenetrating network hydrogel for cartilage tissue engineering.

Articular cartilage is a tissue that fails to heal spontaneously. To address this clinically relevant issue, biomaterial-assisted cell therapy is considered promising but often lacks adequate mechanical properties. Our objective was to develop a composite hydrogel using a small amount of nano reinforcement (laponite) capable of gelling within polysaccharide based self-crosslinking hydrogel. This new hybrid construct demonstrates an interpenetrating network (IPN) which enhances the hydrogel mechanical properties without interfering with its cytocompatibility, O2 diffusion and the ability of chondrogenic cells to self-organize in cluster and produce extracellular matrix components. This composite hydrogel may be of relevance for the treatment of cartilage defects and will now be considered in a large animal model of articular cartilage defects.

Polysaccharide Hydrogels Support the Long-Term Viability of Encapsulated Human Mesenchymal Stem Cells and Their Ability to Secrete Immunomodulatory Factors.

While therapeutically interesting, the injection of MSCs suffers major limitations including cell death upon injection and a massive leakage outside the injection site. We proposed to entrap MSCs within spherical particles derived from alginate, as a control, or from silanized hydroxypropyl methylcellulose (Si-HPMC). We developed water in an oil dispersion method to produce small Si-HPMC particles with an average size of about 68 μm. We evidenced a faster diffusion of fluorescein isothiocyanate-dextran in Si-HPMC particles than in alginate ones. Human adipose-derived MSCs (hASC) were encapsulated either in alginate or in Si-HPMC, and the cellularized particles were cultured for up to 1 month. Both alginate and Si-HPMC particles supported cell survival, and the average number of encapsulated hASC per alginate and Si-HPMC particle (7102 and 5100, resp.) did not significantly change. The stimulation of encapsulated hASC with proinflammatory cytokines resulted in the production of IDO, PGE2, and HGF whose concentration was always higher when cells were encapsulated in Si-HPMC particles than in alginate ones. We have demonstrated that Si-HPMC and alginate particles support hASC viability and the maintenance of their ability to secrete therapeutic factors.

A biomaterial-assisted mesenchymal stromal cell therapy alleviates colonic radiation-induced damage.

Healthy tissues surrounding abdomino-pelvic tumours can be impaired by radiotherapy, leading to chronic gastrointestinal complications with substantial mortality. Adipose-derived Mesenchymal Stromal Cells (Ad-MSCs) represent a promising strategy to reduce intestinal lesions. However, systemic administration of Ad-MSCs results in low cell engraftment within the injured tissue. Biomaterials, able to encapsulate and withstand Ad-MSCs, can overcome these limitations. A silanized hydroxypropylmethyl cellulose (Si-HPMC) hydrogel has been designed and characterized for injectable cell delivery using the operative catheter of a colonoscope. We demonstrated that hydrogel loaded-Ad-MSCs were viable, able to secrete trophic factors and responsive to the inflammatory environment. In a rat model of radiation-induced severe colonic damage, Ad-MSC+Si-HPMC improve colonic epithelial structure and hyperpermeability compared with Ad-MSCs injected intravenously or locally. This therapeutic benefit is associated with greater engraftment of Si-HPMC-embedded Ad-MSCs in the irradiated colonic mucosa. Moreover, macrophage infiltration near the injection site was less pronounced when Ad-MSCs were embedded in the hydrogel. Si-HPMC induces modulation of chemoattractant secretion by Ad-MSCs that could contribute to the decrease in macrophage infiltrate. Si-HPMC is suitable for cell delivery by colonoscopy and induces protection of Ad-MSCs in the tissue potentiating their therapeutic effect and could be proposed to patients suffering from colon diseases.

Pharmacologically active microcarriers delivering BDNF within a hydrogel: Novel strategy for human bone marrow-derived stem cells neural/neuronal differentiation guidance and therapeutic secretome enhancement.

Combinatorial tissue engineering strategies for the central nervous system are scarce. We developed and characterized a novel injectable non-toxic stem cell and protein delivery system providing regenerative cues for central nervous system disorders. BDNF, a neurotrophic factor with a wide-range effect, was nanoprecipitated to maintain its structure and released in a sustained manner from novel polymeric microcarriers. The combinatorial 3D support, provided by fibronectin-microcarriers and the hydrogel, to the mesenchymal stem cells guided the cells towards a neuronal differentiation and enhanced their tissue repair properties by promoting growth factors and cytokine secretion. The long-term release of physiological doses of bioactive BDNF, combined to the enhanced secretion of tissue repair factors from the stem cells, constitute a promising therapeutic approach.

Preparation, characterization, and in-vitro performance of novel injectable silanized-hydroxypropyl methylcellulose/phase-transformed calcium phosphate composite bone cements

Silanized-hydroxypropyl methylcellulose(Si-HPMC)/phase-transformed calcium phosphate (PTCP) composite cements were successfully prepared for application as novel injectable bone cements with enhanced biocompatibility. The crystal structure and chemical state of the synthesized PTCP and Si-HPMC powders as solid and liquid phases of the composite cements were determined via X-ray diffraction and Fourier transform infrared spectroscopy. The physical handling and mechanical properties of the Si-HPMC/PTCP composite calcium phosphate cements (CPCs) were measured via viscometric analysis, injectability tests, and using a universal testing machine. The cytotoxicity of the Si-HPMC/PTCP composite CPCs was evaluated and compared with that of Si-HPMC/α-TCP as a control. Analysis of the in-vitro mechanical properties of the Si-HPMC/PTCP composite CPCs showed that hardening was an inherent function of the cements after immersion in Hanks' balanced salt solution. The Si-HPMC/PTCP composite CPCs exhibited better biocompatibility and injectability than Si-HPMC/α-TCP; however, the Si-HPMC/PTCP composite CPCs have relatively lower mechanical properties than Si-HPMC/α-TCP. Therefore, these novel injectable cements can potentially be used as calcium phosphate cements for biomedical applications.

Assessment and Quantification of Noncollagenic Matrix Proteins Released from Human Dentin Powder Incorporated into a Silated Hydroxypropylmethylcellulose Biomedical Hydrogel

IntroductionThe dentin extracellular matrix is a reservoir of bioactive molecules sequestered into dentin during dental initial development. They can be released under pathological conditions but also by controlled demineralization with bioactive materials. The purpose of this study was to investigate the ability of a biomedical hydrogel to extract and release these proteins from smashed dentin. MethodsSmashed dentin was obtained with 2 different kinds of grinders: a blade mill and a zirconia mortar grinder. The particle size was measured by scanning electron microscopy. Dentin powder was incorporated into a silated hydroxypropylmethylcellulose hydrogel. Several types of mixtures with variable parameters were tested. The mixtures were immersed into phosphate-buffered saline. The supernatants were collected, and the total released proteins were quantified by gel shift migration and Coomassie staining. The presence of transforming growth factor beta 1 was investigated by Western blot analysis and the ELISA. ResultsThe mixture dentin powder/hydrogel released proteins (from 49.1 μg/mL–137.9 μg/mL according to the mixtures). The release kinetics was growing and started from the first day until stabilization at 14 days. The quantity of released proteins was directly related to the size of the particles and the weight of the powder incorporated into the hydrogel. Gel shift with direct revelation by ultraviolet and Western blot analyses confirmed the presence of transforming growth factor beta 1 using ELISA. ConclusionsWe showed that silated hydroxypropylmethylcellulose hydrogel was able to extract dentin matrix proteins from smashed dentin powder. This mixture could be considered a new way of dental treatment for the dentin-pulp complex and bone regeneration.

Interpenetrated Si-HPMC/alginate hydrogels as a potential scaffold for human tissue regeneration.

Interpenetrated gels of biocompatible polysaccharides alginate and silanized hydroxypropyl methyl cellulose (Si-HPMC) have been studied in order to assess their potential as scaffolds for the regeneration of human tissues. Si-HPMC networks were formed by reduction of the pH to neutral and alginate networks were formed by progressive in situ release of Ca(2+). Linear and non-linear mechanical properties of the mixed gels at different polymer and calcium concentrations were compared with those of the corresponding single gels. The alginate/Si-HPMC gels were found to be stiffer than pure Si-HPMC gels, but weaker and more deformable than pure alginate gels. No significant difference was found for the maximum stress at rupture measured during compression for all these gels. The degrees of swelling or contraction in excess water at pH 7 as well as the release of Ca(2+) was measured as a function of time. Pure alginate gels contracted by as much as 50 % and showed syneresis, which was much reduced or even eliminated for mixed gels. The important release of Ca(2+) upon ageing for pure alginate gels was much reduced for the mixed gels. Furthermore, results of cytocompatibility assays indicated that there was no cytotoxicity of Si-HPMC/alginate hydrogels in 2D and 3D culture of human SW1353 cells. The results show that using interpenetrated Si-HPMC/alginate gels has clear advantages over the use of single gels for application in tissue regeneration.

AFM observation of Si-HPMC hydrogel cross-linking

Event Abstract Back to Event AFM observation of Si-HPMC hydrogel cross-linking Fabienne Jordana1, 2, 3, Hassan Saadaoui4, 5, Khalid Khairoun1, Jean-Marc Olive6 and Pierre Weiss1, 2, 3 1 INSERM, LIOAD, U S 791 INSERM, France 2 University of Nantes, Faculty of Dentistry, France 3 CHU of Nantes, France 4 CNRS, Paul Pascal Research Center (CRPP), UPR 8641, France 5 University of Bordeaux, France 6 CNRS, I2M, UMR 5295, France Introduction: Silated hydroxypropylmethylcellulose (Si-HPMC) is an injectable and self-setting hydrogel used as a three-dimensional synthetic matrix for tissue engineering. Si-HPMC is a gel based on a derivate from HPMC, a cellulose derivative polymer. This biocompatible polysaccharide forms a covalently crosslinked hydrogel due to silanol condensation[1]-[3]. Materials and Methods: A thin layer of Si-HPMC hydrogel disks was transferred to a freshly cleaved mica surface. The Si-HPMC hydrogel was applied to the top surface of the mica. Images of Si-HPMC hydrogel were obtained by atomic force microscopy (AFM) (Bruker© Icon, 2010). During 24 hours, Si-HPMC hydrogel surface was observed. The thin hydrogel layer adhering to the mica surface was scanned with the AFM operating in tapping mode using an etched single crystal silicon probe. The drive frequency, amplitude, gains, and amplitude set point ratio were adjusted to give height and phase images with the clearest image details. AFM (height and phase shift) images analysis and examination in Fourier transformed operation mode were performed with the software NanoScope Analysis 1.30 (Bruker Corporation©, 2011). Results and Discussion: Polymerization and cross-linking of the polymer begin in the first seconds and continue during the whole time of observation. Height and phase shift images reflect the surface topography and relative mechanical responses of the sample, respectively. Images demonstrated a network-like structure with pores. The gels consisted of branched structures where the branch points may be interpreted as points where junctions between silanol cross-linked chains occur. The nanosized pore range from approximately 10-20 nm. Some of the pores were interconnected. Surface topography and relative mechanical responses regularly changes over time (fig. 1 and fig. 2). Fig. 1: AFM phase image of Si-HPMC hydrogel layer, after 30 minutes of AFM scanning. Scale is 1µm. Fig. 2: AFM phase image of Si-HPMC hydrogel layer, after 7 hours of AFM scanning. Scale is 1µm. The network becomes more complex with time. Examination of AFM images, in Fourier transformed operation mode of tapping mode-AFM, revealed that Si-HPMC hydrogel is characterized by an isotropic structure. Conclusion: These images revealed for the first time how the network is organized within Si-HPMC hydrogel and demonstrated that Si-HPMC hydrogel is characterized by an isotropic structure.

A simple and effective approach to prepare injectable macroporous calcium phosphate cement for bone repair: Syringe-foaming using a viscous hydrophilic polymeric solution

In this study, we propose a simple and effective strategy to prepare injectable macroporous calcium phosphate cements (CPCs) by syringe-foaming via hydrophilic viscous polymeric solution, such as using silanized-hydroxypropyl methylcellulose (Si-HPMC) as a foaming agent. The Si-HPMC foamed CPCs demonstrate excellent handling properties such as injectability and cohesion. After hardening the foamed CPCs possess hierarchical macropores and their mechanical properties (Young’s modulus and compressive strength) are comparable to those of cancellous bone. Moreover, a preliminary in vivo study in the distal femoral sites of rabbits was conducted to evaluate the biofunctionality of this injectable macroporous CPC. The evidence of newly formed bone in the central zone of implantation site indicates the feasibility and effectiveness of this foaming strategy that will have to be optimized by further extensive animal experiments. Statement of significanceA major challenge in the design of biomaterial-based injectable bone substitutes is the development of cohesive, macroporous and self-setting calcium phosphate cement (CPC) that enables rapid cell invasion with adequate initial mechanical properties without the use of complex processing and additives. Thus, we propose a simple and effective strategy to prepare injectable macroporous CPCs through syringe-foaming using a hydrophilic viscous polymeric solution (silanized-hydroxypropyl methylcellulose, Si-HPMC) as a foaming agent, that simultaneously meets all the aforementioned aims. Evidence from our in vivo studies shows the existence of newly formed bone within the implantation site, indicating the feasibility and effectiveness of this foaming strategy, which could be used in various CPC systems using other hydrophilic viscous polymeric solutions.

Functionalisation of Polysaccharides for the Purposes of Electrospinning: A Case Study Using HPMC and Si-HPMC.

Hydrogels are a suitable scaffold material for a variety of tissue engineering applications. However, these materials have a weak structure and require reinforcement. Integrating electrospun fibers could strengthen material properties. This study created fibers and evaluated the influence of the presence of polar head groups within a polysaccharide backbone following functionalization: silated-hydroxypropyl methylcellulose (Si-HPMC). Electrospinning is a multi-parameter, step by step process that requires optimization of solution and process parameters to understand and control the process. Fibers were created for 2%–3% wt/v solutions in water and ethanol. Viscosities of solutions were correlated with spinnability. Variations on process parameters did not reveal major variation on fiber morphology. Once controlled, the process was used for HPMC/Si-HPMC mixture solutions. Solubilization and dilution of Si-HPMC were made with common solvents for electrospinning. Two forms of polymer conformation were electrospun: silanol ending and silanolate ending. Microstructures and resulting nanofibers were analyzed by scanning electron microscopy (SEM) and Energy Dispersive Analysis (EDX). The results show the feasibility of our strategy for creating nanofibers and the influence of polar head groups on electrospinnability.

Enriching a cellulose hydrogel with a biologically active marine exopolysaccharide for cell-based cartilage engineering.

The development of biologically and mechanically competent hydrogels is a prerequisite in cartilage engineering. We recently demonstrated that a marine exopolysaccharide, GY785, stimulates the in vitro chondrogenesis of adipose stromal cells. In the present study, we thus hypothesized that enriching our silated hydroxypropyl methylcellulose hydrogel (Si-HPMC) with GY785 might offer new prospects in the development of scaffolds for cartilage regeneration. The interaction properties of GY785 with growth factors was tested by surface plasmon resonance (SPR). The biocompatibility of Si-HPMC/GY785 towards rabbit articular chondrocytes (RACs) and its ability to maintain and recover a chondrocytic phenotype were then evaluated in vitro by MTS assay, cell counting and qRT-PCR. Finally, we evaluated the potential of Si-HPMC/GY785 associated with RACs to form cartilaginous tissue in vivo by transplantation into the subcutis of nude mice for 3 weeks. Our SPR data indicated that GY785 was able to physically interact with BMP-2 and TGFβ. Our analyses also showed that three-dimensionally (3D)-cultured RACs into Si-HPMC/GY785 strongly expressed type II collagen (COL2) and aggrecan transcripts when compared to Si-HPMC alone. In addition, RACs also produced large amounts of extracellular matrix (ECM) containing glycosaminoglycans (GAG) and COL2. When dedifferentiated RACs were replaced in 3D in Si-HPMC/GY785, the expressions of COL2 and aggrecan transcripts were recovered and that of type I collagen decreased. Immunohistological analyses of Si-HPMC/GY785 constructs transplanted into nude mice revealed the production of a cartilage-like extracellular matrix (ECM) containing high amounts of GAG and COL2. These results indicate that GY785-enriched Si-HPMC appears to be a promising hydrogel for cartilage tissue engineering. Copyright © 2015 John Wiley & Sons, Ltd.