Knowledge and Practice Behaviours of Obstetricians/Gynecologists and Midwives Concerning Periodontal Health and Pregnancy.

PURPOSE: The purpose of the present study was to evaluate the level of knowledge of prenatal health professionals concerning the relationship between periodontal diseases and pregnancy complications, as well as their professional implications in the oral health field. MATERIALS AND METHODS: A questionnaire was distributed to obstetricians/gynecologists, interns specialised in obstetrics/gynecology, midwives, and student midwives at Loire Atlantique and Vendée hospitals (France). The questionnaire included 5 sociodemographic questions and 14 questions regarding the level of knowledge about the relationship between periodontal diseases and pregnancy complications as well as the professionals' level of involvement in oral health care. RESULTS: Twenty-three obstetricians/gynecologists and 55 midwives responded to the questionnaire. Preterm delivery and chorioamnionitis were the most frequently mentioned complications of pregnancy, whereas the risk of pre-eclampsia was rarely mentioned. Half of the professionals said they were aware of the oral manifestations of pregnancy. Gingivitis and an increased risk of caries were the most frequently mentioned items, whereas epulis was the least frequently mentioned item. The level of involvement of prenatal care practitioners in oral health care was limited due to a lack of competence and time. Nevertheless, 64% of the participants discussed the risks of poor oral hygiene with their patients. CONCLUSION: There is good knowledge among French gynecologists/obstetricians and midwives regarding the oral manifestations of pregnancy. However, there is still a lack of knowledge concerning the links between periodontal diseases and pregnancy complications. The involvement and behaviour of pregnancy professionals in the oral health field is inadequate. The present survey highlights the need to improve the initial and continuing education of obstetricians and midwives on this topic.

Sustainable Biomass Lignin-Based Hydrogels: A Review on Properties, Formulation, and Biomedical Applications.

Different techniques have been developed to overcome the recalcitrant nature of lignocellulosic biomass and extract lignin biopolymer. Lignin has gained considerable interest owing to its attractive properties. These properties may be more beneficial when including lignin in the preparation of highly desired value-added products, including hydrogels. Lignin biopolymer, as one of the three major components of lignocellulosic biomaterials, has attracted significant interest in the biomedical field due to its biocompatibility, biodegradability, and antioxidant and antimicrobial activities. Its valorization by developing new hydrogels has increased in recent years. Furthermore, lignin-based hydrogels have shown great potential for various biomedical applications, and their copolymerization with other polymers and biopolymers further expands their possibilities. In this regard, lignin-based hydrogels can be synthesized by a variety of methods, including but not limited to interpenetrating polymer networks and polymerization, crosslinking copolymerization, crosslinking grafted lignin and monomers, atom transfer radical polymerization, and reversible addition-fragmentation transfer polymerization. As an example, the crosslinking mechanism of lignin-chitosan-poly(vinyl alcohol) (PVA) hydrogel involves active groups of lignin such as hydroxyl, carboxyl, and sulfonic groups that can form hydrogen bonds (with groups in the chemical structures of chitosan and/or PVA) and ionic bonds (with groups in the chemical structures of chitosan and/or PVA). The aim of this review paper is to provide a comprehensive overview of lignin-based hydrogels and their applications, focusing on the preparation and properties of lignin-based hydrogels and the biomedical applications of these hydrogels. In addition, we explore their potential in wound healing, drug delivery systems, and 3D bioprinting, showcasing the unique properties of lignin-based hydrogels that enable their successful utilization in these areas. Finally, we discuss future trends in the field and draw conclusions based on the findings presented.

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.

Injectable silanized hyaluronic acid hydrogel/biphasic calcium phosphate granule composites with improved handling and biodegradability promote bone regeneration in rabbits.

Biphasic calcium phosphate (BCP) granules are osteoconductive biomaterials used in clinics to favor bone reconstruction. Yet, poor cohesivity, injectability and mechanical properties restrain their use as bone fillers. In this study, we incorporated BCP granules into in situ forming silanized hyaluronic acid (Si-HA) and hydroxypropylmethylcellulose (Si-HPMC) hydrogels. Hydrogel composites were shown to be easily injectable (F < 30 N), with fast hardening properties (<5 min), and similar mechanical properties (E∼ 60 kPa). In vivo, both hydrogels were well tolerated by the host, but showed different biodegradability with Si-HA gels being partially degraded after 21d, while Si-HPMC gels remained stable. Both composites were easily injected into critical size rabbit defects and remained cohesive. After 4 weeks, Si-HPMC/BCP led to poor bone healing due to a lack of degradation. Conversely, Si-HA/BCP composites were fully degraded and beneficially influenced bone regeneration by increasing the space available for bone ingrowth, and by accelerating BCP granules turnover. Our study demonstrates that the degradation rate is key to control bone regeneration and that Si-HA/BCP composites are promising biomaterials to regenerate bone defects.

Combination of bone substitutes and vectors in periodontology and implantology: A systematic review.

The aim of the systematic review was to analyze the use of combination of bone substitutes and vectors in periodontology and implantology among animals models and humans. Electronic databases were searched, and additional hand search was performed. The research strategy was achieved according to the PRISMA guidelines. The including criteria were: combination of bone substitutes and vectors, in vivo studies, a precise number of specimens, histological and radiographic analysis, written in English. The risk of bias was evaluated for individual studies. Thirty-two articles were selected and investigated in this systematic review. The results do not show a superiority of the use of composite biomaterial in comparison with simple biomaterial but suggest the efficacity of their utilization as a carrier of bioactive agents. Future studies need to identify the suitable association of bone substitutes and vectors and explore interest in their use such as the support of growth factors.

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 Forming, Silanized Hyaluronic Acid Hydrogels with Fine Control Over Mechanical Properties and In Vivo Degradation for Tissue Engineering Applications.

In situ forming hydrogels that can be injected into tissues in a minimally-invasive fashion are appealing as delivery vehicles for tissue engineering applications. Ideally, these hydrogels should have mechanical properties matching those of the host tissue, and a rate of degradation adapted for neo-tissue formation. Here, the development of in situ forming hyaluronic acid hydrogels based on the pH-triggered condensation of silicon alkoxide precursors into siloxanes is reported. Upon solubilization and pH adjustment, the low-viscosity precursor solutions are easily injectable through fine-gauge needles prior to in situ gelation. Tunable mechanical properties (stiffness from 1 to 40 kPa) and associated tunable degradability (from 4 days to more than 3 weeks in vivo) are obtained by varying the degree of silanization (from 4.3% to 57.7%) and molecular weight (120 and 267 kDa) of the hyaluronic acid component. Following cell encapsulation, high cell viability (> 80%) is obtained for at least 7 days. Finally, the in vivo biocompatibility of silanized hyaluronic acid gels is verified in a subcutaneous mouse model and a relationship between the inflammatory response and the crosslink density is observed. Silanized hyaluronic acid hydrogels constitute a tunable hydrogel platform for material-assisted cell therapies and tissue engineering applications.

A Self-Setting Hydrogel of Silylated Chitosan and Cellulose for the Repair of Osteochondral Defects: From in vitro Characterization to Preclinical Evaluation in Dogs.

Articular cartilage (AC) may be affected by many injuries including traumatic lesions that predispose to osteoarthritis. Currently there is no efficient cure for cartilage lesions. In that respect, new strategies for regenerating AC are contemplated with interest. In this context, we aim to develop and characterize an injectable, self-hardening, mechanically reinforced hydrogel (Si-HPCH) composed of silanised hydroxypropymethyl cellulose (Si-HPMC) mixed with silanised chitosan. The in vitro cytocompatibility of Si-HPCH was tested using human adipose stromal cells (hASC). In vivo, we first mixed Si-HPCH with hASC to observe cell viability after implantation in nude mice subcutis. Si-HPCH associated or not with canine ASC (cASC), was then tested for the repair of osteochondral defects in canine femoral condyles. Our data demonstrated that Si-HPCH supports hASC viability in culture. Moreover, Si-HPCH allows the transplantation of hASC in the subcutis of nude mice while maintaining their viability and secretory activity. In the canine osteochondral defect model, while the empty defects were only partially filled with a fibrous tissue, defects filled with Si-HPCH with or without cASC, revealed a significant osteochondral regeneration. To conclude, Si-HPCH is an injectable, self-setting and cytocompatible hydrogel able to support the in vitro and in vivo viability and activity of hASC as well as the regeneration of osteochondral defects in dogs when implanted alone or with ASC.

Heparan Sulfate Mimetics: A New Way to Optimize Therapeutic Effects of Hydrogel-Embedded Mesenchymal Stromal Cells in Colonic Radiation-Induced Damage.

Clinical expression of gastrointestinal radiation toxicity on non-cancerous tissue could be very life threatening and clinicians must deal increasingly with the management of late side effects of radiotherapy. Cell therapy, in particular mesenchymal stromal cell (MSC) therapy, has shown promising results in numerous preclinical animal studies and thus has emerged as a new hope for patient refractory to current treatments. However, many stem cell clinical trials do not confer any beneficial effect suggesting a real need to accelerate research towards the successful clinical application of stem cell therapy. In this study, we propose a new concept to improve the procedure of MSC-based treatment for greater efficacy and clinical translatability. We demonstrated that heparan sulfate mimetic (HS-m) injections that restore the extracellular matrix network and enhance the biological activity of growth factors, associated with local injection of MSC protected in a hydrogel, that increase cell engraftment and cell survival, improve the therapeutic benefit of MSC treatment in two animal models relevant of the human pathology. For the first time, a decrease of the injury score in the ulcerated area was observed with this combined treatment. We also demonstrated that the combined treatment favored the epithelial regenerative process. In this study, we identified a new way, clinically applicable, to optimize stem-cell therapy and could be proposed to patients suffering from severe colonic defect after radiotherapy.

Evaluation of a hydrogel membrane on bone regeneration in furcation periodontal defects in dogs.

The aim of the study was to evaluate bone regeneration using a canine model with surgically created periodontal defects filled for 12 weeks using a stratified biomaterial consisting in a biphasic calcium phosphate (BCP) covered with a crosslinking hydrogel acting as polymer membrane of silated hydroxypropyl methylcellulose (Si-HPMC) as the tested new concept. Bilateral, critical-sized, defects were surgically created at the mandibular premolar teeth of six adult beagle dogs. The defects were randomly allocated and: (i) left empty for spontaneous healing or filled with: (ii) BCP and a collagen membrane; (iii) BCP and hydrogel Si-HPMC membrane. At 12 weeks, the experimental conditions resulted in significantly enhanced bone regeneration in the test BCP/Si-HPMC group. Within the limits of this study, we suggest that the hydrogel Si-HPMC may act as an occlusive barrier to protect bone area from soft connective tissue invasion and then effectively contribute to enhance bone regeneration.

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.

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

Articular cartilage is a connective tissue which does not spontaneously heal. To address this issue, biomaterial-assisted cell therapy has been researched with promising advances. The lack of strong mechanical properties is still a concern despite significant progress in three-dimensional scaffolds. This article's objective was to develop a composite hydrogel using a small amount of nano-reinforcement clay known as laponites. These laponites were capable of self-setting within the gel structure of the silated hydroxypropylmethyl cellulose (Si-HPMC) hydrogel. Laponites (XLG) were mixed with Si-HPMC to prepare composite hydrogels leading to the development of a hybrid interpenetrating network. This interpenetrating network increases the mechanical properties of the hydrogel. The in vitro investigations showed no side effects from the XLG regarding cytocompatibility or oxygen diffusion within the composite after cross-linking. The ability of the hybrid scaffold containing the composite hydrogel and chondrogenic cells to form a cartilaginous tissue in vivo was investigated during a 6-week implantation in subcutaneous pockets of nude mice. Histological analysis of the composite constructs revealed the formation of a cartilage-like tissue with an extracellular matrix containing glycosaminoglycans and collagens. Overall, this new hybrid construct demonstrates an interpenetrating network which enhances the hydrogel mechanical properties without interfering with its cytocompatibility, oxygen diffusion, or the ability of chondrogenic cells to self-organize in the cluster and produce extracellular matrix components. This composite hydrogel may be of relevance for the treatment of cartilage defects in a large animal model of articular cartilage defects. STATEMENT OF SIGNIFICANCE: 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.

Toward the development of biomimetic injectable and macroporous biohydrogels for regenerative medicine.

Repairing or replacing damaged human tissues has been the ambitious goal of regenerative medicine for over 25years. One promising approach is the use of hydrated three-dimensional scaffolds, known as hydrogels, which have had good results repairing tissues in pre-clinical trials. Benefiting from breakthrough advances in the field of biology, and more particularly regarding cell/matrix interactions, these hydrogels are now designed to recapitulate some of the fundamental cues of native environments to drive the local tissue regeneration. We highlight the key parameters that are required for the development of smart and biomimetic hydrogels. We also review the wide variety of polymers, crosslinking methods, and manufacturing processes that have been developed over the years. Of particular interest is the emergence of supramolecular chemistries, allowing for the development of highly functional and reversible biohydrogels. Moreover, advances in computer assisted design and three-dimensional printing have revolutionized the production of macroporous hydrogels and allowed for more complex designs than ever before with the opportunity to develop fully reconstituted organs. Today, the field of biohydrogels for regenerative medicine is a prolific area of research with applications for most bodily tissues. On top of these applications, injectable hydrogels and macroporous hydrogels (foams) were found to be the most successful. While commonly associated with cells or biologics as drug delivery systems to increase therapeutic outcomes, they are steadily being used in the emerging fields of organs-on-chip and hydrogel-assisted cell therapy. To highlight these advances, we review some of the recent developments that have been achieved for the regeneration of tissues, focusing on the articular cartilage, bone, cardiac, and neural tissues. These biohydrogels are associated with improved cartilage and bone defects regeneration, reduced left ventricular dilation upon myocardial infarction and display promising results repairing neural lesions. Combining the benefits from each of these areas reviewed above, we envision that an injectable biohydrogel foam loaded with either stem cells or their secretome is the most promising hydrogel solution to trigger tissue regeneration. A paradigm shift is occurring where the combined efforts of fundamental and applied sciences head toward the development of hydrogels restoring tissue functions, serving as drug screening platforms or recreating complex organs.

Microgels of silylated HPMC as a multimodal system for drug co-encapsulation.

Combined therapy is a global strategy developed to prevent drug resistance in cancer and infectious diseases. In this field, there is a need of multifunctional drug delivery systems able to co-encapsulate small drug molecules, peptides, proteins, associated to targeting functions, nanoparticles. Silylated hydrogels are alkoxysilane hybrid polymers that can be engaged in a sol-gel process, providing chemical cross linking in physiological conditions, and functionalized biocompatible hybrid materials. In the present work, microgels were prepared with silylated (hydroxypropyl)methyl cellulose (Si-HPMC) that was chemically cross linked in soft conditions of pH and temperature. They were prepared by an emulsion templating process, water in oil (W/O), as microreactors where the condensation reaction took place. The ability to functionalize the microgels, so-called FMGs, in a one-pot process, was evaluated by grafting a silylated hydrophilic model drug, fluorescein (Si-Fluor), using the same reaction of condensation. Biphasic microgels (BPMGs) were prepared to evaluate their potential to encapsulate lipophilic model drug (Nile red). They were composed of two separate compartments, one oily phase (sesame oil) trapped in the cross linked Si-HPMC hydrophilic phase. The FMGs and BPMGs were characterized by different microscopic techniques (optic, epi-fluorescence, Confocal Laser Scanning Microscopy and scanning electronic microscopy), the mechanical properties were monitored using nano indentation by Atomic Force Microscopy (AFM), and different preliminary tests were performed to evaluate their chemical and physical stability. Finally, it was demonstrated that it is possible to co-encapsulate both hydrophilic and hydrophobic drugs, in silylated microgels, that were physically and chemically stable. They were obtained by chemical cross linking in soft conditions, and without surfactant addition during the emulsification process. The amount of drug loaded was in favor of further biological activity. Mechanical stimulations should be necessary to trigger drug release.

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.

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.

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 SIGNIFICANCE: A 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.

Interplay of thermal and covalent gelation of silanized hydroxypropyl methyl cellulose gels.

Silanized hydroxypropyl methyl cellulose (Si-HPMC) is a biocompatible polysaccharide that forms a covalently crosslinked hydrogel at all temperatures due to silanol condensation. Unmodified HPMC forms reversible turbid physical gels when heated above 55°C. The interaction between thermal gelation and covalent crosslinking of Si-HPMC was investigated with rheology, turbidity and microscopy. Thermal gelation of the HPMC backbone was found to reinforce Si-HPMC gels at room temperature. However, simultaneous thermal and covalent crosslinking at higher temperatures led to weaker turbid gels at room temperature. The effect of the pH and the addition of orthophosphate on the elastic modulus and the gelation kinetics was investigated.

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.