Immunomodulation Using BMP-7 and IL-10 to Enhance the Mineralization Capacity of Bone Progenitor Cells in a Fracture Hematoma-Like Environment.

Following biomaterial implantation, a failure to resolve inflammation during the formation of a fracture hematoma can significantly limit the biomaterial's ability to facilitate bone regeneration. This study aims to combine the immunomodulatory and osteogenic effects of BMP-7 and IL-10 with the regenerative capacity of collagen-hydroxyapatite (CHA) scaffolds to enhance in vitro mineralization in a hematoma-like environment. Incubation of CHA scaffolds with human whole blood leads to rapid adsorption of fibrinogen, significant stiffening of the scaffold, and the formation of a hematoma-like environment characterized by a limited capacity to support the infiltration of human bone progenitor cells, a significant upregulation of inflammatory cytokines and acute phase proteins, and significantly reduced osteoconductivity. CHA scaffolds functionalized with BMP-7 and IL-10 significantly downregulate the production of key inflammatory cytokines, including IL-6, IL-8, and leptin, creating a more permissive environment for mineralization, ultimately enhancing the biomaterial's osteoconductivity. In conclusion, targeting the onset of inflammation in the early phase of bone healing using BMP-7 and IL-10 functionalized CHA scaffolds is a promising approach to effectively downregulate inflammatory processes, while fostering a more permissive environment for bone regeneration.

The Effect of Substrate Properties on Cellular Behavior and Nanoparticle Uptake in Human Fibroblasts and Epithelial Cells.

The delivery of nanomedicines into cells holds enormous therapeutic potential; however little is known regarding how the extracellular matrix (ECM) can influence cell-nanoparticle (NP) interactions. Changes in ECM organization and composition occur in several pathophysiological states, including fibrosis and tumorigenesis, and may contribute to disease progression. We show that the physical characteristics of cellular substrates, that more closely resemble the ECM in vivo, can influence cell behavior and the subsequent uptake of NPs. Electrospinning was used to create two different substrates made of soft polyurethane (PU) with aligned and non-aligned nanofibers to recapitulate the ECM in two different states. To investigate the impact of cell-substrate interaction, A549 lung epithelial cells and MRC-5 lung fibroblasts were cultured on soft PU membranes with different alignments and compared against stiff tissue culture plastic (TCP)/glass. Both cell types could attach and grow on both PU membranes with no signs of cytotoxicity but with increased cytokine release compared with cells on the TCP. The uptake of silica NPs increased more than three-fold in fibroblasts but not in epithelial cells cultured on both membranes. This study demonstrates that cell-matrix interaction is substrate and cell-type dependent and highlights the importance of considering the ECM and tissue mechanical properties when designing NPs for effective cell targeting and treatment.

3D-Printed Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)-Cellulose-Based Scaffolds for Biomedical Applications.

While biomaterials have become indispensable for a wide range of tissue repair strategies, second removal procedures oftentimes needed in the case of non-bio-based and non-bioresorbable scaffolds are associated with significant drawbacks not only for the patient, including the risk of infection, impaired healing, or tissue damage, but also for the healthcare system in terms of cost and resources. New biopolymers are increasingly being investigated in the field of tissue regeneration, but their widespread use is still hampered by limitations regarding mechanical, biological, and functional performance when compared to traditional materials. Therefore, a common strategy to tune and broaden the final properties of biopolymers is through the effect of different reinforcing agents. This research work focused on the fabrication and characterization of a bio-based and bioresorbable composite material obtained by compounding a poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBH) matrix with acetylated cellulose nanocrystals (CNCs). The developed biocomposite was further processed to obtain three-dimensional scaffolds by additive manufacturing (AM). The 3D printability of the PHBH-CNC biocomposites was demonstrated by realizing different scaffold geometries, and the results of in vitro cell viability studies provided a clear indication of the cytocompatibility of the biocomposites. Moreover, the CNC content proved to be an important parameter in tuning the different functional properties of the scaffolds. It was demonstrated that the water affinity, surface roughness, and in vitro degradability rate of biocomposites increase with increasing CNC content. Therefore, this tailoring effect of CNC can expand the potential field of use of the PHBH biopolymer, making it an attractive candidate for a variety of tissue engineering applications.

Growth factor-loaded sulfated microislands in granular hydrogels promote hMSCs migration and chondrogenic differentiation.

Cell-based therapies for articular cartilage lesions are expensive and time-consuming; clearly, a one-step procedure to induce endogenous repair would have significant clinical benefits. Acellular heterogeneous granular hydrogels were explored for their injectability, cell-friendly cross-linking, and ability to promote migration, as well as to serve as a scaffold for depositing cartilage extracellular matrix. The hydrogels were prepared by mechanical sizing of bulk methacrylated hyaluronic acid (HAMA) and bulk HAMA incorporating sulfated HAMA (SHAMA). SHAMA's negative charges allowed for the retention of positively charged growth factors (GFs) (e.g., TGFB3 and PDGF-BB). Mixtures of HAMA and GF-loaded SHAMA microgels were annealed by enzymatic cross-linking, forming heterogeneous granular hydrogels with GF deposits. The addition of GF loaded sulfated microislands guided cell migration and enhanced chondrogenesis. Granular heterogeneous hydrogels showed increased matrix deposition and cartilage tissue maturation compared to bulk or homogeneous granular hydrogels. This advanced material provides an ideal 3D environment for guiding cell migration and differentiation into cartilage. STATEMENT OF SIGNIFICANCE: Acellular materials which promote regeneration are of great interest for repair of cartilage defects, and they are more cost- and time-effective compared to current cell-based therapies. Here we develop an injectable, granular hydrogel system which promotes cell migration from the surrounding tissue, facilitating endogenous repair. The hydrogel architecture and chemistry were optimized to increase cell migration and extracellular matrix deposition. The present study provides quantitative data on the effect of microgel size and chemical modification on cell migration, growth factor retention and tissue maturation.

In Situ Investigation of Pseudomonas aeruginosa Biofilm Development: Interplay between Flow, Growth Medium, and Mechanical Properties of Substrate.

To better understand the impact of biomaterial mechanical properties and growth medium on bacterial adhesion and biofilm formation under flow, we investigated the biofilm formation ability of Pseudomonas aeruginosa in different media on polydimethylsiloxane (PDMS) of different stiffness in real time using a microfluidic platform. P. aeruginosa colonization was recorded with optical microscopy and automated image analysis. The bacterial intracellular level of cyclic diguanylate (c-di-GMP), which regulates biofilm formation, was monitored using the transcription of the putative adhesin gene (cdrA) as a proxy. Contrary to the previous supposition, we revealed that PDMS material stiffness within the tested range has negligible impact on biofilm development and biofilm structures, whereas culture media not only influence the kinetics of biofilm development but also affect the biofilm morphology and structure dramatically. Interestingly, magnesium rather than previously reported calcium was identified here to play a decisive role in the formation of dense P. aeruginosa aggregates and high levels of c-di-GMP. These results demonstrate that although short-term adhesion assays bring valuable insight into bacterial and material interactions, long-term evaluations are essential to better predict overall biofilm outcome. The microfluidic system developed here presents a valuable application potential for studying biofilm development in situ. .

Uncoupling bacterial attachment on and detachment from polydimethylsiloxane surfaces through empirical and simulation studies.

Bacterial infections related to medical devices can cause severe problems, whose solution requires in-depth understanding of the interactions between bacteria and surfaces. This work investigates the influence of surface physicochemistry on bacterial attachment and detachment under flow through both empirical and simulation studies. We employed polydimethylsiloxane (PDMS) substrates having different degrees of crosslinking as the model material and the extended Derjaguin - Landau - Verwey - Overbeek model as the simulation method. Experimentally, the different PDMS materials led to similar numbers of attached bacteria, which can be rationalized by the identical energy barriers simulated between bacteria and the different materials. However, different numbers of residual bacteria after detachment were observed, which was suggested by simulation that the detachment process is determined by the interfacial physicochemistry rather than the mechanical property of a material. This finding is further supported by analyzing the bacteria detachment from PDMS substrates from which non-crosslinked polymer chains had been removed: similar numbers of residual bacteria were found on the extracted PDMS substrates. The knowledge gained in this work can facilitate the projection of bacterial colonization on a given surface.

Photo-activated titanium surface confers time dependent bactericidal activity towards Gram positive and negative bacteria.

Titanium (Ti)-based implants are broadly applied in the medical field, but their related infections can lead to implant failure. Photo-irradiation of metal materials to generate antimicrobial agents, an alternative to antibiotics, is a promising method to reduce bacterial infection and antibiotic usage. It is therefore important to understand how bacterial pathogens respond to Ti surfaces. Here, Gram-negative Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus, the most prevalent pathogens linked to healthcare-associated infections, were used as model strains. Two different kinds of Ti surfaces respectively stored in dry condition and 0.9 % NaCl solution were applied. Upon UV irradiation and in the absence of bacteria, both tested surfaces exhibited similar bactericidal activity, even though the surfaces stored in 0.9 % NaCl solution generated a slightly higher level of reactive oxygen species (ROS). Interestingly, P. aeruginosa and S. aureus responded to the irradiated Ti surfaces differently regarding interaction time: the number of viable P. aeruginosa was reduced up to 90 % after 30 min interaction with the treated surfaces compared to the untreated ones, but this reduction is lessened to 69 %-81 % after 240 min. By contrast, UV treatment of surfaces did not impact the viability of S. aureus after 30 min interaction, however, led to more than 99 % reduction after 240 min incubation. These results provide first experimental evidence that Gram negative and positive bacterial species respond to ROS with different inactivation kinetics. This work also demonstrated that treatment with photo-irradiation in the absence of bacteria conferred Ti surfaces with efficient bactericidal activity.

Virus pH-Dependent Interactions with Cationically Modified Cellulose and Their Application in Water Filtration.

Norovirus and Rotavirus are among the pathogens causing a large number of disease outbreaks due to contaminated water. These viruses are nanoscale particles that are difficult to remove by common filtration approaches which are based on physical size exclusion, and require adsorption-based filtration methods. This study reports the pH-responsive interactions of viruses with cationic-modified nanocellulose and demonstrates a filter material that adsorbs nanoscale viruses and can be regenerated by changing the solution's pH. The bacteria viruses Qbeta and MS2, with diameters below 30 nm but different surface properties, are used to evaluate the pH-dependency of the interactions and the filtration process. Small angle X-ray scattering, cryogenic transmission electron microscopy, and ζ-potential measurements are used to study the interactions and analyze changes in their nanostructure and surface properties of the virus upon adsorption. The virus removal capacity of the cationic cellulose-based aerogel filter is 99.9% for MS2 and 93.6% for Qbeta, at pH = 7.0; and desorption of mostly intact viruses occurs at pH = 3.0. The results contribute to the fundamental understanding of pH-triggered virus-nanocellulose self-assembly and can guide the design of sustainable and environmentally friendly adsorption-based virus filter materials as well as phage and virus-based materials.

Nano-3D-Printed Photochromic Micro-Objects.

Molecular photoswitches that can reversibly change color upon irradiation are promising materials for applications in molecular actuation and photoresponsive materials. However, the fabrication of photochromic devices is limited to conventional approaches such as mold casting and spin-coating, which cannot fabricate complex structures. Reported here is the first photoresist for direct laser writing of photochromic 3D micro-objects via two-photon polymerization. The integration of photochromism into thiol-ene photo-clickable resins enables rapid two-photon laser processing of highly complex microstructures and facile postmodification using a series of donor-acceptor Stenhouse adduct (DASA) photoswitches with different excitation wavelengths. The versatility of thiol-ene photo-click reactions allows fine-tuning of the network structure and physical properties as well as the type and concentration of DASA. When exposed to visible light, these microstructures exhibit excellent photoresponsiveness and undergo reversible color-changing via photoisomerization. It is demonstrated that the fluorescence variations of DASAs can be used as a reporter of photoswitching and thermal recovery, allowing the reading of DASA-containing sub-micrometric structures in 3D. This work delivers a new approach for custom microfabrication of 3D photochromic objects with molecularly engineered color and responsiveness.

In vitro skin culture media influence the viability and inflammatory response of primary macrophages.

The replacement of animal models for investigation of inflammation and wound healing has been advancing by means of in vitro skin equivalents with increasing levels of complexity. However, the current in vitro skin models still have a limited pre-clinical relevance due to their lack of immune cells. So far, few steps have been made towards the incorporation of immune cells into in vitro skin and the requirements for immunocompetent co-cultures remain unexplored. To establish suitable conditions for incorporating macrophages into skin models, we evaluated the effects of different media on primary keratinocytes, fibroblasts and macrophages. Skin maturation was affected by culture in macrophage medium, while macrophages showed reduced viability, altered cell morphology and decreased response to pro- and anti-inflammatory stimuli in skin differentiation media, both in 2D and 3D. The results indicate that immunocompetent skin models have specific, complex requirements for supporting an accurate detection of immune responses, which point at the identification of a suitable culture medium as a crucial pre-requisite for the development of physiologically relevant models.

Influence of ceftriaxone on human bone cell viability and in vitro mineralization potential is concentration- and time-dependent.

AIMS: In orthopaedic and trauma surgery, implant-associated infections are increasingly treated with local application of antibiotics, which allows a high local drug concentration to be reached without eliciting systematic adverse effects. While ceftriaxone is a widely used antibiotic agent that has been shown to be effective against musculoskeletal infections, high local concentrations may harm the surrounding tissue. This study investigates the acute and subacute cytotoxicity of increasing ceftriaxone concentrations as well as their influence on the osteogenic differentiation of human bone progenitor cells. METHODS: Human preosteoblasts were cultured in presence of different concentrations of ceftriaxone for up to 28 days and potential cytotoxic effects, cell death, metabolic activity, cell proliferation, and osteogenic differentiation were studied. RESULTS: Ceftriaxone showed a cytotoxic effect on human bone progenitor cells at 24 h and 48 h at concentrations above 15,000 mg/l. With a longer incubation time of ten days, subtoxic effects could be observed at concentrations above 500 mg/l. Gene and protein expression of collagen, as well as mineralization levels of human bone progenitor cells, showed a continuous decrease with increasing ceftriaxone concentrations by days 14 and 28, respectively. Notably, mineralization was negatively affected already at concentrations above 250 mg/l. CONCLUSION: This study demonstrates a concentration-dependent influence of ceftriaxone on the viability and mineralization potential of primary human bone progenitor cells. While local application of ceftriaxone is highly established in orthopaedic and trauma surgery, a therapeutic threshold of 250 mg/l or lower should diminish the risk of reduced osseointegration of prosthetic implants. Cite this article: Bone Joint Res 2021;10(3):218-225.

Bioresponsive Hybrid Nanofibers Enable Controlled Drug Delivery through Glass Transition Switching at Physiological Temperature.

To avoid excessive usage of antibiotics and antimicrobial agents, smart wound dressings permitting controlled drug release for treatment of bacterial infections are highly desired. In search of a sensitive stimulus to activate drug release under physiological conditions, we found that the glass transition temperature (Tg) of a polymer or polymer blend can be an ideal parameter because a thermal stimulus can regulate drug release at the physiological temperature of 37 °C. A well-tuned Tg for a controlled drug release from fibers at 37 °C was achieved by varying the blending ratio of Eudragit® RS 100 and poly(methyl methacrylate). Octenidine, an antimicrobial agent often used in wound treatment, was encapsulated into the polymer blend during the electrospinning process and evaluated for its controlled release based on modulation of temperature. The thermal switch of the nanofibrous membranes can be turned "on" at physiological temperature (37 °C) and "off" at room temperature (25 °C), conferring a controlled release of octenidine. It was found that octenidine can be released in an amount at least 8.5 times higher (25 mg·L-1) during the "on" stage compared to the "off" stage after 24 h, which was regulated by the wet Tg (34.8-36.5 °C). The "on"/"off" switch for controlled drug release can moreover be repeated at least 5 times. Furthermore, the fabricated nanofibrous membranes displayed a distinctive antibacterial activity, causing a log3 reduction of the viable cells for both Gram negative and positive pathogens at 37 °C, when the thermal switch was "on". This study forms the groundwork for a treatment concept where no external stimulus is needed for the release of antimicrobials at physiological conditions, and will help reduce the overuse of antibiotics by allowing controlled drug release.

A microfluidic platform for in situ investigation of biofilm formation and its treatment under controlled conditions.

BACKGROUND: Studying bacterial adhesion and early biofilm development is crucial for understanding the physiology of sessile bacteria and forms the basis for the development of novel antimicrobial biomaterials. Microfluidics technologies can be applied in such studies since they permit dynamic real-time analysis and a more precise control of relevant parameters compared to traditional static and flow chamber assays. In this work, we aimed to establish a microfluidic platform that permits real-time observation of bacterial adhesion and biofilm formation under precisely controlled homogeneous laminar flow conditions. RESULTS: Using Escherichia coli as the model bacterial strain, a microfluidic platform was developed to overcome several limitations of conventional microfluidics such as the lack of spatial control over bacterial colonization and allow label-free observation of bacterial proliferation at single-cell resolution. This platform was applied to demonstrate the influence of culture media on bacterial colonization and the consequent eradication of sessile bacteria by antibiotic. As expected, the nutrient-poor medium (modified M9 minimal medium) was found to promote bacterial adhesion and to enable a higher adhesion rate compared to the nutrient-rich medium (tryptic soy broth rich medium ). However, in rich medium the adhered cells colonized the glass surface faster than those in poor medium under otherwise identical conditions. For the first time, this effect was demonstrated to be caused by a higher retention of newly generated bacteria in the rich medium, rather than faster growth especially during the initial adhesion phase. These results also indicate that higher adhesion rate does not necessarily lead to faster biofilm formation. Antibiotic treatment of sessile bacteria with colistin was further monitored by fluorescence microscopy at single-cell resolution, allowing in situ analysis of killing efficacy of antimicrobials. CONCLUSION: The platform established here represents a powerful and versatile tool for studying environmental effects such as medium composition on bacterial adhesion and biofilm formation. Our microfluidic setup shows great potential for the in vitro assessment of new antimicrobials and antifouling agents under flow conditions.

Water-Based Scalable Methods for Self-Cleaning Antibacterial ZnO-Nanostructured Surfaces.

Bacterial colonization poses significant health risks, such as infestation of surfaces in biomedical applications and clean water unavailability. If maintaining the surrounding water clean is a target, developing surfaces with strong bactericidal action, which is facilitated by bacterial access to the surface and mixing, can be a solution. On the other hand, if sustenance of a surface free of bacteria is the goal, developing surfaces with ultralow bacterial adhesion often suffices. Here we report a facile, scalable, and environmentally benign strategy that delivers customized surfaces for these challenges. For bactericidal action, nanostructures of inherently antibacterial ZnO, through simple immersion of zinc in hot water, are fabricated. The resulting nanostructured surface exhibits extreme bactericidal effectiveness (9250 cells cm-2 h-1) that eliminates bacteria in direct contact and also remotely through the action of reactive oxygen species. Remarkably, the remote bactericidal action is achieved without the need for any illumination, otherwise required in conventional approaches. As a result, ZnO nanostructures yield outstanding water disinfection of >99.98%, in the dark, by inactivating the bacteria within 3 h. Moreover, Zn2+ released to the aqueous medium from the nanostructured ZnO surface have a concentration of 0.73 ± 0.15 ppm, markedly below the legal limit for safe drinking water (5-6 ppm). The same nanostructures, when hydrophobized (through a water-based or fluorine-free spray process), exhibit strong bacterial repulsion, thus substantially reducing bacterial adhesion. Such environmentally benign and scalable methods showcase pathways toward inhibiting surface bacterial colonization.

Macromechanics and polycaprolactone fiber organization drive macrophage polarization and regulate inflammatory activation of tendon in vitro and in vivo.

Appropriate macrophage response to an implanted biomaterial is crucial for successful tissue healing outcomes. In this work we investigated how intrinsic topological cues from electrospun biomaterials and extrinsic mechanical loads cooperate to guide macrophage activation and macrophage-tendon fibroblast cross-talk. We performed a series of in vitro and in vivo experiments using aligned or randomly oriented polycaprolactone nanofiber substrates in both mechanically loaded and unloaded conditions. Across all experiments a disorganized biomaterial fiber topography was alone sufficient to promote a pro-inflammatory signature in macrophages, tendon fibroblasts, and tendon tissue. Extrinsic mechanical loading was found to strongly regulate the character of this signature by reducing pro-inflammatory markers both in vitro and in vivo. We observed that macrophages generally displayed a stronger response to biophysical cues than tendon fibroblasts, with dominant effects of cross-talk between these cell types observed in mechanical co-culture models. Collectively our data suggest that macrophages play a potentially important role as mechanosensory cells in tendon repair, and provide insight into how biological response might be therapeutically modulated by rational biomaterial designs that address the biomechanical niche of recruited cells.

Multifunctional Biomaterials: Combining Material Modification Strategies for Engineering of Cell-Contacting Surfaces.

In the human body, cells in a tissue are exposed to signals derived from their specific extracellular matrix (ECM), such as architectural structure, mechanical properties, and chemical composition (proteins, growth factors). Research on biomaterials in tissue engineering and regenerative medicine aims to recreate such stimuli using engineered materials to induce a specific response of cells at the interface. Although traditional biomaterials design has been mostly limited to varying individual signals, increasing interest has arisen on combining several features in recent years to improve the mimicry of extracellular matrix properties. Tremendous progress in combinatorial surface modification exploiting, for example, topographical features or variations in mechanics combined with biochemical cues has enabled the identification of their key regulatory characteristics on various cell fate decisions. Gradients especially facilitated such research by enabling the investigation of combined continuous changes of different signals. Despite unravelling important synergies for cellular responses, challenges arise in terms of fabrication and characterization of multifunctional engineered materials. This review summarizes recent work on combinatorial surface modifications that aim to control biological responses. Modification and characterization methods for enhanced control over multifunctional material properties are highlighted and discussed. Thereby, this review deepens the understanding and knowledge of biomimetic combinatorial material modification, their challenges but especially their potential.

Antibacterial, Cytocompatible, Sustainably Sourced: Cellulose Membranes with Bifunctional Peptides for Advanced Wound Dressings.

Progressive antibiotic resistance is a serious condition adding to the challenges associated with skin wound treatment, and antibacterial wound dressings with alternatives to antibiotics are urgently needed. Cellulose-based membranes are increasingly considered as wound dressings, necessitating further functionalization steps. A bifunctional peptide, combining an antimicrobial peptide (AMP) and a cellulose binding peptide (CBP), is designed. AMPs affect bacteria via multiple modes of action, thereby reducing the evolutionary pressure selecting for antibiotic resistance. The bifunctional peptide is successfully immobilized on cellulose membranes of bacterial origin or electrospun fibers of plant-derived cellulose, with tight control over peptide concentrations (0.2 ± 0.1 to 4.6 ± 1.6 µg mm-2 ). With this approach, new materials with antibacterial activity against Staphylococcus aureus (log4 reduction) and Pseudomonas aeruginosa (log1 reduction) are developed. Furthermore, membranes are cytocompatible in cultures of human fibroblasts. Additionally, a cell adhesive CBP-RGD peptide is designed and immobilized on membranes, inducing a 2.2-fold increased cell spreading compared to pristine cellulose. The versatile concept provides a toolbox for the functionalization of cellulose membranes of different origins and architectures with a broad choice in peptides. Functionalization in tris-buffered saline avoids further purification steps, allowing for translational research and multiple applications outside the field of wound dressings.

In Vitro Cytocompatibility Assessment of Ti-Modified, Silicon-oxycarbide-Based, Polymer-Derived, Ceramic-Implantable Electrodes under Pacing Conditions.

Polymer-derived ceramics (PDC) have recently gained increased interest in the field of bioceramics. Among PDC's, carbon-rich silicon oxycarbide ceramics (SiOC) possess good combined electrical and mechanical properties. Their durability in aggressive environments and proposed cytocompatibility makes them an attractive material for fabrication of bio-MEMS devices such as pacemaker electrodes. The aim of the present study is to demonstrate the remarkable mechanical and electrical properties, biological response of PDCs modified with titanium (Ti) and their potential for application as pacemaker electrodes. Therefore, a new type of SiOC modified with Ti fillers was synthesized via PDC route using a Pt-catalyzed hydrosilylation reaction. Preceramic green bodies were pyrolyzed at 1000 °C under an argon atmosphere to achieve amorphous ceramics. Electrical and mechanical characterization of SiCxO2(1-x)/TiOxCy ceramics revealed a maximum electrical conductivity of 10 S cm-1 and a flexural strength of maximal 1 GPa, which is acceptable for pacemaker applications. Ti incorporation is found to be beneficial for enhancing the electrical conductivity of SiOC ceramics and the conductivity values were increased with Ti doping and reached a maximum for the composition with 30 wt % Ti precursor. Cytocompatibility was demonstrated for the PDC SiOC ceramics as well as SiOC ceramics modified with Ti fillers. Cytocompatibility was also demonstrated for SiTiOC20 electrodes under pacing conditions by monitoring of cells in an in vitro 3D environment. Collectively, these data demonstrate the great potential of polymer-derived SiOC ceramics to be used as pacemaker electrodes.

Silk fibroin/sericin 3D sponges: The effect of sericin on structural and biological properties of fibroin.

Among naturally occurring polymers, silk fibroin and sericin have attracted much attention in the field of tissue engineering; however, clinical application of silk fibroin/sericin scaffolds in a combined form has been questioned due to the possible pro-inflammatory reaction against native silk and fibroin/sericin 3D constructs. The objective of this study was to fabricate 3D spongy fibroin/sericin scaffolds and to explore the structural, biological and immunological properties of different ratios of fibroin and sericin. Structural characterization revealed a highly porous structure (>91%) with a large surface area and water uptake capacity for all different fibroin/sericin scaffolds. Notably, the scaffolds showed enhanced mechanical properties and a higher degradation rate with increasing sericin content. Excellent cell attachment and no significant cytotoxicity were observed in all scaffold types 7 days after seeding of osteoblast-like MG63 cells. Gene expression of pro-inflammatory markers TNF-α, CXCL10 and CD197 as well as TNF-α secretion by THP-1-derived macrophages revealed no significant immune response to all fibroin/sericin scaffold types when compared to sericin-free F1:S0 samples and a TCP (Mɸ) control group. These results demonstrate that spongy fibroin/sericin scaffolds are able to support the growth of osteoblast-like cells without eliciting a pro-inflammatory response, thus being a promising material for bone tissue engineering.

Nylon-6/chitosan core/shell antimicrobial nanofibers for the prevention of mesh-associated surgical site infection.

The state-of-the-art hernia meshes, used in hospitals for hernia repair, are predominantly polymeric textile-based constructs that present high mechanical strength, but lack antimicrobial properties. Consequently, preventing bacterial colonization of implanted prosthetic meshes is of major clinical relevance for patients undergoing hernia repair. In this study, the co-axial electrospinning technique was investigated for the development of a novel mechanically stable structure incorporating dual drug release antimicrobial action. Core/shell structured nanofibers were developed, consisting of Nylon-6 in the core, to provide the appropriate mechanical stability, and Chitosan/Polyethylene oxide in the shell to provide bacteriostatic action. The core/shell structure consisted of a binary antimicrobial system incorporating 5-chloro-8-quinolinol in the chitosan shell, with the sustained release of Poly(hexanide) from the Nylon-6 core of the fibers. Homogeneous nanofibers with a "beads-in-fiber" architecture were observed by TEM, and validated by FTIR and XPS. The composite nanofibrous meshes significantly advance the stress-strain responses in comparison to the counterpart single-polymer electrospun meshes. The antimicrobial effectiveness was evaluated in vitro against two of the most commonly occurring pathogenic bacteria; S. aureus and P. aeruginosa, in surgical site infections. This study illustrates how the tailoring of core/shell nanofibers can be of interest for the development of active antimicrobial surfaces.