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Due to organ donor shortages, long transplant waitlists, and the complications/limitations associated with auto and allotransplantation, biomaterials and tissue-engineered models are gaining attention as feasible alternatives for replacing and reconstructing damaged organs and tissues. Among various tissue engineering applications, bone tissue engineering has become a promising strategy to replace or repair damaged bone. We aimed to provide an overview of bioactive ceramic scaffolds in bone tissue engineering, focusing on angiogenesis and the effect of different biofunctionalization strategies. Different routes to angiogenesis, including chemical induction through signaling molecules immobilized covalently or non-covalently, in situ secretion of angiogenic growth factors, and the degradation of inorganic scaffolds, are described. Physical induction mechanisms are also discussed, followed by a review of methods for fabricating bioactive ceramic scaffolds via microfabrication methods, such as photolithography and 3D printing. Finally, the strengths and weaknesses of the commonly used methodologies and future directions are discussed., QC 20240321

As physical topographical features suggest important effects in bone tissue engineering, an increasing amount of research on surface topographies has been carried out. In this work, melt electrowritten PCL scaffolds (mPCL) with recrystallized surfaces for osteogenic differentiation were constructed. The recrystallized grid PCL scaffolds (rPCL) show strengthened mechanical properties, retained biocompatibility, enhanced expression of alkaline phosphatase, and improved calcium mineralization compared to uncrystallized mPCL scaffolds, thereby confirming the promotion of osteogenic differentiation. In addition, lumbar vertebra-like rPCL scaffolds were successfully printed for precursor osteoblast-like cells to cellularize in the desired pattern. Importantly, the combination of recrystallization method and MEW technology introduced new function into the MEW based tissue engineering scaffolds, presenting the nano/microstructure of PCL on macroscale PCL scaffolds with enhanced osteogenic activities, which especially opens a new facile route for MEW scaffolds to broaden their applications in bone tissue engineering., QC 20240318

Spider silk—an environmentally friendly protein-based material—is widely recognized for its extraordinary mechanical properties. Biomimetic spider silk-like fibers made from recombinant spider silk proteins (spidroins) currently falls short compared to natural silks in terms of mechanical performance. In this study, it is discovered that spiders use structural conversion of molecular enhancers—conserved globular 127-residue spacer domains—to make strong silk fibers. This domain lacks poly-Ala motifs but interestingly contains motifs that are similar to human amyloidogenic motifs, and that it self-assembles into amyloid-like fibrils through a non-nucleation-dependent pathway, likely to avoid the formation of cytotoxic intermediates. Incorporating this spacer domain into a recombinant chimeric spidroin facilitates self-assembly into silk-like fibers, increases fiber molecular homogeneity, and markedly enhances fiber mechanical strength. These findings highlight that spiders employ diverse strategies to produce silk with exceptional mechanical properties. The spacer domain offers a way to enhance the properties of recombinant spider silk-like fibers and other functional materials.

Efficient, simple antibacterial materials to combat implant-associated infections are much in demand. Herein, the development of polyurethanes, both cross-linked thermoset and flexible and versatile thermoplastic, suitable for “click on demand” attachment of antibacterial compounds enabled via incorporation of an alkyne-containing diol monomer in the polymer backbone, is described. By employing different polyolic polytetrahydrofurans, isocyanates, and chain extenders, a robust and flexible material comparable to commercial thermoplastic polyurethane is prepared. A series of short synthetic antimicrobial peptides are designed, synthesized, and covalently attached in a single coupling step to generate a homogenous coating. The lead material is shown to be biocompatible and does not display any toxicity against either mouse fibroblasts or reconstructed human epidermis according to ISO and OECD guidelines. The repelling performance of the peptide-coated materials is illustrated against colonization and biofilm formation by Staphylococcus aureus and Staphylococcus epidermidis on coated plastic films and finally, on coated commercial central venous catheters employing LIVE/DEAD staining, confocal laser scanning microscopy, and bacterial counts. This study presents the successful development of a versatile and scalable polyurethane with the potential for use in the medical field to reduce the impact of bacterial biofilms., This study was financed by Amicoat A/S. The authors are grateful for the analytical assistance from RISE scientists L. Brive, P. Borchardt, K. Johansson, and J. Somertune.

Ionic liquids (ILs) are a class of salts existing in the liquid state below 100 degrees C, possessing low volatility, high thermal stability as well as many highly attractive solvent and electrochemical capabilities, etc., making them highly tunable for a great variety of applications, such as lubricants, electrolytes, and soft functional materials. In many applications, ILs are first either physi- or chemisorbed on a solid surface to successively create more functional materials. The functions of ILs at solid surfaces can differ considerably from those of bulk ILs, mainly due to distinct interfacial layers with tunable structures resulting in new ionic liquid interface layer properties and enhanced performance. Due to an almost infinite number of possible combinations among the cations and anions to form ILs, the diversity of various solid surfaces, as well as different external conditions and stimuli, a detailed molecular-level understanding of their structure-property relationship is of utmost significance for a judicious design of IL-solid interfaces with appropriate properties for task-specific applications. Many experimental techniques, such as atomic force microscopy, surface force apparatus, and so on, have been used for studying the ion structuring of the IL interface layer. Molecular Dynamics simulations have been widely used to investigate the microscopic behavior of the IL interface layer. To interpret and clarify the IL structure and dynamics as well as to predict their properties, it is always beneficial to combine both experiments and simulations as close as possible. In another theoretical model development to bridge the structure and properties of the IL interface layer with performance, thermodynamic prediction & property modeling has been demonstrated as an effective tool to add the properties and function of the studied nanomaterials. Herein, we present recent findings from applying the multiscale triangle experiment-simulation-thermodynamic

This thesis presents a comprehensive study on stimuli-responsive materials derived from cellulose nanofibrils (CNFs), focusing on their synthesis, characterization, and performance evaluation in various applications. Renowned for their biodegradability, renewability, and robust mechanical properties, CNFs are explored in three primary contexts: moisture-responsive actuators, voltage-responsive actuators, and CO2-responsive sensors. The unique properties of CNFs, such as high tensile strength and surface area, are leveraged to achieve effective motion in response to moisture exposure. Specifically, CNFs are utilized to create bilayer, torsional, and tensile actuators. These actuators exhibit controllable and dynamic responses, making them suitable for applications in soft robotics and wearable technology. In the realm of voltage-responsive actuators, this study investigates the impact of various electrolytes and counteranions on positively charged CNFs. It uncovers the critical role of electrolyte choice, ion migration and the plasticization effect within the CNFs matrix, resulting in volumetric expansion, which is pivotal to the actuation mechanism. These insights pave the way for CNFs applications requiring precise control of motion and flexibility in shape, such as in soft robotics. The third area of application involves the development of a capacitive CO2 sensor using CNFs-based foams functionalized with primary amines to enhance CO2 capture through chemisorption. This functionalization turns the CNFs-based foam into an efficient dielectric layer (DE) for sensor applications. The addition of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to the DE further expands the scope of sensor's capacitance change in response to CO2 exposure, underscoring its potential in environmental monitoring and CO2 detection. Overall, this thesis emphasizes the versatility and adaptability of CNFs as a sustainable biomaterial for developing stimuli-responsive devices. The insights gained fr

As a biodegradable and biocompatible protein derived from collagen, gelatin has been extensively exploited as a fundamental component of biological scaffolds and drug delivery systems for precise medicine. The easily engineered gelatin holds great promise in formulating various delivery systems to protect and enhance the efficacy of drugs for improving the safety and effectiveness of numerous pharmaceuticals. The remarkable biocompatibility and adjustable mechanical properties of gelatin permit the construction of active 3D scaffolds to accelerate the regeneration of injured tissues and organs. In this Review, we delve into diverse strategies for fabricating and functionalizing gelatin-based structures, which are applicable to gene and drug delivery as well as tissue engineering. We emphasized the advantages of various gelatin derivatives, including methacryloyl gelatin, polyethylene glycol-modified gelatin, thiolated gelatin, and alendronate-modified gelatin. These derivatives exhibit excellent physicochemical and biological properties, allowing the fabrication of tailor-made structures for biomedical applications. Additionally, we explored the latest developments in the modulation of their physicochemical properties by combining additive materials and manufacturing platforms, outlining the design of multifunctional gelatin-based micro-, nano-, and macrostructures. While discussing the current limitations, we also addressed the challenges that need to be overcome for clinical translation, including high manufacturing costs, limited application scenarios, and potential immunogenicity. This Review provides insight into how the structural and chemical engineering of gelatin can be leveraged to pave the way for significant advancements in biomedical applications and the improvement of patient outcomes.

Cadmium telluride (CdTe) semiconductor quantum dots (QDs) are brightly luminescent nanocrystals that have emerged as a new class of fluorescent probes for in vivo bioimaging and theranostic applications. CdTe QDs toxicity to normal human cells is minimized by coating with a less toxic ZnS and ZnSe shell forming a core–shell nanostructure. However, coating with ZnS or ZnSe shell is insufficient to prevent the leaching of toxic Cd metal ions. To further minimize toxicity, thiol dual capped CdTe/CdSe/ZnSe multi-core-multi-shell quantum dots were coated with nanoliposome or liposome vesicles (CdTe/CdSe/ZnSe@liposome) and chitosan nanoparticles (CdTe/CdSe/ZnSe@ChitNPs) and their biocompatibility on HeLa and Vero cells were investigated. Different spectroscopic and microscopic techniques were used to elucidate nanocomposites' optical, morphological, and physicochemical properties. The coating of CdTe/CdSe/ZnSe multi-core-multi-shell quantum dots were conducted at different formulations (F1, F2 and F3) and results from the fluorescence studies show that F3 demonstrated the best interaction for both liposome and ChitNPs composite. Exposure to 12 h UV illumination studies also reveals that CdTe/CdSe/ZnSe@liposome shows an enhancement in fluorescence compared to CdTe/CdSe/ZnSe@ChitNPs. The cytotoxicity of the formulations towards HeLa and Vero cells also depicted minimal toxicity compared to CdTe/CdSe/ZnSe QDs that shows much higher toxicity (IC50 = 0.09381 mg/ml). It was further observed that liposome coated multi-core-multi-shell QDs@F2 demonstrated lower toxicity (IC50 = 0.4364 mg/ml) compared to ChitNPs coated multi-core-multi-shell QDs@F2 (IC50 = 0.1618 mg/ml). Results from the florescence imaging studies reveal that CdTe/CdSe/ZnSe-multi-core-multi-shell QDs liposomes and ChitNPs composite retained most of their fluorescence and properties and could easily be tracked in cells and visualized around the nucleus. This indicates the successful internalization of the QDs in t

Back pain, affecting 80% of the population, significantly strains the healthcare system. In European countries, spine-related hospital discharges account for 14.2% to 45.6% of all musculoskeletal disease discharges. Conservative treatments like medication and physical therapy are generally preferred, but surgical intervention may be necessary for some. Spinal surgeries often involve implants, such as spinal cages, spinal instrumentation, or total disc replacements, used to treat abnormal spinal curvatures or intervertebral disc degeneration. Despite their widespread use, spinal implants face challenges such as failed vertebral fusion, infections, and implant failure, which can release harmful ions and particles. Researchers are developing new materials with antibacterial properties and improved interaction with bone tissue. Innovations include wear-resistant coatings to prevent metal ion release and biodegradable materials that the body gradually replaces, reducing infection risks and the need for revision surgeries. However, these advances present challenges. Degradation by-products can migrate more easily to other parts of the body and may elicit unwanted biological responses. The primary aim of this thesis was to investigate the biological effects of these degradation products from an in vitro perspective. This involved using several relevant cell types and examining morphological and functional changes. A composite of calcium phosphate and polylactic acid was initially examined for spinal fusion. The cell response to the degradation products was comparable to those of a clinically successful calcium phosphate, showing no negative impact on preosteoblast cells. Additionally, silicon nitride (SiN) coatings, known for their wear resistance properties, were explored. The incorporation of additional elements into SiN coatings was studied to enhance stability and durability. It was found that fibroblast and microglial cells tolerated the ions and particles released du

Polyphenol is a versatile green phytochemical vital in several biomedical applications with fascinating inherent biocompatible, bioadhesive, antioxidant, and antibacterial properties. The emergence of novel nanotechnology techniques, such as electrospinning, has proven to be an excellent option for applications in nanotechnology, ensuring an effective drug delivery system for recognised medicinal plant extracts containing polyphenols as electrospun nanofibers can provide the necessary environment for encapsulation. Together, electrospun nanofibers and polyphenols have shown promising usage in wound healing. When polyphenols are incorporated into nanofibrous scaffolds, their combined properties enhance cell attachment, proliferation, and differentiation. This review explores the potential of polyphenol-loaded nanofibers for wound therapy, highlighting the importance of efficient drug delivery systems for electrospun polyphenols. It provides a brief assessment of specific polyphenols (resveratrol, curcumin, thymol, quercetin, tannic acid, ferulic acid, hesperidin, gallic acid, kaempferol, chlorogenic acid) that have been successfully encapsulated in electrospun nanofibers and applied in wound treatment. Despite ongoing research, certain polyphenols such as carvacrol, oleuropein, chlorogenic acid, gallic acid, and kaempferol in electrospun nanofibers remain less explored. This review underscores the need for continued investigation into these promising systems while recognising the growing application of polyphenol-loaded nanofibers in wound healing and their potential for more extensive therapeutic use.

Silicon nitride is utilized clinically as a bioceramic for spinal fusion cages, owing to its high strength, osteoconductivity, and antibacterial effects. Nevertheless, silicon nitride exhibits suboptimal damping properties, a critical factor in mitigating traumatic bone injuries and fractures. In fact, there is a scarcity of spinal implants that simultaneously demonstrate proficient damping performance and support osteogenesis. In our study, we fabricated a novel sodium alginate-silicon nitride/poly(vinyl alcohol) (SA-SiN/PVA) composite scaffold, enabling enhanced energy absorption and rapid elastic recovery under quasi-static and impact loading scenarios. Furthermore, the study demonstrated that the incorporation of physical and chemical cross-linking significantly improved stiffness and recoverable energy dissipation. Concerning the interaction between cells and materials, our findings suggest that the addition of silicon nitride stimulated osteogenic differentiation while inhibiting Staphylococcus aureus growth. Collectively, the amalgamation of ceramics and tough hydrogels facilitates the development of advanced composites for spinal implants, manifesting superior damping, osteogenic potential, and antibacterial properties. This approach holds broader implications for applications in bone tissue engineering.

Thrombotic cardiovascular diseases are a prevalent factor contributing to both physical impairment and mortality. Thrombolysis and ischemic mitigation have emerged as leading contemporary therapeutic approaches for addressing the consequences of ischemic injury and reperfusion damage. Herein, an innovative cellular-cloaked spermatozoon-driven microcellular submarine (SPCS), comprised of multimodal motifs, was designed to integrate nano-assembly thrombolytics with an immunomodulatory ability derived from innate magnetic hyperthermia. Rheotaxis-based navigation was utilized to home to and cross the clot barrier, and finally accumulate in ischemic vascular organs, where the thrombolytic motif was “switched-on” by the action of thrombus magnetic red blood cell-driven magnetic hyperthermia. In a murine model, the SPCS system combining innate magnetic hyperthermia demonstrated the capacity to augment delivery efficacy, produce nanotherapeutic outcomes, exhibit potent thrombolytic activity, and ameliorate ischemic tissue damage. These findings underscore the multifaceted potential of our designed approach, offering both thrombolytic and ischemia-mitigating effects. Given its extended therapeutic effects and thrombus-targeting capability, this biocompatible SPCS system holds promise as an innovative therapeutic agent for enhancing efficacy and preventing risks after managing thrombosis., QC 20240813

The field of medicine has traditionally relied solely on small molecular drugs and conventional surgical procedures. However, recent advancements have shifted the focus toward innovative approaches, such as tissue engineering and regenerative medicine, which aim to overcome the limitations of traditional treatments through personalized and precision medicine. This thesis investigates tissue repair strategies using minimally invasive methods, specifically through the application of injectable biomaterials with or without cell-derived therapeutic factors. To this end, a series of novel injectable hydrogels were developed, alongside protocols for the reliable isolation of extracellular vesicles. These components were then integrated to create injectable therapeutic hydrogels. In Paper I, an injectable collagen-based hydrogel was developed. The injectable hydrogel maintained its shape in aqueous buffers, was biodegradable by the body's own enzymes, and supported the encapsulation and attachment of model cells. In Paper II, the collagen hydrogel from Paper I was further developed for use as a corneal sealant in corneal perforations. The hydrogel retained its beneficial properties of being shape-holding, biodegradable, and supporting cell attachment. Additionally, it exhibited increased transparency and tunable mechanical properties through minor adjustments in stoichiometry. It also successfully withstood burst pressures exceeding normal intraocular pressure levels and demonstrated adhesive properties comparable to fibrin glue, while supporting corneal epithelialization. Altogether, showing promise as an injectable corneal sealant. In Paper III, extracellular vesicles from corneal epithelial cells were isolated, purified and characterized based on their size, morphology, surface protein pattern and protein content. Corneal epithelial extracellular vesicles are thought to promote wound healing which could be confirmed with a functional in vitro scratch assay. These therap

The culture of cells in 3D creates a more physiologically relevant cell environment than conventional 2D cultures. Interactions of cells with the extracellular matrix induce important cellular signalling that regulates cell adhesion, migration, proliferation, differentiation, and survival. This is crucial for modelling cell development and disease. This thesis aims to develop and analyse improved 3D cell culture methods for stem cell-derived pancreatic islets (SC-islets) and breast cancer cell lines using a functionalized recombinant spider silk. Spider silk is a natural protein-based material with remarkable mechanical properties of high strength and elasticity. It is also biodegradable and cytocompatible. FN-silk, the recombinant spider silk protein utilized in this thesis, is functionalized with a cell binding motif (RGD) from fibronectin, to improve cell adhesion. Notably, FN-silk self-assembles at the liquid-air interface into a fibrillar structure, making it favourable as support for cell culture. In this thesis, bioinformatic methods were used to discover how the FN-silk supported environment affects the gene expression of cells and the cellular heterogeneity of SC-islets during a differentiation process. Additionally, bioinformatical analysis of the effect of 3D cell culture of breast cancer cell lines in FN-silk networks was performed. The first part of the thesis addresses serval challenges in pancreatic islet transplantation, by presenting an optimized protocol for pancreatic differentiation from human pluripotent stem cells, improving in vitro cultivation, and developing a cryopreservation method for SC-islets. The differentiation protocol presented in Paper 1 resulted in pure endocrine cell populations, avoiding unwanted proliferating and non-endocrine cells. It was also demonstrated that these SC-islets matured in vivo, and could effectively reverse diabetes in a diabetic mouse model. Single-cell RNA sequencing analysis provided new insights into the c, Odling av celler i 3D skapar en mer fysiologiskt relevant cellmiljö än konventionella 2D-kulturer. Interaktioner mellan celler och den extracellulära matrisen inducerar viktiga cellsignaler som reglerar celladhesion, migration, proliferation, differentiering och överlevnad. Denna avhandling syftar till att utveckla och analysera förbättrade 3D-cellodlingsmetoder för stamcellsderiverade pankreatiska öar (SC-islets) och bröstcancerceller, med hjälp av funktionaliserat rekombinant spindelsilke. Spindelsilke är ett naturligt proteinbaserat material med anmärkningsvärda mekaniska egenskaper som hög styrka och elasticitet. Det är också biologiskt nedbrytbart och cellkompatibelt. FN-silk, det rekombinanta spindelsilkesprotein som används i denna avhandling, är funktionaliserat med ett cellbindande motiv (RGD) från fibronektin, för att förbättra celladhesion. Anmärkningsvärt är att det går samman vid vätska-luft-gränsytan till en fibrillär struktur, vilket gör det gynnsamt som stöd för cellodling. I denna avhandling användes bioinformatiska metoder för att studera hur 3D-miljön påverkar cellernas genuttryck och den cellulära heterogeniteten i pankreatiska aggregat under en differentieringsprocess. Dessutom utfördes en bioinformatisk analys av effekten av 3D-cellodling av bröstcancercellinjer i FN-silknätverk. Den första delen av avhandlingen tar upp flera utmaningar vid transplantation av pankreatiska öar genom att presentera ett optimerat protokoll för pankreasdifferentiering från humana pluripotenta stamceller, förbättra in vitro-odling av dessa, samt utveckla en kryokonserveringsmetod för SC-islets. Differentieringsprotokollet som presenteras i Paper 1 resulterade i rena endokrina cellpopulationer och undviker oönskade prolifererande och icke-endokrina celler. Det visades också att dessa SC-islets mognade in vivo och kunde effektivt motverka diabetes i en diabetisk musmodell. Singel cell-RNA-sekvenseringsanalys gav nya insikter om den cellulära sammansättningen och genut, QC 2024-08-30

Since the 1960s, biosensors have been used in various fields of society including medicine. Many biomarkers are in low concentrations in bodily fluids, hence, the development of sensitive biosensors is necessary. Biosensors used in medicine can utilise various physical phenomena e.g. optical, electrochemical, and electrokinetics. In this study, the project will assess the use of electrokinetic phenomena streaming current to detect single-stranded DNA (ssDNA). In the study, a microchip streaming current analyzer with parallel microfluidic channels was utilized to detect single-stranded DNA. The walls of the microchannels were coated with peptide nucleic acid (PNA) as a capture probe for the detection. Additionally, the experimental setup and electrical parameters were analyzed. The project results showed a deviation of the flow rate between the theory and experimental result caused by the inwards bending of polydimethylsiloxane (PDMS). Platinum electrodes worked according to theory and the system operated leakfree. Detection of target DNA was successful and selectivity of the system was proven. The microfluidic biosensor showed positive results that are significant for clinical application, particularly in the non-invasive detection of biomarkers through liquid biopsy. The high sensitivity, precision, and dependability of the biosensor are an indication of a valuable instrument opening doors to numerous biomedical settings such as early cancer detection and monitoring.

Our aim was to investigate axonal outgrowth from different tissue models on soft biomaterials based on hyaluronic acid (HA). We hypothesized that HA-based hydrogels differentially promote axonal outgrowth from different neural tissues. Spinal cord sliced cultures (SCSCs) and dorsal root ganglion cultures (DRGCs) were maintained on a collagen gel, a physically crosslinked HA-based hydrogel (Healon 5®) and a novel chemically crosslinked HA-based hydrogel, with or without the presence of neurotrophic factors (NF). Time-lapse microscopy was performed after two, five and eight days, where axonal outgrowth was assessed by automated image analysis. Neuroprotection was investigated by PCR. Outgrowth was observed in all groups; however, in the collagen group, it was scarce. At the middle timepoint, outgrowth from SCSCs was superior in both HA-based groups compared to collagen, regardless of the presence of NF. In DRGCs, the outgrowth in Healon 5® with NF was significantly higher compared to the rest of the groups. PCR revealed upregulation of NeuN gene expression in the HA-based groups compared to controls after excitotoxic injury. The differences in neurite outgrowth from the two different tissue models suggest that axons differentially respond to the two types of biomaterials.

Transnational companies have substantive impacts on nature: a hallmark of living in the Anthropocene. Understanding these impacts through company provision of information is a precursor to holding them accountable for nature outcomes. The effect of increasing disclosures (of varying quality) is predicated on 'information governance', an approach that uses disclosure requirements to drive company behaviour. However, its efficacy is not guaranteed. We argue that three conditions are required before disclosures have the possibility to shape nature outcomes, namely: (1) radical traceability that links company actions to outcomes in particular settings; (2) developing organizational routines, tools and approaches that translate strategic intent to on-the-ground behaviour; and (3) mobilizing and aligning financial actors with corporate nature ambitions. While disclosure is key to each of these conditions, its limits must be taken into account and it must be nested in governance approaches that shape action, not just reporting.This article is part of the theme issue 'Bringing nature into decision-making'.

Amorphous iron-calcium phosphate (Fe-ACP) plays a vital role in the mechanical properties of teeth of some rodents, which are very hard, but its formation process and synthetic route remain unknown. Here, the synthesis and characterization of an iron-bearing amorphous calcium phosphate in the presence of ammonium iron citrate (AIC) are reported. The iron is distributed homogeneously on the nanometer scale in the resulting particles. The prepared Fe-ACP particles can be highly stable in aqueous media, including water, simulated body fluid, and acetate buffer solution (pH 4). In vitro study demonstrates that these particles have good biocompatibility and osteogenic properties. Subsequently, Spark Plasma Sintering (SPS) is utilized to consolidate the initial Fe-ACP powders. The results show that the hardness of the ceramics increases with the increase of iron content, but an excess of iron leads to a rapid decline in hardness. Calcium iron phosphate ceramics with a hardness of 4 GPa can be achieved, which is higher than that of human enamel. Furthermore, the ceramics composed of iron-calcium phosphates show enhanced acid resistance. This study provides a novel route to prepare Fe-ACP, and presents the potential role of Fe-ACP in biomineralization and as starting material to fabricate acid-resistant high-performance bioceramics.

Construction of organic-inorganic composites similar to natural bone in terms of structure and composition has attracted extensive attention. However, the clinical applications of these composites are limited due to the insufficient osteogenic and mechanical properties. In nature, the presence of amorphous iron-calcium phosphate (Fe-ACP) strengthens the mechanical properties of some biominerals, and our previous study has revealed its synthetic route and in vitro osteogenic properties. However, the potential role of Fe-ACP on biomineralization and constructing biomimetic scaffolds for bone regeneration has not been studied. Herein, a biomimetic scaffold with good osteogenic property was fabricated based on the mineralization of Fe-ACP, with the assistance of ice-templated freeze-casting. The in vitro study showed that the mineralized scaffolds possessed favorable biocompatibility and osteogenic property. Moreover, the scaffolds promoted cell chemotaxis and angiogenic property by upregulating the hypoxia inducible factor-1 alpha (HIF-1 alpha). In vivo experiment demonstrated potent early osteogenesis along with angiogenesis and ultimately promoted bone regeneration. Overall, the mineralized scaffold mediated by Fe-ACP precursors provide a unique platform to enhance bone tissue repair.

The overarching objective of this thesis was to develop intervertebral implants for degenerated discs through design, fabrication, and mechanical validation. The research had four primary aims, each addressing different facets of implant development. The first aim was to design a structurally optimized fusion intervertebral cage capable of accommodating weak bioactive materials. Topology optimization was employed to design cages using titanium and calcium phosphate. The cage’s integrity was verified using finite element simulations, fabricated using additive manufacturing, and validated using ASTM F2077. Imaging techniques were utilized to assess the quality of the produced cages. These evaluations confirmed the mechanical reliability of the produced cage, able to incorporate around 75% in volume of a bioactive calcium phosphate material, protected by the titanium. The second aim was to develop a clinically relevant degeneration model for the biomechanical evaluation of percutaneous cement discoplasty (PCD). To this end, voids were generated in ovine functional spinal units (FSUs) using papain. The results were compared with clinical data where parameters such as void volume percentage, disc height, and morphology of the induced injury were assessed. FSUs were treated with PCD using bone cement, and mechanically evaluated under healthy, injured, and treated conditions to determine if PCD could stabilize the spinal segment. The void induced showed similar parameters compared to the clinical data. Further, the stability of the spine was significantly reduced after degeneration and restored after treatment, highlighting the effectiveness of the degeneration method and PCD treatment. The third aim was to evaluate the suitability of novel bone cements for their use in PCD. This study examined the tensile and fatigue properties of a low-modulus cement (VSLA) primarily intended for vertebroplasty. The formulation was tested in tensile and fatigue. VSLA showed a significant

Background: Polymethylmethacrylate (PMMA) bone cement is extensively used in spinal procedures such as vertebroplasty and kyphoplasty, while its use in percutaneous cement discoplasty (PCD) is not yet widely spread. A main issue for both application sites, vertebra and disc, is the mismatch in stiffness between cement and bone, potentially resulting in adjacent vertebral fractures and adjacent segment disease. Tailoring the cement modulus using additives is hence an interesting strategy. However, there is a lack of data on the tensile and tension-compression fatigue properties of these cements, relevant to the newly researched indication of PCD. Method: A commercial PMMA cement (VS) was modified with 12%vol of linoleic acid (VSLA) and tested for quasi-static tensile properties. Additionally, tension-compression fatigue testing with amplitudes ranging from +/-5MPa to +/-7MPa and +/-9MPa was performed, and a Weibull three-parameter curve fit was used to calculate the fatigue parameters. Results: Quasi-static testing revealed a significant reduction in VSLA’s Young’s Modulus (E=581.1±126.4MPa) compared to the original cement (E=1478.1±202.9MPa). Similarly, the ultimate tensile stress decreased from 36.6±1.5MPa to 11.6±0.8MPa. Thus, VSLA offers improved compatibility with trabecular bone properties. Fatigue testing of VSLA revealed that as the stress amplitude increased the Weibull mean number decreased from 3591 to 272 and 91 cycles, respectively. In contrast, the base VS cement reached run-out at the highest stress amplitude. However, the lowest stress amplitude used exceeds the pressures recorded in the disc in vivo, and VSLA displayed a similar fatigue life range to that of the annulus fibrosis tissue. Conclusions: While the relevance of fully reversed tension-compression fatigue testing can be debated for predicting cement performance in certain spinal applications, the results of this study can serve as a benchmark for comparison of low-modulus cements for the s

Hydrogels of cellulose nanofibrils (CNFs) are promising wound dressing candidates due to their biocompatibility, high water absorption, and transparency. Herein, two different commercially available wood species, softwood and hardwood, were subjected to TEMPO-mediated oxidation to proceed with delignification and oxidation in a one-pot process, and thereafter, nanofibrils were isolated using a high-pressure microfluidizer. Furthermore, transparent nanofibril hydrogel networks were prepared by vacuum filtration. Nanofibril properties and network performance correlated with oxidation were investigated and compared with commercially available TEMPO-oxidized pulp nanofibrils and their networks. Softwood nanofibril hydrogel networks exhibited the best mechanical properties, and in vitro toxicological risk assessment showed no detrimental effect for any of the studied hydrogels on human fibroblast or keratinocyte cells. This study demonstrates a straightforward processing route for direct oxidation of different wood species to obtain nanofibril hydrogels for potential use as wound dressings, with softwood having the most potential., Validerad;2024;Nivå 2;2024-03-27 (hanlid);Full text license: CC BY 4.0, HEALiX

Cancer represents a significant global public health challenge and ranks as the second mostcommon cause of death in the United States. The onset of cancer entails an initial phasewhere cells lose their polarity and disconnect from the normal basement membrane, allowingthem to form distinct three-dimensional (3D) configurations that interact with adjacent cellsand the surrounding microenvironment. Cells grown in 2D monolayers demonstrate differentgene expression patterns and different activation of signaling pathways compared to cellscultivated within the natural structure of tumor tissue of the same cell type. Multicellulartumor spheroids (MCTS) are extensively investigated as a well-studied model of organotypiccancer. These spheroids are formed by tumor cells, either alone or in combination with othercell types, and they can be created with or without the application of supportive scaffolds.The MCTSs are also considered promising models for preclinical assessments of chemosensitivity.However, the creation of these tumor spheroids presents challenges, as not alltumor cell lines can consistently form regular spheroids.Cellulose nanofibrils (CNF) have become essential as a sustainable and environmentallyfriendly material. For example, thin films, with inherent mechanical properties, and flexibility,offer versatility across various applications. Also known for its biocompatibility and non-toxicnature, native CNF is a natural option to use. Its fibrous structure closely mimics the collagenmatrix in human tissue, showing potential as an effective scaffold for 3D cell culture. In thisregard, an innovative Layer-by-Layer (LbL) coating technique using CNF-polyelectrolytebilayers was investigated to generate spheroids. This method constructs bilayers of CNFand polyelectrolytes and can coat various surfaces. In this thesis, the first focus was ondemonstrating the spheroid formation capability using low molecular weight polyelectrolytesin LbL assembly. Secondly, an investigati, Cancer utgör en betydande global utmaning inom folkhälsan och rankas som den nästvanligaste dödsorsaken i USA. Cancer börjar med en initial fas där celler förlorar sin polaritetoch lossnar från basalmembranet, vilket tillåter dem att bilda distinkta tredimensionella (3D)kluster som interagerar med intilliggande celler och den omgivande mikromiljön. Celler somodlas i 2D-monolager visar olika genuttryck och olika signalvägar jämfört med celler somodlas som mer naturlig 3D struktur likt tumörvävnad. Multicellulära tumörsfärer (MCTS) ärväl studerade som modell för organotypisk cancer, dessa sfärer bildas av tumörceller,antingen av samma typ eller i kombination med andra celltyper, och de kan skapas medeller utan användning av underliggande stödjande strukturer. MCTS betraktas även somlovande modell för preklinisk bedömning av cellernas kemokänslighet. Dock är skapandetav dessa tumörsfärer utmanande, eftersom alla tumörcellinjer inte verkar kunna bildaregelbundna sfärer.Cellulosananofibriller (CNF) är ett alternativ som hållbart och miljövänligt material. Sombland annat kan forma till tunna filmer, med inbyggda mekaniska egenskaper, flexibilitet ,erbjuder mångsidighet över olika tillämpningsområden, till följd av dess flexibilitet och dessinbyggda mekaniska egenskaper. Känd för sin biokompatibilitet och ofarliga natur fungerarCNF som ett bra alternativ för användning även inom biomedicinska tillämpningar. CNFstrukturen liknar kollagenmatrisen i mänsklig vävnad och visar potential som ett effektivtunderlag för 3D-cellodling. Inom detta område undersöktes en innovativ lager-på-lager (LbL)beläggningsmetod innehållande CNF och polyelektrolyt bilager för att skapa sfärer. Metodbygger bilager av CNF och polyelektrolyter som kan belägga ytor av olika material. Dennaavhandling fokuseradar först på att demonstrera sfärformationsförmågan vid användning avpolyelektrolyter med lågmolekylvikt i de tillverkade LbL-modifieringarna. Däreftergenomfördes en undersökning som innefattar inb, QC 20231124

In the context of three-dimensional (3D) cell culture and tissue engineering, 3D printing is a powerful tool for customizing in vitro 3D cell culture models that are critical for understanding the cell-matrix and cell-cell interactions. Cellulose nanofibril (CNF) hydrogels are emerging in constructing scaffolds able to imitate tissue in a microenvironment. A direct modification of the methacryloyl (MA) group onto CNF is an appealing approach to synthesize photocross-linkable building blocks in formulating CNF-based bioinks for light-assisted 3D printing; however, it faces the challenge of the low efficiency of heterogenous surface modification. Here, a multistep approach yields CNF methacrylate (CNF-MA) with a decent degree of substitution while maintaining a highly dispersible CNF hydrogel, and CNF-MA is further formulated and copolymerized with monomeric acrylamide (AA) to form a super transparent hydrogel with tuneable mechanical strength (compression modulus, approximately 5-15 kPa). The resulting photocurable hydrogel shows good printability in direct ink writing and good cytocompatibility with HeLa and human dermal fibroblast cell lines. Moreover, the hydrogel reswells in water and expands to all directions to restore its original dimension after being air-dried, with further enhanced mechanical properties, for example, Young’s modulus of a 1.1% CNF-MA/1% PAA hydrogel after reswelling in water increases to 10.3 kPa from 5.5 kPa., QC 20231115

In cases of blinding disease or trauma, hydrogels have been proposed as scaffolds for corneal regenera-tion and vehicles for ocular drug delivery. Restoration of corneal transparency, augmenting a thin cornea and postoperative drug delivery are particularly challenging in resource-limited regions where drug avail-ability and patient compliance may be suboptimal. Here, we report a bioengineered hydrogel based on porcine skin collagen as an alternative to human donor corneal tissue for applications where long-term stability of the hydrogel is required. The hydrogel is reinforced with cellulose nanofibers extracted from the Ciona intestinalis sea invertebrate followed by double chemical and photochemical crosslinking. The hydrogel is additionally loaded with dexamethasone to provide sustained anti-inflammatory activity. The reinforced double-crosslinked hydrogel after drug loading maintained high optical transparency with sig-nificantly improved mechanical characteristics compared to non-reinforced hydrogels, while supporting a gradual sustained drug release for 60 days in vitro . Dexamethasone, after exposure to crosslinking and sterilization procedures used in hydrogel production, inhibited tube formation and cell migration of TNF alpha-stimulated vascular endothelial cells. The drug-loaded hydrogels suppressed key pro-inflammatory cytokines CCL2 and CXCL5 in TNF alpha-stimulated human corneal epithelial cells. Eight weeks after intra-stromal implantation in the cornea of 12 New-Zealand white rabbits subjected to an inflammatory suture stimulus, the dexamethasone-releasing hydrogels suppressed TNF alpha, MMP-9, and leukocyte and fibrob-last cell invasion, resulting in reduced corneal haze, sustained corneal thickness and stromal morphology, and reduced overall vessel invasion. This collagen-nanocellulose double-crosslinked hydrogel can be im-planted to treat corneal stromal disease while suppressing inflammation and maintaining transparency after corneal transplantat, Funding Agencies|European Commission [667400]; LinkoCare Life Sciences AB; NaturaLens AB

Three-dimensional (3D) tumor spheroids are regarded as promising models for utilization as preclinical assessments of chemo-sensitivity. However, the creation of these tumor spheroids presents challenges, given that not all tumor cell lines are able to form consistent and regular spheroids. In this context, we have developed a novel layer-by-layer coating of cellulose nanofibril–polyelectrolyte bilayers for the generation of spheroids. This technique builds bilayers of cellulose nanofibrils and polyelectrolytes and is used here to coat two distinct 96-well plate types: nontreated/non-sterilized and Nunclon Delta. In this work, we optimized the protocol aimed at generating and characterizing spheroids on difficult-to-grow pancreatic tumor cell lines. Here, diverse parameters were explored, encompassing the bilayer count (five and ten) and multiple cell-seeding concentrations (10, 100, 200, 500, and 1000 cells per well), using four pancreatic tumor cell lines—KPCT, PANC-1, MiaPaCa-2, and CFPAC-I. The evaluation includes the quantification (number of spheroids, size, and morphology) and proliferation of the produced spheroids, as well as an assessment of their viability. Notably, our findings reveal a significant influence from both the number of bilayers and the plate type used on the successful formation of spheroids. The novel and simple layer-by-layer-based coating method has the potential to offer the large-scale production of spheroids across a spectrum of tumor cell lines., QC 20231215

QC 20231127

Mechanical loading has been described as having the potential to affect bone growth. In order to experimentally study the potential clinical applications of mechanical loading as a novel treatment to locally modulate bone growth, there is a need to develop a portable mechanical loading device enabling studies in small bones. Existing devices are bulky and challenging to transfer within and between laboratories and animal facilities, and they do not offer user-friendly mechanical testing across both ex vivo cultured small bones and in vivo animal models. To address this, we developed a portable loading device comprised of a linear actuator fixed within a stainless-steel frame equipped with suitable structures and interfaces. The actuator, along with the supplied control system, can achieve high-precision force control within the desired force and frequency range, allowing various load application scenarios. To validate the functionality of this new device, proof-of-concept studies were performed in ex vivo cultured rat bones of varying sizes. First, very small fetal metatarsal bones were microdissected and exposed to 0.4 N loading applied at 0.77 Hz for 30 s. When bone lengths were measured after 5 days in culture, loaded bones had grown less than unloaded controls (p < 0.05). Next, fetal rat femur bones were periodically exposed to 0.4 N loading at 0.77 Hz while being cultured ex vivo for 12 days. Interestingly, this loading regimen had the opposite effect on bone growth, i.e., loaded femur bones grew significantly more than unloaded controls (p < 0.001). These findings suggest that complex relationships between longitudinal bone growth and mechanical loading can be determined using this device. We conclude that our new portable mechanical loading device allows experimental studies in small bones of varying sizes, which may facilitate further preclinical studies exploring the potential clinical applications of mechanical loading., QC 20231107

Bioprinting of hydrogel-based bioinks can allow for thefabricationof elaborate, cell-laden 3D structures. In addition to providing anadequate extracellular matrix mimetic environment and high cell viability,the hydrogels must offer facile extrusion through the printing nozzleand retain the shape of the printed structure. We demonstrate a strategyto incorporate cellulose oxalate nanofibrils in hyaluronan-based hydrogelsto generate shear thinning bioinks that allowed for printing of free-standingmultilayer structures, covalently cross-linked after bioprinting,yielding long-term stability. The storage modulus of the hydrogelswas tunable between 0.5 and 1.5 kPa. The nanocellulose containinghydrogels showed good biocompatibility, with viability of primaryhuman dermal fibroblasts above 80% at day 7 after seeding. The cellswere also shown to tolerate the printing process well, with viabilityabove 80% 24 h after printing. We anticipate that this hydrogel systemcan find broad use as a bioink to produce complex geometries thatcan support cell growth., Funding Agencies|Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University [2009-00971]; Carl Tryggers Foundation; Knut and Alice Wallenberg Foundation [KAW 2016.0231, 2021.0186]

Silicon nitride (SiN) coatings may reduce unwanted release of metal ions from metallic implants. However, as SiN slowly dissolves in aqueous solutions, additives that reduce this dissolution rate would likely increase the lifetime and functionality of implants. Adding iron (Fe) and carbon (C) permits tuning of the SiN coatings’ mechanical properties, but their effect on SiN dissolution rates, and their capacity to reduce metal ion release from metallic implant substrates, have yet to be investigated. Such coatings have recently been proposed for use in spinal implants; therefore, it is relevant to assess their impact on the viability of cells expected at the implant site, such as microglia, the resident macrophages of the central nervous system (CNS). To study the effects of Fe and C on the dissolution rate of SiN coatings, compositional gradients of Si, Fe and C in combination with N were generated by physical vapor deposition onto CoCrMo discs. Differences in composition did not affect the surface roughness or the release of Si, Fe or Co ions (the latter from the CoCrMo substrate). Adding Fe and C reduced ion release compared to a SiN reference coating, which was attributed to altered reactivity due to an increase in the fraction of stabilizing Si–C or Fe–C bonds. Extracts from the SiN coatings containing Fe and C were compatible with microglial viability in 2D cultures and 3D collagen hydrogels, to a similar degree as CoCrMo and SiN coated CoCrMo reference extracts. As Fe and C reduced the dissolution rate of SiN-coatings and did not compromise microglial viability, the capacity of these additives to extend the lifetime and functionality of SiN-coated metallic implants warrants further investigation.

Oxide-derived copper (OD-Cu) is the most efficient and likely practical electrocatalyst for CO2 reduction toward multicarbon products. However, the inevitable but poorly understood reconstruction from the pristine state to the working state of OD-Cu under strong reduction conditions largely hinders the rational construction of catalysts toward multicarbon products, especially C-3 products like n-propanol. Here, we simulate the reconstruction of CuO and Cu2O into their derived Cu by molecular dynamics, revealing that CuO-derived Cu (CuOD-Cu) intrinsically has a richer population of undercoordinated Cu sites and higher surficial Cu atom density than the counterpart Cu2O-derived Cu (Cu2OD-Cu) because of the vigorous oxygen removal. In situ spectroscopes disclose that the coordination number of CuOD-Cu is considerably lower than that of Cu2OD-Cu, enabling the fast kinetics of CO2 reaction and strengthened binding of *C-2 intermediate(s). Benefiting from the rich undercoordinated Cu sites, CuOD-Cu achieves remarkable n-propanol faradaic efficiency up to similar to 17.9%, whereas the Cu2OD-Cu dominantly generates formate.

3D bioprinting allows for the manufacturing of tissue-like structures that could be used for culturing and studying cells in a microenvironment representative of the cell’s natural environment. In recent years, hydrogel bioinks from different biomaterials have been in development and utilized in tissue engineering applications. The most common biomaterial is collagen, the main component of the ECM, due to its high biocompatibility. However, collagen bioinks have poor mechanical properties, limiting their use for bioprinting without addition of chemical crosslinks. Efforts have been made in attempts to overcome these issues. In this project collagen hydrogels of high concentration derived from decellularized ECM of rat tail tendons were developed and examined for future use as bioink. After decellularization, the dECM was translated into pre-gels of varying concentrations and exposure to pepsin, to see how this would affect the gelation kinetics and rheological properties. The biochemical profile of the pre-gel consisted of collagen type 1 and various glycosaminoglycans. The pre-gels displayed promising rheological properties for direct printing. Regardless of concentration and pepsin exposure, the pre-gel displayed shear thinning behavior and gelation below 10 min. Increasing the concentration of the hydrogels, increased the storage modulus from 1 kPa to 10 kPA. Increasing the concentration, also affected the gelation temperature to below 37 °C. However, cells could not be cultured within the hydrogels. Further research would need to be done in order to evaluate the cell compatibility of the pre-gels and suitable printing approaches

Surgical site infections (SSI) are a clinical and economic burden. Suture-associated SSI may develop when bacteria colonize the suture surface and form biofilms that are resistant to antibiotics. Thrombin-derived C-terminal peptide (TCP)-25 is a host defense peptide with a unique dual mode of action that can target both bacteria and the excessive inflammation induced by bacterial products. The peptide demonstrates therapeutic potential in preclinical in vivo wound infection models. In this study, the authors set out to explore whether TCP-25 can provide a new bioactive innate immune feature to hydrophilic polyglactin sutures (Vicryl). Using a combination of biochemical, biophysical, antibacterial, biofilm, and anti-inflammatory assays in vitro, in silico molecular modeling studies, along with experimental infection and inflammation models in mice, a proof-of-concept that TCP-25 can provide Vicryl sutures with a previously undisclosed host defense capacity, that enables targeting of bacteria, biofilms, and the accompanying inflammatory response, is shown.

Calcium phosphates (CaP) represent an important class of osteoconductive and osteoinductive biomaterials. As proof-of-concept, we show how a multi-component CaP formulation (monetite, beta-tricalcium phosphate, and calcium pyrophosphate) guides osteogenesis beyond the physiological envelope. In a sheep model, hollow dome-shaped constructs were placed directly over the occipital bone. At 12 months, large amounts of bone (similar to 75%) occupy the hollow space with strong evidence of ongoing remodelling. Features of both compact bone (osteonal/osteon-like arrangements) and spongy bone (trabeculae separated by marrow cavities) reveal insights into function/need-driven microstructural adaptation. Pores within the CaP also contain both woven bone and vascularised lamellar bone. Osteoclasts actively contribute to CaP degradation/removal. Of the constituent phases, only calcium pyrophosphate persists within osseous (cutting cones) and non-osseous (macrophages) sites. From a translational perspective, this multi-component CaP opens up exciting new avenues for osteotomy-free and minimally-invasive repair of large bone defects and augmentation of the dental alveolar ridge.

Background: Surface compatibility with blood is critical both for scientific investigations on hemostasis and clinical applications. Regarding in vitro and ex vivo investigations, minimal alteration in physiological hemostasis is of particular importance to draw reliable conclusions on the human coagulation system. At the same time, artificial coagulation activation must be avoided, which is relevant for the patient, for example to prevent stent graft occlusion. The aim was to evaluate the advantages and disadvantages of antithrombotic and antifouling surface coatings in the context of their suitability for ex vivo incubation and the study of coagulation properties. Methods: We investigated the impact of different protocols for surface coating of synthetic material and different anticoagulants on hemostasis and platelet activation in ex vivo human whole blood.Blood samples from healthy donors were incubated in coated microtubes on a rotating wheel at 37 degrees C. Two protocols for surface coating were analyzed for hemostatic parameters and metabolic status, a heparin-based coating (CHC, Corline Heparin Conjugate) without further anticoagulation and a passivating coating (MPC, 2-methacryloyloxethyl phosphorylcholine) with added anticoagulants (enoxaparin, ENOX; or fondaparinux, FPX). Employing the MPC-based coating, the anticoagulants enoxaparin and fondaparinux were compared regarding their differential effects on plasmatic coagulation by thrombelastometry and on platelet activation by flowcytometry and platelet function assays. Results: Using the CHC coating, significant coagulation cascade activation was observed, whereas parameters remained mostly unchanged with MPC-based protocols. Extended incubation caused significantly elevated levels of the soluble membrane attack complex. Neither ENOX nor FPX caused a relevant impairment of platelet function or activation capacity and thrombelastometric parameters remained unchanged with both protocols. For translational p

INTRODUCTION: Wear and corrosion may lead to a release of particles and ions from spinal implants, which is a concern because of their potentially detrimental effect on the life span of the implant [1]. Silicon nitride-based coatings have been suggested as an option to reduce the release of metal ions from an implant. In addition, any particles produced will slowly dissolve, releasing only biocompatible ions [2]. It is of high interest to reduce the dissolution rate of the coating to ensure an adequate lifetime [3]. The present study aimed to assess the effect of Fe and C additions to silicon nitride coatings in terms of dissolution rate as well as the impact of the released ions on the in vitro neural cell response. METHODS: Using a combinatorial approach, SiFeCN coatings were deposited on CoCr disc substrates by reactive sputtering in an in-house built equipment. The coatings were characterized in 9 points using x-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). The dissolution behaviour was evaluated by exposing the coated samples to cell media for 14 days. The obtained extracts were used to measure ion release with inductively coupled plasma - optical emission spectrometry (ICP-OES) and to assess cell viability of microglia (C8-B4 cell line) using the MTT assay. RESULTS: The XPS results showed compositional gradients of Si ranging from 35.0 to 47.3 at.%, Fe from 1.4 to 9.3 at.% and C from 4.5 to 13.9 at.%. SEM of focused ion beam (FIB) cross-sections revealed coating thicknesses between 427-534 nm. SEM of the coating after exposure showed substantial signs of dissolution with visibly increased porosity for the SiN coating, while the SiFeCN coatings appeared less affected. SiFeCN coatings appeared more affected by dissolution for increasing Si contents. The estimated dissolution rate of the SiN coating was 8.3 nm/day, while the rate of SiFeCN coatings was 5.2-6.8 nm/day. The ICP results showed a reduction in Co ions from the substrate

OBJECTIVE: Cranioplasty with synthetic implant can be performed to restore function and form of the skull after resection of malignancy infiltrating the bone. The aim of this study was to examine the rate of implant failure and tumor recurrence in patients undergoing nonautologous cranioplasty and tumor resection. METHODS: In this retrospective single-center study, 48 patients were identified who had undergone cranioplasty with synthetic implants after tumor resection between 2010 and 2020. The medical records were analyzed to investigate patient demographics, surgery data, cranioplasty failure rates, and rate of tumor recurrence. RESULTS: Cranioplasty failed in 8 patients. The median time to implant failure was 220 days with most failures occurring within 1 year (5 of 8). There was no significant difference in rate or time to failure between the different cranioplasty materials (P = 0.39). Low body mass index (P < 0.05), previous craniectomy/cranioplasty (P < 0.05), previous radiation therapy to the brain/skull (P < 0.05), and skin closure with sutures (P < 0.05) were associated with an increased risk of implant failure. Tumors recurred in 15 patients. CONCLUSIONS: Cranioplasty surgery with synthetic implants carries a relatively high risk of failure, regardless of type of cranioplasty material used. Skin closure with staples may be beneficial in these patients.

Biodegradable metals are being investigated as temporary implants that dissolve safely in the body after bone regeneration. Zinc (Zn) has an intermediate biodegradation rate between magnesium and stainless steels, yet its degradation rate is too slow to function as a temporary orthopedic implant. Alloying with nutrient elements is considered a strategy to tune its mechanical properties and in vivo biodegradability. Zn/calcium (Zn/Ca) alloys (with 0.5, 1, and 2 wt% Ca) were processed by spark plasma sintering and their microstructure, mechanical, and biodegradation properties were investigated. Ca was distributed in the grain boundary regions of Zn due to its low miscibility in Zn. Furthermore, the corrosion rates of Zn/Ca alloys determined from linear polarization measurements (0.164–0.325 mm/yr) accelerated by at least 10% compared with pure sintered Zn (0.149 mm/yr) with simultaneous dissolution of Zn and Ca, as verified from X-ray diffraction analysis of the corrosion products. The alloy specimens exhibited hardness (52–58 HV) and compressive strength (93–119 MPa) comparable with those of human cortical and cancellous bones (49 HV; 90–209 MPa). This study demonstrated the tunability of the mechanical and biodegradation properties of Zn-based materials by alloying them with a nutrient element for potential application as temporary orthopedic implants., Validerad;2023;Nivå 2;2023-03-08 (joosat);Funder: National Natural Science Foundation of China (No.52020105011)Licens fulltext: CC BY License

The skin is the largest organ of the human body. Wounds disrupt the functions of the skin and can have catastrophic consequences for an individual resulting in significant morbidity and mortality. Wound infections are common and can substantially delay healing and can result in non-healing wounds and sepsis. Early diagnosis and treatment of infection reduce risk of complications and support wound healing. Methods for monitoring of wound pH can facilitate early detection of infection. Here we show a novel strategy for integrating pH sensing capabilities in state-of-the-art hydrogel-based wound dressings fabricated from bacterial nanocellulose (BC). A high surface area material was developed by self-assembly of mesoporous silica nanoparticles (MSNs) in BC. By encapsulating a pH-responsive dye in the MSNs, wound dressings for continuous pH sensing with spatiotemporal resolution were developed. The pH responsive BC-based nanocomposites demonstrated excellent wound dressing properties, with respect to conformability, mechanical properties, and water vapor transmission rate. In addition to facilitating rapid colorimetric assessment of wound pH, this strategy for generating functional BC-MSN nanocomposites can be further be adapted for encapsulation and release of bioactive compounds for treatment of hard-to-heal wounds, enabling development of novel wound care materials., Validerad;2023;Nivå 2;2023-03-03 (hanlid);Funder: Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linköping University (SFO-Mat-LiU no. 2009–00971)

Cardiovascular diseases are currently the leading cause of death globally. Progression of the disease affects the composition and function of the heart and in many cases subsequently results in heart failure over time where a heart transplant is vital. Therefore, there is a need for medical treatments to stop the progression of the disease. Hydrogels as a biomaterial have been investigated for this purpose, but most known research to date has focused on their bioactive properties. Since a part of the disease progression is affected by the mechanical differences between myocardial tissue and the collagen the body replaces the loss of viable myocardium with after myocardial infarction, this thesis conducted a novel approach of comparing a thiol functionalized collagen hydrogel with a healthy left ventricle in terms of viscoelastic properties for tissue-bulking application. Swelling tests showed that the gel did not swell significantly over time during incubation in phosphate buffer and even if self-healing of the gel after subjection to ultrasound radiation could not be proven and previously used methods to obtain mechanical stiffness of a tissue (compression tests) could not be utilized for soft materials such as hydrogels, the material is of great interest as a candidate for tissue bulking purposes. The gel showed viscoelastic properties similar to the healthy left ventricle and was injectable, to be administrated in a minimally invasive manner, indicating that the material could act as a tissue-bulking agent. This project has developed a new approach to evaluating hydrogels as a biomaterial by comparing it to the viscoelastic characterization of the intended application tissue.

Injectable hydrogels show great promise in developingnovel regenerativemedicine solutions and present advantages for minimally invasive applications.Hydrogels based on extracellular matrix components, such as collagen,have the benefits of cell adhesiveness, biocompatibility, and degradabilityby enzymes. However, to date, reported collagen hydrogels possesssevere shortcomings, such as nonbiocompatible cross-linking chemistry,significant swelling, limited range of mechanical properties, or gelationkinetics unsuitable for in vivo injection. To solvethese issues, we report the design and characterization of an injectablecollagen hydrogel based on covalently modified acetyl thiol collagencross-linked using thiol-maleimide click chemistry. The hydrogel isinjectable for up to 72 h after preparation, shows no noticeable swelling,is transparent, can be molded in situ, and retainsits shape in solution for at least one year. Notably, the hydrogelmechanical properties can be fine-tuned by simply adjusting the reactantstoichiometries, which to date was only reported for synthetic polymerhydrogels. The biocompatibility of the hydrogel is demonstrated in vitro using human corneal epithelial cells, which maintainviability and proliferation on the hydrogels for at least seven days.Furthermore, the developed hydrogel showed an adhesion strength onsoft tissues similar to fibrin glue. Additionally, the developed hydrogelcan be used as a sealant for repairing corneal perforations and canpotentially alleviate the off-label use of cyanoacrylate tissue adhesivefor repairing corneal perforations. Taken together, these characteristicsshow the potential of the thiol collagen hydrogel for future use asa prefabricated implant, injectable filler, or as sealant for cornealrepair and regeneration.

Loading bioactive molecules, such as proteins and peptides, into hydrogels is a promising strategy to expand the application of hydrogels in tissue engineering. Herein, a novel bioactive gelatin hydrogel loading peptide derived from Atlantic cod (Gadus morhua) was developed for bone tissue engineering, which was constructed on the NaIO4-mediated oxidative coupling of dopamine-modified gelatin (Gel-DA). The Gel-DA hydrogel incorporated with cod peptides (0.5 mg/mL) showed an acceptable gelation time (130.22 & PLUSMN; 7.15 s) and maintained a continuous microscopic pore structure. Besides, the compression strength and adhesive strength of Gel-DA hydrogel with 0.5 mg/mL cod peptides reached 136.33 & PLUSMN; 38.95 kPa and 4.93 & PLUSMN; 0.80 kPa, respectively. Meanwhile, all hydrogels exhibited excellent mechanical stability. The incorporation of cod peptides (0.1, 0.5 mg/mL) was beneficial to the adhesion and spreading of mouse osteoblasts precursor cells MC3T3-E1. Moreover, the alkaline phosphatase (ALP) activity of the Gel-DA hydrogel loading 0.5 mg/mL peptides was significantly increased from 0.16 & PLUSMN; 0.02 U.mg/protein to 0.19 & PLUSMN; 0.02 U.mg/protein as compared to Gel-DA hydrogel. These results indicated that the GD-CPs hydrogel is an effective candidate material for bone tissue engineering.

Spinal implants have been used for decades to treat different spinal conditions. However, certain implant-related complications have been attributed to the release of particles and ions due to corrosion and wear triggering local immune responses including the release of pro-inflammatory cytokines, leading to local inflammation. The impact of these particles and ions on cells from the central nervous system (CNS) remains largely unknown, with few studies examining the effects on glial cells1. Indeed, the particles may migrate to adjacent nervous tissues and increasing our knowledge of the glial cell response is essential since they play a crucial role in maintaining tissue homeostasis and protecting the CNS. Most prior studies have used traditional 2D culture models; however, these lack the 3D spatial arrangement of cells found in tissues where they form important interactions with the extracellular matrix. The aim of this study was to employ an open source bioprinter2 to extrude hydrogels containing glial cells into which experimental implant debris can be introduced, enabling monitoring of cell viability and inflammatory responses by fluorescence microscopy. We have previously established that mono-cultures of microglia and astrocytes can be 3D cultured in collagen hydrogels, and their viability monitored using the caspase-3/7 apoptosis reporter and propidium iodide labelling for cell death. Applying a bioprinting strategy to produce these glial-laden constructs increases the reproducibility of these models, and allows the study of a wide range of types and concentrations of particles, resulting in a valuable tool to increase the knowledge about the biological response generated by particles from spinal implants.

The present study investigated early interactions between three alloplastic materials (calcium phosphate (CaP), titanium alloy (Ti), and polyetheretherketone (PEEK) with human whole blood using an established in vitro slide chamber model. After 60 min of contact with blood, coagulation (thrombin-antithrombin complexes, TAT) was initiated on all test materials (Ti > PEEK > CaP), with a significant increase only for Ti. All materials showed increased contact activation, with the KK-AT complex significantly increasing for CaP (p < 0.001), Ti (p < 0.01), and PEEK (p < 0.01) while only CaP demonstrated a notable rise in KK-C1INH production (p < 0.01). The complement system had significant activation across all materials, with CaP (p < 0.0001, p < 0.0001) generating the most pronounced levels of C3a and sC5b-9, followed by Ti (p < 0.001, p < 0.001) and lastly, PEEK (p < 0.001, p < 0.01). This activation correlated with leukocyte stimulation, particularly myeloperoxidase release. Consequently, the complement system may assume a more significant role in the early stages post implantation in response to CaP materials than previously recognized. Activation of the complement system and the inevitable activation of leukocytes might provide a more favorable environment for tissue remodeling and repair than has been traditionally acknowledged. While these findings are limited to the early blood response, complement and leukocyte activation suggest improved healing outcomes, which may impact long-term clinical outcomes.

Biological materials such as cell-derived membrane vesicles have emerged as alternative sources for molecular delivery systems, owing to multicomponent features, the inherent functionalities and signaling networks, and easy-to-carry therapeutic agents with various properties. Herein, red blood cell membrane (RBCM) vesicle-laden methacrylate kappa-carrageenan (KaMA) composite hydrogel is introduced for soft tissue engineering. Results revealed that the characteristics of hybrid hydrogels were significantly modulated by changing the RBCM vesicle content. For instance, the incorporation of 20% (v/v) RBCM significantly enhanced compressive strength from 103 & PLUSMN; 26 kPa to 257 & PLUSMN; 18 kPa and improved toughness under the cyclic loading from 1.0 & PLUSMN; 0.4 kJ m(-3) to 4.0 & PLUSMN; 0.5 kJ m(-3) after the 5(th) cycle. RBCM vesicles were also used for the encapsulation of curcumin (CUR) as a hydrophobic drug molecule. Results showed a controlled release of CUR over three days of immersion in PBS solution. The RBCM vesicles laden KaMA hydrogels also supported in vitro fibroblast cell growth and proliferation. In summary, this research sheds light on KaMA/RBCM hydrogels, that could reveal fine-tuned properties and hydrophobic drug release in a controlled manner.

Exosomes (diameter 30-200 nm) are a subtype of extracellular vesicles secreted by cells containing DNA, microRNA (miRNA), and proteins. Exosomes are expected to be valuable as a means of delivering drugs or functional miRNAs in treatment of diseases. However, the delivery of exosomes is not sufficiently effective, even though exosomes have intrinsic delivery functions. Cell-penetrating peptides (CPPs) are short peptide families that facilitate cellular intake of molecules and vesicles. We previously reported that the modification of cells, and liposomes with CPP-conjugated-lipids, CPPs conjugated with poly (ethylene glycol)-conjugated phospholipids (PEG-lipid), that induce adhesion by CPPs, can be useful for cell-based assays and harvesting liposomes. In this study, we aimed to modulate the exosome surface using Tat peptide (YGRKKRRQRRR)-PEG-lipids to improve intracellular delivery to endothelial cells. We isolated and characterized exosomes from the medium of HEK 293 T cell cultures. Tat conjugated PEG -lipids with different spacer molecular weights and lipid types were incorporated into exosomes using fluorescein isothiocyanate labeling to optimize the number of Tat-PEG-lipids immobilized on the exo-some surface. The exosomes modified with Tat-PEG-lipids were incubated with human umbilical vein endothelial cells (HUVECs) to study the interaction. Tat conjugated with 5 kDa PEG and C16 lipids incorporated on the exosome surface were highly detected inside HUVECs by flow cytometry. Fluores-cence was negligible in HUVECs for control groups. Thus, Tat-PEG-lipids can be modified on the exosome surface, improving the intracellular delivery of exosomes.

Treating wound infections is a difficult task ever since pathogenic bacteria started to develop resistance to common antibiotics. The present study develops hybrid hydrogels based on the formation of a polyelectrolyte complex between the anionic charges of dopamine-functionalized Gellan Gum (GG-DA) and the cationic moieties of the TMP-G2-alanine dendrimer. The hydrogels thus obtained can be doubly crosslinked with CaCl2, obtaining solid hydrogels. Or, by oxidizing dopamine to GG-DA, possibly causing further interactions such as Schiff Base and Michael addition to take place, hydrogels called injectables can be obtained. The latter have shear-thinning and self-healing properties (efficiency up to 100%). Human dermal fibroblasts (HDF), human epidermal keratinocytes (HaCaT), and mouse monocyte cells (RAW 264.7), after incubation with hydrogels, in most cases show cell viability up to 100%. Hydrogels exhibit adhesive behavior on various substrates, including porcine skin. At the same time, the dendrimer serves to crosslink the hydrogels and endows them with excellent broad-spectrum microbial eradication activity within four hours, evaluated using Staphylococcus aureus 2569 and Escherichia coli 178. Using the same GG-DA/TMP-G2-alanine ratios hybrid hydrogels with tunable properties and potential for wound dressing applications can be produced., QC 20230911