Functionalized Gelatin/Polysaccharide Hydrogels for Encapsulation of Hepatocytes.

Liver diseases represent a considerable burden to patients and healthcare systems. Hydrogels play an important role in the engineering of soft tissues and may be useful for embedding hepatocytes for different therapeutic interventions or the development of in vitro models to study the pathogenesis of liver diseases or testing of drugs. Here, we developed two types of hydrogels by crosslinking hydrazide-functionalized gelatin with either oxidized dialdehyde hyaluronan or alginate through the formation of hydrazone bonds. Gel formulations were studied through texture analysis and rheometry, showing mechanical properties comparable to those of liver tissue while also demonstrating long-term stability. The biocompatibility of hydrogels and their ability to host hepatocytes was studied in vitro in comparison to pure gelatin hydrogels crosslinked by transglutaminase using the hepatocellular line HepG2. It was found that HepG2 cells could be successfully embedded in the hydrogels, showing no signs of gel toxicity and proliferating in a 3D environment comparable to pure transglutaminase cross-linked gelatin hydrogels used as control. Altogether, hydrazide gelatin in combination with oxidized polysaccharides makes stable in situ gelling systems for the incorporation of hepatocytes, which may pave the way for use in liver tissue engineering and drug testing.

The Combination of Bioactive Herbal Compounds with Biomaterials for Regenerative Medicine.

Regenerative medicine aims to restore the function of diseased or damaged tissues and organs by cell therapy, gene therapy, and tissue engineering, along with the adjunctive application of bioactive molecules. Traditional bioactive molecules, such as growth factors and cytokines, have shown great potential in the regulation of cellular and tissue behavior, but have the disadvantages of limited source, high cost, short half-life, and side effects. In recent years, herbal compounds extracted from natural plants/herbs have gained increasing attention. This is not only because herbal compounds are easily obtained, inexpensive, mostly safe, and reliable, but also owing to their excellent effects, including anti-inflammatory, antibacterial, antioxidative, proangiogenic behavior and ability to promote stem cell differentiation. Such effects also play important roles in the processes related to tissue regeneration. Furthermore, the moieties of the herbal compounds can form physical or chemical bonds with the scaffolds, which contributes to improved mechanical strength and stability of the scaffolds. Thus, the incorporation of herbal compounds as bioactive molecules in biomaterials is a promising direction for future regenerative medicine applications. Herein, an overview on the use of bioactive herbal compounds combined with different biomaterial scaffolds for regenerative medicine application is presented. We first introduce the classification, structures, and properties of different herbal bioactive components and then provide a comprehensive survey on the use of bioactive herbal compounds to engineer scaffolds for tissue repair/regeneration of skin, cartilage, bone, neural, and heart tissues. Finally, we highlight the challenges and prospects for the future development of herbal scaffolds toward clinical translation. Overall, it is believed that the combination of bioactive herbal compounds with biomaterials could be a promising perspective for the next generation of regenerative medicine.

The European Polysaccharide Network of Excellence (EPNOE) research roadmap 2040: Advanced strategies for exploiting the vast potential of polysaccharides as renewable bioresources.

Polysaccharides are among the most abundant bioresources on earth and consequently need to play a pivotal role when addressing existential scientific challenges like climate change and the shift from fossil-based to sustainable biobased materials. The Research Roadmap 2040 of the European Polysaccharide Network of Excellence (EPNOE) provides an expert's view on how future research and development strategies need to evolve to fully exploit the vast potential of polysaccharides as renewable bioresources. It is addressed to academic researchers, companies, as well as policymakers and covers five strategic areas that are of great importance in the context of polysaccharide related research: (I) Materials & Engineering, (II) Food & Nutrition, (III) Biomedical Applications, (IV) Chemistry, Biology & Physics, and (V) Skills & Education. Each section summarizes the state of research, identifies challenges that are currently faced, project achievements and developments that are expected in the upcoming 20 years, and finally provides outlines on how future research activities need to evolve.

On the reproducibility of extrusion-based bioprinting: round robin study on standardization in the field.

The outcome of three-dimensional (3D) bioprinting heavily depends, amongst others, on the interaction between the developed bioink, the printing process, and the printing equipment. However, if this interplay is ensured, bioprinting promises unmatched possibilities in the health care area. To pave the way for comparing newly developed biomaterials, clinical studies, and medical applications (i.e. printed organs, patient-specific tissues), there is a great need for standardization of manufacturing methods in order to enable technology transfers. Despite the importance of such standardization, there is currently a tremendous lack of empirical data that examines the reproducibility and robustness of production in more than one location at a time. In this work, we present data derived from a round robin test for extrusion-based 3D printing performance comprising 12 different academic laboratories throughout Germany and analyze the respective prints using automated image analysis (IA) in three independent academic groups. The fabrication of objects from polymer solutions was standardized as much as currently possible to allow studying the comparability of results from different laboratories. This study has led to the conclusion that current standardization conditions still leave room for the intervention of operators due to missing automation of the equipment. This affects significantly the reproducibility and comparability of bioprinting experiments in multiple laboratories. Nevertheless, automated IA proved to be a suitable methodology for quality assurance as three independently developed workflows achieved similar results. Moreover, the extracted data describing geometric features showed how the function of printers affects the quality of the printed object. A significant step toward standardization of the process was made as an infrastructure for distribution of material and methods, as well as for data transfer and storage was successfully established.

Sustained growth factor delivery from bioactive PNIPAM-grafted-chitosan/heparin multilayers as a tool to promote growth and migration of cells.

Delivery of growth factors (GFs) is challenging for regulation of cell proliferation and differentiation due to their rapid inactivation under physiological conditions. Here, a bioactive polyelectrolyte multilayer (PEM) is engineered by the combination of thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) and glycosaminoglycans to be used as reservoir for GF storage. PNIPAM-grafted-chitosan (PChi) with two degrees of substitution (DS) are synthesized, namely LMW* (DS 0.14) and HMW (DS 0.03), by grafting low (2 kDa) and high (10 kDa) molecular weight of PNIPAM on the backbone of chitosan (Chi) to be employed as polycations to form PEM with the polyanion heparin (Hep) at pH 4. Subsequently, PEMs are chemically crosslinked to improve their stability at physiological pH 7.4. Resulting surface and mechanical properties indicate that PEM containing HMW is responsive to temperature at 20 °C and 37 °C, while LMW is not. More importantly, Hep as terminal layer combined with HMW allows not only a better retention of the adhesive protein vitronectin but also a sustained release of FGF-2 at 37 °C. With the synergistic effect of vitronectin and matrix-bound FGF-2, significant promotion on adhesion, proliferation, and migration of 3T3 mouse embryonic fibroblasts is achieved on HMW-containing PEM compared to Chi-containing PEM and exogenously added FGF-2. Thus, PEM containing PNIPAM in combination with bioactive glycosaminoglycans like Hep represents a versatile approach to fabricate a GF delivery system for efficient cell culture, which can be potentially served as cell culture substrate for production of (stem) cells and bioactive wound dressing for tissue regeneration.

Fabrication of Insoluble Elastin by Enzyme-Free Cross-Linking.

Elastin is an essential extracellular matrix protein that enables tissues and organs such as arteries, lungs, and skin, which undergo continuous deformation, to stretch and recoil. Here, an approach to fabricating artificial elastin with close-to-native molecular and mechanical characteristics is described. Recombinantly produced tropoelastin are polymerized through coacervation and allysine-mediated cross-linking induced by pyrroloquinoline quinone (PQQ). A technique that allows the recovery and repeated use of PQQ for protein cross-linking by covalent attachment to magnetic Sepharose beads is developed. The produced material closely resembles natural elastin in its molecular, biochemical, and mechanical properties, enabled by the occurrence of the cross-linking amino acids desmosine, isodesmosine, and merodesmosine. It possesses elevated resistance against tryptic proteolysis, and its Young's modulus ranging between 1 and 2 MPa is similar to that of natural elastin. The approach described herein enables the engineering of mechanically resilient, elastin-like materials for biomedical applications.

Research Progress in Enzymatically Cross-Linked Hydrogels as Injectable Systems for Bioprinting and Tissue Engineering.

Hydrogels have been developed for different biomedical applications such as in vitro culture platforms, drug delivery, bioprinting and tissue engineering. Enzymatic cross-linking has many advantages for its ability to form gels in situ while being injected into tissue, which facilitates minimally invasive surgery and adaptation to the shape of the defect. It is a highly biocompatible form of cross-linking, which permits the harmless encapsulation of cytokines and cells in contrast to chemically or photochemically induced cross-linking processes. The enzymatic cross-linking of synthetic and biogenic polymers also opens up their application as bioinks for engineering tissue and tumor models. This review first provides a general overview of the different cross-linking mechanisms, followed by a detailed survey of the enzymatic cross-linking mechanism applied to both natural and synthetic hydrogels. A detailed analysis of their specifications for bioprinting and tissue engineering applications is also included.

3D printed neural tissues with in situ optical dopamine sensors.

Engineered neural tissues serve as models for studying neurological conditions and drug screening. Besides observing the cellular physiological properties, in situ monitoring of neurochemical concentrations with cellular spatial resolution in such neural tissues can provide additional valuable insights in models of disease and drug efficacy. In this work, we demonstrate the first three-dimensional (3D) tissue cultures with embedded optical dopamine (DA) sensors. We developed an alginate/Pluronic F127 based bio-ink for human dopaminergic brain tissue printing with tetrapodal-shaped-ZnO microparticles (t-ZnO) additive as the DA sensor. DA quenches the autofluorescence of t-ZnO in physiological environments, and the reduction of the fluorescence intensity serves as an indicator of the DA concentration. The neurons that were 3D printed with the t-ZnO showed good viability, and extensive 3D neural networks were formed within one week after printing. The t-ZnO could sense DA in the 3D printed neural network with a detection limit of 0.137 µM. The results are a first step toward integrating tissue engineering with intensiometric biosensing for advanced artificial tissue/organ monitoring.

Lipoplex-Functionalized Thin-Film Surface Coating Based on Extracellular Matrix Components as Local Gene Delivery System to Control Osteogenic Stem Cell Differentiation.

A gene-activated surface coating is presented as a strategy to design smart biomaterials for bone tissue engineering. The thin-film coating is based on polyelectrolyte multilayers composed of collagen I and chondroitin sulfate, two main biopolymers of the bone extracellular matrix, which are fabricated by layer-by-layer assembly. For further functionalization, DNA/lipid-nanoparticles (lipoplexes) are incorporated into the multilayers. The polyelectrolyte multilayer fabrication and lipoplex deposition are analyzed by surface sensitive analytical methods that demonstrate successful thin-film formation, fibrillar structuring of collagen, and homogenous embedding of lipoplexes. Culture of mesenchymal stem cells on the lipoplex functionalized multilayer results in excellent attachment and growth of them, and also, their ability to take up cargo like fluorescence-labelled DNA from lipoplexes. The functionalization of the multilayer with lipoplexes encapsulating DNA encoding for transient expression of bone morphogenetic protein 2 induces osteogenic differentiation of mesenchymal stem cells, which is shown by mRNA quantification for osteogenic genes and histochemical staining. In summary, the novel gene-functionalized and extracellular matrix mimicking multilayer composed of collagen I, chondroitin sulfate, and lipoplexes, represents a smart surface functionalization that holds great promise for tissue engineering constructs and implant coatings to promote regeneration of bone and other tissues.

Wearable and implantable artificial kidney devices for end-stage kidney disease treatment: Current status and review.

BACKGROUND: Chronic kidney disease (CKD) is a major cause of early death worldwide. By 2030, 14.5 million people will have end-stage kidney disease (ESKD, or CKD stage 5), yet only 5.4 million will receive kidney replacement therapy (KRT) due to economic, social, and political factors. Even for those who are offered KRT by various means of dialysis, the life expectancy remains far too low. OBSERVATION: Researchers from different fields of artificial organs collaborate to overcome the challenges of creating products such as Wearable and/or Implantable Artificial Kidneys capable of providing long-term effective physiologic kidney functions such as removal of uremic toxins, electrolyte homeostasis, and fluid regulation. A focus should be to develop easily accessible, safe, and inexpensive KRT options that enable a good quality of life and will also be available for patients in less-developed regions of the world. CONCLUSIONS: Hence, it is required to discuss some of the limits and burdens of transplantation and different techniques of dialysis, including those performed at home. Furthermore, hurdles must be considered and overcome to develop wearable and implantable artificial kidney devices that can help to improve the quality of life and life expectancy of patients with CKD.

The Signaling Pathways Induced by Exosomes in Promoting Diabetic Wound Healing: A Mini-Review.

Impaired healing of diabetic wounds harms patients' quality of life and even leads to disability and death, which is an urgent issue to be solved clinically. Despite the great progress that has been achieved, it remains a worldwide challenge to develop effective therapeutic treatments for diabetic wounds. Recently, exosomes have attracted special attention because they can be involved in immune response, antigen presentation, cell migration, cell differentiation, tumor invasion and other processes. Meanwhile, exosomes have been proven to hold great potential in the treatment of diabetic wounds. Mechanistic studies of exosomes based on signaling pathways could not only help to uncover the mechanisms by which exosomes promote diabetic wound healing but could also provide a theoretical basis for the clinical application of exosomes. Herein, our mini-review aims to summarize the progress of research on the use of various exosomes derived from different cell types to promote diabetic wound healing, with a focus on the classical signaling pathways, including PI3K/Akt, Wnt, NF-κB, MAPK, Notch, Nrf2, HIF-1α/VEGF and TGF-ß/Smad. The results show that exosomes could regulate these signaling pathways to down-regulate inflammation, reduce oxidative stress, increase angiogenesis, promote fibroblast proliferation, induce re-epithelization and inhibit scar formation, making exosomes attractive candidates for the treatment of diabetic wounds.

Synthesis of Thermoresponsive PNIPAM-Grafted Cellulose Sulfates for Bioactive Multilayers via Layer-by-Layer Technique.

The robust thermoresponsive and bioactive surfaces for tissue engineering by combining poly-N-isopropylacrylamide (PNIPAM) and cellulose sulfate (CS) remain highly in demand but not yet realized. Herein, PNIPAM-grafted cellulose sulfates (PCSs) with diverse degrees of substitution ascribed to sulfate groups (DSS) are synthesized for the first time. Higher sulfated PCS2 generally forms larger aggregates than lower sulfated PCS1 at their cloud point temperatures (TCP) of around 33 °C, whereas PCS1 leads to larger aggregates at body temperature (37 °C). Via the layer-by-layer (LbL) technique, biocompatible polyelectrolyte multilayers (PEMs) composed of PCSs as polyanions in combination with poly-l-lysine (PLL) or quaternized chitosan (QCHI) as polycations were fabricated. The resulting surfaces contained a more intermingled structure of polyanions with both polycations, while higher sulfated cellulose derivatives (CS2 and PCS2) displayed greater stability. Studies on toxicity and biocompatibility of PEM using 3T3 mouse fibroblasts showed a lower cytotoxicity of PEM with PCS2 and CS2 than PCS1 and CS1. Furthermore, the PEM using PCS2 particularly in combination with QCHI demonstrated excellent biocompatibility that is promising for new bioactive, thermoresponsive coatings on biomaterials and substrata for culturing adhesion-dependent cells.

Free-standing multilayer films as growth factor reservoirs for future wound dressing applications.

Chronic skin wounds place a high burden on patients and health care systems. The use of angiogenic and mitogenic growth factors can facilitate the healing but growth factors are quickly inactivated by the wound environment if added exogenously. Here, free-standing multilayer films (FSF) are fabricated from chitosan and alginate as opposing polyelectrolytes in an alternating manner using layer-by-layer technique. One hundred bilayers form an about 450 µm thick, detachable free-standing film that is subsequently crosslinked by either ethyl (dimethylaminopropyl) carbodiimide combined with N-hydroxysuccinimide (E-FSF) or genipin (G-FSF). The characterization of swelling, oxygen permeability and crosslinking density shows reduced swelling and oxygen permeability for both crosslinked films compared to non-crosslinked films (N-FSF). Loading of fibroblast growth factor 2 (FGF2) into the films results in a sustained release from crosslinked FSF in comparison to non-crosslinked FSF. Biocompatibility studies in vitro with human dermal fibroblasts cultured underneath the films demonstrate increased cell growth and cell migration for all films with and without FGF2. Especially G-FSF loaded with FGF2 greatly increases cell proliferation and migration. In vivo biocompatibility studies by subcutaneous implantation in mice show that E-FSF causes an inflammatory tissue response that is absent in the case of G-FSF. N-FSF also represents a biocompatible film but shows early degradation. All FSF possess antibacterial properties against gram+ and gram- bacteria demonstrated by an agar diffusion disc assay. In summary, FSF made of alginate and chitosan crosslinked with genipin can act as a reservoir for the sustained release of FGF2, possessing high biocompatibility in vitro and in vivo. Moreover, G-FSF promotes growth and migration of human dermal fibroblasts and has antibacterial properties, which makes it an interesting candidate for bioactive wound.

Chondrogenic differentiation of mesenchymal stem cells through cartilage matrix-inspired surface coatings.

The stem cell niche comprises soluble molecules and extracellular matrix components which provide chemical and mechanical cues that determine the differentiation of stem cells. Here, the effect of polyelectrolyte multilayer (PEM) composition and terminal layer fabricated with layer-by-layer technique (LBL) pairing either hyaluronan [in its native (nHA) and oxidized form (oHA)] or chondroitin sulfate (CS) with type I collagen (Col I) is investigated on chondrogenic differentiation of human umbilical mesenchymal stem cells (hUC-MSCs). Physical studies performed to investigate the establishment and structure of the surface coatings show that PEM composed of HA and Col I show a dominance of nHA or oHA with considerably lesser organization of Col I fibrils. In contrast, distinguished fibrilized Col I is found in nCS-containing PEM. Generally, Col I-terminated PEM promote the adhesion, migration, and growth of hUC-MSCs more than GAG-terminated surfaces due to the presence of fibrillar Col I but show a lower degree of differentiation towards the chondrogenic lineage. Notably, the Col I/nHA PEM not only supports adhesion and growth of hUC-MSCs but also significantly promotes cartilage-associated gene and protein expression as found by histochemical and molecular biology studies, which is not seen on the Col I/oHA PEM. This is related to ligation of HA to the cell receptor CD44 followed by activation of ERK/Sox9 and noncanonical TGF-ß signaling-p38 pathways that depends on the molecular weight of HA as found by immune histochemical and western blotting. Hence, surface coatings on scaffolds and other implants by PEM composed of nHA and Col I may be useful for programming MSC towards cartilage regeneration.

Metal Ion Doping of Alginate-Based Surface Coatings Induces Adipogenesis of Stem Cells.

Metal ions are important effectors of protein and cell functions. Here, polyelectrolyte multilayers (PEMs) made of chitosan (Chi) and alginate (Alg) were doped with different metal ions (Ca2+, Co2+, Cu2+, and Fe3+), which can form bonds with their functional groups. Ca2+ and Fe3+ ions can be deposited in PEM at higher quantities resulting in more positive ζ potentials and also higher water contact angles in the case of Fe3+. An interesting finding was that the exposure of PEM to metal ions decreases the elastic modulus of PEM. Fourier transformed infrared (FTIR) spectroscopy of multilayers provides evidence of interaction of metal ions with the carboxylic groups of Alg but not for hydroxyl and amino groups. The observed changes in wetting and surface potential are partly related to the increased adhesion and proliferation of multipotent C3H10T1/2 fibroblasts in contrast to plain nonadhesive [Chi/Alg] multilayers. Specifically, PEMs doped with Cu2+ and Fe3+ ions greatly promote cell attachment and adipogenic differentiation, which indicates that changes in not only surface properties but also the bioactivity of metal ions play an important role. In conclusion, metal ion-doped multilayer coatings made of alginate and chitosan can promote the differentiation of multipotent cells on implants without the use of other morphogens like growth factors.

Engineering of Stable Cross-Linked Multilayers Based on Thermo-Responsive PNIPAM-Grafted-Chitosan/Heparin to Tailor Their Physiochemical Properties and Biocompatibility.

The thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) is ubiquitously applied in controlled drug release and tissue engineering. However, the lack of bioactivity of PNIPAM restricts its use in cell-containing systems being a thermo-responsive adhesive substratum with no regulating effect on cell growth and differentiation. In this study, integrating PNIPAM with chitosan into PNIPAM-grafted-chitosan (PNIPAM-Chi) allows a layer-by-layer assembly with bioactive heparin to fabricate PNIPAM-modified polyelectrolyte multilayers (PNIPAM-PEMs). Grafting PNIPAM chains of either 2 (LMW) or 10 kDa (HMW) on the chitosan backbone influences the cloud point (CP) temperature in the range from 31 to 33 °C. PNIPAM-Chi with either a higher molecular weight or a higher degree of substitution of PNIPAM chains exhibiting a significant increase in diameter above CP as ensured by dynamic light scattering is selected to fabricate PEM with heparin as a polyanion at pH 4. Little difference of layer growth is detected between the chosen PNIPAM-Chi used as polycations by surface plasmon resonance, while multilayers formed with HMW-0.02 are more hydrated and show striking swelling-and-shrinking abilities when studied with quartz crystal microbalance with dissipation monitoring. Subsequently, the multilayers are covalently cross-linked using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide to strengthen the stability of the systems under physiological conditions. Ellipsometry results confirm the layer integrity after exposure to the physiological buffer at pH 7.4 compared to those without cross-linking. Moreover, significantly higher adhesion and more spreading of C3H10T1/2 multipotent embryonic mouse fibroblasts on cross-linked PEMs, particularly with heparin terminal layers, are observed owing to the bioactivity of heparin. The slightly more hydrophobic surfaces of cross-linked PNIPAM-PEMs at 37 °C also increase cell attachment and growth. Thus, layer-by-layer constructed PNIPAM-PEM with cross-linking represents an interesting cell culture system that can be potentially employed for thermally uploading and controlled release of growth factors that further promotes tissue regeneration.

Antimicrobial and Anti-inflammatory Gallium-Defensin Surface Coatings for Implantable Devices.

Emerging and re-emerging infections are a global threat driven by the development of antimicrobial resistance due to overuse of antimicrobial agents and poor infection control practices. Implantable devices are particularly susceptible to such infections due to the formation of microbial biofilms. Furthermore, the introduction of implants into the body often results in inflammation and foreign body reactions. The antimicrobial and anti-inflammatory properties of gallium (Ga) have been recognized but not yet utilized effectively to improve implantable device integration. Furthermore, defensin (De, hBD-1) has potent antimicrobial activity in vivo as part of the innate immune system; however, this has not been demonstrated as successfully when used in vitro. Here, we combined Ga and De to impart antimicrobial activity and anti-inflammatory properties to polymer-based implantable devices. We fabricated polylactic acid films, which were modified using Ga implantation and subsequently functionalized with De. Ga-ion implantation increased surface roughness and increased stiffness. Ga implantation and defensin immobilization both independently and synergistically introduced antimicrobial activity to the surfaces, significantly reducing total live bacterial biomass. We demonstrated, for the first time, that the antimicrobial effects of De were unlocked by its surface immobilization. Ga implantation of the surface also resulted in reduced foreign body giant cell formation and expression of proinflammatory cytokine IL-1ß. Cumulatively, the treated surfaces were able to kill bacteria and reduce inflammation in comparison to the untreated control. These innovative surfaces have the potential to prevent biofilm formation without inducing cellular toxicity or inflammation, which is highly desired for implantable device integration.

Hemolytic Performance in Two Generations of the Sputnik Left Ventricular Assist Device: A Combined Numerical and Experimental Study.

BACKGROUND: Currently, left ventricular assist devices (LVADs) are a successful surgical treatment for patients with end-stage heart failure on the waiting list or with contraindicated heart transplantation. In Russia, Sputnik 1 LVAD was also successfully introduced into clinical practice as a bridge-to-transplant and a destination therapy device. Development of Sputnik 2 LVAD was aimed at miniaturization to reduce invasiveness, optimize hemocompatibility, and improve versatility for patients of various sizes. METHODS: We compared hemolysis level in flow path of the Sputnik LVADs and investigated design aspects influencing other types of blood damage, using predictions of computational fluid dynamics (CFD) and experimental assessment. The investigated operating point was a flow rate of 5 L/min and a pressure head of 100 mm Hg at an impeller rotational speed of 9100 min-1. RESULTS: Mean hemolysis indices predicted with CFD were 0.0090% in the Sputnik 1 and 0.0023% in the Sputnik 2. Averaged values of normalized index of hemolysis obtained experimentally for the Sputnik 1 and the Sputnik 2 were 0.011 ± 0.003 g/100 L and 0.004 ± 0.002 g/100 L, respectively. CONCLUSIONS: Obtained results indicate obvious improvements in hemocompatibility and sufficiently satisfy the determined miniaturization aim for the Sputnik 2 LVAD development.

Control of Blood Coagulation by Hemocompatible Material Surfaces-A Review.

Hemocompatibility of biomaterials in contact with the blood of patients is a prerequisite for the short- and long-term applications of medical devices such as cardiovascular stents, artificial heart valves, ventricular assist devices, catheters, blood linings and extracorporeal devices such as artificial kidneys (hemodialysis), extracorporeal membrane oxygenation (ECMO) and cardiopulmonary bypass. Although lower blood compatibility of materials and devices can be handled with systemic anticoagulation, its side effects, such as an increased bleeding risk, make materials that have a better hemocompatibility highly desirable, particularly in long-term applications. This review provides a short overview on the basic mechanisms of blood coagulation including plasmatic coagulation and blood platelets, as well as the activation of the complement system. Furthermore, a survey on concepts for tailoring the blood response of biomaterials to improve the hemocompatibility of medical devices is given which covers different approaches that either inhibit interaction of material surfaces with blood components completely or control the response of the coagulation system, blood platelets and leukocytes.