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In live organisms, cells are embedded in tissue-specific extracellular matrix (ECM), which provides chemical and mechanical signals important for cell differentiation, migration, and overall functionality. Careful reproduction of ECM properties in artificial cell scaffolds is necessary to get physiologically relevant results of in vitro studies and produce robust materials for cell and tissue engineering. Nanoarchitectonics is a contemporary way to building complex materials from nano-scale objects of artificial and biological origin. Decellularized ECM (dECM), remaining after cell elimination from organs, tissues and cell cultures is arguably the closest equivalent of native ECM achievable today. dECM-based materials can be used as templates or components for producing cell scaffolds using nanoarchitectonic approach. Irrespective of the form, in which dECM is used (whole acellular organ/tissue, bioink or hydrogel), the local stiffness of the dECM scaffold must be evaluated, since the fate of seeded cells depends on the mechanical properties of their environment. Careful dECM characterization is also necessary to reproduce essential ECM traits in artificial cell scaffolds by nanoparticle assembly. Atomic force microscopy (AFM) is a valuable characterization tool, as it allows simultaneous assessment of mechanical and topographic features of the scaffold, and additionally evaluate the efficiency of decellularization process and preservation of the extracellular matrix. This review depicts the current application of AFM in the field of dECM-based materials, including the basics of AFM technique and the use of flicker-noise spectroscopy (FNS) method for the quantification of the dECM micro- and nanostructure.

\nImpact StatementIn live organisms, cells are embedded in tissue-specific extracellular matrix (ECM), which provides chemical and mechanical signals important for cell differentiation, migration, and overall functionality. Careful reproduction of ECM properties in artificial cell scaffolds is necessary to get physiologically relevant results of in vitro studies and produce robust materials for cell and tissue engineering. Nanoarchitectonics is a contemporary way to building complex materials from nano-scale objects of artificial and biological origin. Decellularized ECM (dECM), remaining after cell elimination from organs, tissues and cell cultures is arguably the closest equivalent of native ECM achievable today. dECM-based materials can be used as templates or components for producing cell scaffolds using nanoarchitectonic approach. Irrespective of the form, in which dECM is used (whole acellular organ/tissue, bioink or hydrogel), the local stiffness of the dECM scaffold must be evaluated, since the fate of seeded cells depends on the mechanical properties of their environment. Careful dECM characterization is also necessary to reproduce essential ECM traits in artificial cell scaffolds by nanoparticle assembly. Atomic force microscopy (AFM) is a valuable characterization tool, as it allows simultaneous assessment of mechanical and topographic features of the scaffold, and additionally evaluate the efficiency of decellularization process and preservation of the extracellular matrix. This review depicts the current application of AFM in the field of dECM-based materials, including the basics of AFM technique and the use of flicker-noise spectroscopy (FNS) method for the quantification of the dECM micro- and nanostructure.Although several reviews on different aspects of dECM-based materials have been published recently, current applications of AFM to characterizing dECM-based scaffolds have not been summarized in specialized reviews since 2017. [ABSTRACT FROM AUTHOR]

Vascular diseases contribute to intensive and irreversible damage, and current treatments include medications, rehabilitation, and surgical interventions. Often, these diseases require some form of vascular replacement therapy (VRT) to help patients overcome life-threatening conditions and traumatic injuries annually. Current VRTs rely on harvesting blood vessels from various regions of the body like the arms, legs, chest, and abdomen. However, these procedures also produce further complications like donor site morbidity. Such common comorbidities may lead to substantial pain, infections, decreased function, and additional reconstructive or cosmetic surgeries. Vascular tissue engineering technology promises to reduce or eliminate these issues, and the existing state-of-the-art approach is based on synthetic or natural polymer tubes aiming to mimic various types of blood vessel. Burgeoning decellularization techniques are considered as the most viable tissue engineering strategy to fill these gaps. This review discusses various approaches and the mechanisms behind decellularization techniques and outlines a simplified model for a replacement vascular unit. The current state-of-the-art method used to create decellularized vessel segments is identified. Also, perspectives on future directions to engineer small- (inner diameter >1 mm and 6 mm) vessel substitutes are presented.

Featured Application: In this work, we provide a platform for nasal tissue regeneration, consisting of poly(vinyl alcohol)/gelatin sponges and mesodermal progenitor cells as a single stem cell source for connective and vascular tissues. These scaffolds show promise for application in rhinoplasty, as well as nasal tissue reconstruction following sinonasal tumor resection. Need for regeneration and repair of nasal tissues occurs as a consequence of several pathologies affecting the nose, including, but not limited to infective diseases, traumas and tumor resections. A platform for nasal tissue regeneration was set up using poly(vinyl alcohol)/gelatin sponges with 20%–30% (w/w) gelatin content to be used as scaffolds, for their intrinsic hydrophilic, cell adhesive and shape recovery properties. We propose mesodermal progenitor cells (MPCs) isolated from the bone marrow as a unique stem cell source for obtaining different connective tissues of the nose, including vascular tissue. Finally, epithelial cell immune response to these scaffolds was assessed in vitro in an environment containing inflammatory molecules. The results showed that mesenchymal stromal cells (MSCs) deriving from MPCs could be used to differentiate into cartilage and fibrous tissue; whereas, in combination with endothelial cells still deriving from MPCs, into pre-vascularized bone. Finally, the scaffold did not significantly alter the epithelial cell response to inflammatory insults derived from interaction with bacterial molecules. [ABSTRACT FROM AUTHOR]

Need for regeneration and repair of nasal tissues occurs as a consequence of several pathologies affecting the nose, including, but not limited to infective diseases, traumas and tumor resections. A platform for nasal tissue regeneration was set up using poly(vinyl alcohol)/gelatin sponges with 20%–30% (w/w) gelatin content to be used as scaffolds, for their intrinsic hydrophilic, cell adhesive and shape recovery properties. We propose mesodermal progenitor cells (MPCs) isolated from the bone marrow as a unique stem cell source for obtaining different connective tissues of the nose, including vascular tissue. Finally, epithelial cell immune response to these scaffolds was assessed in vitro in an environment containing inflammatory molecules. The results showed that mesenchymal stromal cells (MSCs) deriving from MPCs could be used to differentiate into cartilage and fibrous tissue; whereas, in combination with endothelial cells still deriving from MPCs, into pre-vascularized bone. Finally, the scaffold did not significantly alter the epithelial cell response to inflammatory insults derived from interaction with bacterial molecules.

This study aims at identifying compositional and architectural (pore size and distribution) parameters of biocompatible scaffolds, which can be best suitable for both osteoblasts and endothelial cells to produce optimized 3D cocultured constructs. Spongy scaffolds are prepared using poly(vinyl alcohol) (PVA) and gelatin (G) at different weight compositions (PVA/G range: 100/0-50/50, w/w) via emulsion and freeze-drying. The higher the gelatin content, the larger is the volume occupied by higher size pores. Human umbilical vein endothelial cells and human mesenchymal stromal cells are independently differentiated on the scaffolds to select the best candidate for the coculture. The results of metabolic activity and histology on single platforms show both cell- and material-type dependent outcomes. PVA/G 80/20 scaffolds are finally selected and allow the formation of mineralized matrix containing organized endothelial-like structures. This study highlights the need for systematic investigations on multifactorial parameters of scaffolds to improve vascularized bone substitutes. [ABSTRACT FROM AUTHOR]

Vascular diseases contribute to intensive and irreversible damage, and current treatments include medications, rehabilitation, and surgical interventions. Often, these diseases require some form of vascular replacement therapy (VRT) to help patients overcome life-threatening conditions and traumatic injuries annually. Current VRTs rely on harvesting blood vessels from various regions of the body like the arms, legs, chest, and abdomen. However, these procedures also produce further complications like donor site morbidity. Such common comorbidities may lead to substantial pain, infections, decreased function, and additional reconstructive or cosmetic surgeries. Vascular tissue engineering technology promises to reduce or eliminate these issues, and the existing state-of-the-art approach is based on synthetic or natural polymer tubes aiming to mimic various types of blood vessel. Burgeoning decellularization techniques are considered as the most viable tissue engineering strategy to fill these gaps. This review discusses various approaches and the mechanisms behind decellularization techniques and outlines a simplified model for a replacement vascular unit. The current state-of-the-art method used to create decellularized vessel segments is identified. Also, perspectives on future directions to engineer small- (inner diameter >1 mm and <6 mm) to large-caliber (inner diameter >6 mm) vessel substitutes are presented., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Chan and Corridon.)

Acute liver failure (ALF) is a dramatic clinical syndrome with high mortality because of cerebral oedema (type A hepatic encephalopathy) and multi-organ failure. With intensive care medicine and emergent liver transplantation being the mainstay of treatment, alternatives to transplantation are increasingly needed. Ammonia has been recognised as a major toxin in patients with ALF. It can be effectively removed by haemodialysis, haemofiltration and artificial liver support (a combination of extracorporeal toxin absorption and haemodialysis). Previous studies of extracorporeal detoxification, however, have either not specifically targeted ammonia or were hampered by poor biocompatibility and obsolete pathophysiological assumptions, ultimately failing to improve the prognosis. Moreover, most patients were treated only late after the emergence of advanced HE and multi-organ failure, while detoxification should prevent these complications. Acute-on-chronic liver failure (AOCLF) occurs in the setting of chronic liver disease and has an equally poor prognosis. Here, the goals of extracorporeal blood detoxification are renal support and haemodynamic stabilisation in order to support recompensation. Patients with AOCLF, unfortunately, are at a risk for treatment-related complications including bleeding, thrombocytopenia, hypotension and acute renal failure, making biocompatibility a critical issue. Peritoneal dialysis could possibly emerge as a more biocompatible way of treating refractory hepatorenal syndrome. This article will critically analyse the pathophysiological concepts and goals of extracorporeal detoxification in acute and chronic liver diseases. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To evaluate bioartificial haemodialysis access grafts in a sheep model with respect to patency and morphology. Material and methods: Bovine internal thoracic arteries (n =28) were decellularised. Fourteen grafts (DC grafts) were directly implanted as cervical AV shunts, the remaining were re-seeded with endothelial cells (ECs) derived from blood samples of the later ovine recipient (EC grafts) first. Following simulated punctures and duplex ultrasound scans to determine patency, grafts were explanted for immunohistochemical characterisation after 3 and 6 months, respectively. DC grafts underwent biomechanical testing for compliance (C), suture retention strength (SRT), and burst pressure (BP) before (n =6) and after (n =6) implantation. Results: Following 3 and 6 months, the majority of EC (n =6/6; n =6/7) and DC grafts (n =5/6; n =5/7) were patent and not relevantly stenosed (peak systolic velocity: EC grafts=76cms−1 ±4; DC grafts=77cms−1 ±5). Simulated haemodialysis punctures revealed significantly shorter bleeding times in all bioartificial grafts than in native jugular veins (P >0.001). Comparing native carotid arteries with DC grafts prior to and post-implantation, the latter differed significantly with respect to C (P >0.001; P =0.005), whereas only pre-implant DC grafts differed regarding BP (P =0.002); no differences were observed for SRT. Histology revealed complete endothelial surface coverage of EC, but not DC grafts. Furthermore, DC grafts exhibited areas of pronounced tissue calcification. Conclusion: The preclinical development of a bioartificial haemodialysis access graft with promising mechanical and morphological properties in a sheep model is feasible. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) exceeds infection and cancer as the leading cause of death. In the USA alone, approximately a million individuals suffer an acute myocardial infarction (AMI) annually. As the prevalence of CVD risk factors (e.g. hypertension, obesity and type 2 diabetes) rises, CVD is increasing in younger individuals. Fortunately, existing therapies have improved post-AMI mortality, but in turn have increased the prevalence of post-AMI heart failure (HF). Approximately half-a-million new HF cases are diagnosed each year in the USA. In the next 25 years, up to 15% of the population over the age of 65 in the USA is projected to have HF. Therapeutic interventions that prevent/reverse atherosclerosis, prevent post-AMI HF and halt the progressive functional deterioration once HF occurs are all needed. Cell therapy – either via exogenous delivery or by endogenous mobilization of cells – may be able to do so, in part, by improving the body’s capacity for repair. To date, primarily bone marrow- or blood-derived cells have been utilized after AMI to prevent left ventricular dysfunction, and skeletal myoblasts have been transplanted into failing myocardium. Preclinical studies are directed at prevention/reversal of atherosclerosis with bone marrow precursors, and ultimately at replacing failing heart with a cell-based bioartificial construct. [ABSTRACT FROM AUTHOR]

The article offers information on extracorporeal therapy. It states that this kind of therapy has expanded over the past years from solely artificial renal replacement therapy. It also forwards that it is crucial to provide multiple organ support therapy to patients with multiple organ dysfunction syndrome. Nanotechnology has also changed the way therapy is delivered to patients with kidney ailments.

Abstract: Bioartificial polymeric materials based on blends of dextran and poly(vinyl alcohol-co-acrylic acid) P(VA-co-AA) were prepared in the form of films and characterised to evaluate the miscibility of the natural component with the synthetic one. The idea of this work was to compatibilise PVA and dextran by introducing carboxylic groups along the PVA chains. The copolymer was synthesised and characterised in our laboratories. The results evidenced that the copolymer had an appropriate molecular weight and the content of PAA in the copolymer was 45% (weight). Then, films with different composition ratios were prepared by solution casting and analysed by differential scanning calorimetry (DSC), scanning electron microscopy (SEM), infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), chemical imaging analysis and mechanical tests. The results obtained indicated that the introduction of carboxylic groups along the PVA chains had a positive effect on the miscibility degree of the synthetic component with the biological one. [Copyright &y& Elsevier]

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Microbeads and microcapsules, employed for the microencapsulation of bioactive material, should provide sufficient mechanical protection to the encapsulated material, insure an optimal diffusion of desired molecules and, for transplantation-related applications, block the ingress of the imunoagents. Microcapsules are also often required to be smooth, spherical, within narrow size and membrane thickness distributions. In addition, the bioactive material has to be centred within the capsule, whose size should be minimized in relation to the bioactive material in order to optimise the diffusion of active molecules. The production process of such microcapsules should respect the aforementioned constraints and, in addition, be sterile, repeatable, robust, and harmless to the bioactive material while showing a high output. Two prototypes, dedicated to the microencapsulation of bioactive materials are presented. A semi-manual device permits the control of microcapsule properties for small scale (< 10 000 microcapsules), sterile production. An 'automated reaction control' system has also been developed. The features of the former are demonstrated for the repeatable production of 400 μm-microcapsules using the alginate/cellulose sulphate/poly(methylene-co-guanidine) system. The production rate is 500 000 microcapsules/h, with a size distribution within ±10% and membrane thickness distribution within ±5 μm. The latter in particular is, to the authors' knowledge, better than can be achieved with currently disclosed technologies, and is due to the precise control of the reaction conditions and time. [ABSTRACT FROM AUTHOR]

Acute hepatic failure is a rare clinical syndrome associated with high mortality. Hepatic failure leads to a well-recognised pattern of clinical signs and symptoms, sometimes with rapid deterioration and progression to multi-organ failure. Early recognition of this syndrome is essential for appropriate treatment; once identified, patients benefit from early interventional support and treatment in the intensive care unit. Aggressive management may allow stabilisation of patients before their transfer to specialist liver units. At present, orthotopic liver transplantation is the only treatment modality that provides significant improvement in outcome. This review examines the aetiology and clinical presentation of acute hepatic failure, providing guidelines regarding patient management. We present a critical appraisal of specific clinical areas, including the management of cardiovascular, cerebral, renal, coagulopathic and infective complications. Liver transplantation is discussed as well as emerging therapies including non-biological and hybrid liver support systems that may provide a "bridge to transplantation". [ABSTRACT FROM AUTHOR]

It is very likely that the need for bone substitutes will increase in the next decade. The present substitutes are generally bioactive and osteoconductive. Glassy or ceramic materials have been used up to now to act as a guide for bone healing tissue and were shown to admit bone apposition at their surface, probably due to the epitaxial growth of carbonated apatite crystals on it. Different forms of bone substitutes have been developed which do not show exactly the same properties. The reaction of bone tissue against bioactive material debris shows major differences from that of polymers or metals. In vitro models were developed to study the interface between bone cells and extracellular matrix, and the surface of bioactive material. Biotechnology makes available some morphogenetic proteins or growth factors in large quantities for combination with osteoconductive material which then can become osteoinductive. Bioartificial bone tissue constituted by a primary osteogenic cell line immobilised at the surface of osteoconductive materials made it possible to obtain osteogenic materials. The ideal bone biomaterial is still to be engineered. The combination of material sciences and molecular biology will help to optimise the next generation of material surfaces. [ABSTRACT FROM AUTHOR]