Tissue Replacement Research Articles

Protein‐Engineered Elastin Fibers as Building Blocks for The Textile‐Based Assembly of Tissue Equivalents

AbstractNative tissues feature unique hierarchical designs, in which fiber units are arranged from the bottom up in anisotropic patterns. The processing of biomaterials into fibers, followed by their textile‐like assembly into complex patterns, is therefore a promising avenue to engineer native‐like tissue replacements. Here it is shown for the first time the fabrication of meter‐long hydrogel fibers prepared from engineered elastin using a microinjection system and exploiting the catalyst‐free click chemistry. Given their similarity to native elastin, the fabricated elastin‐like fibers achieved excellent stretching (500%) and recoiling performance. Moreover, the fabrication scheme is compatible with the implementation of a salt‐leaching gas‐foaming approach, resulting in highly porous elastin‐like fibers (the first of their kind). From the translation perspective, the fibers can be autoclaved, which allows for sterilization and long‐term storage. Human umbilical vein endothelial cells cultured on autoclaved fibers produced a confluent endothelial layer lining the fiber surface, in which the cells became aligned in response to physiological fiber stretching. It is also shown that these functional fibers can be assembled by weaving, braiding and knitting, with various spatial patterns. Overall, the elastin‐like fibers can be used as building blocks for the reconstruction of functional tissues using the principles of textile technology.

Enhancing regenerative medicine: the crucial role of stem cell therapy.

Stem cells offer new therapeutic avenues for the repair and replacement of damaged tissues and organs owing to their self-renewal and multipotent differentiation capabilities. In this paper, we conduct a systematic review of the characteristics of various types of stem cells and offer insights into their potential applications in both cellular and cell-free therapies. In addition, we provide a comprehensive summary of the technical routes of stem cell therapy and discuss in detail current challenges, including safety issues and differentiation control. Although some issues remain, stem cell therapy demonstrates excellent potential in the field of regenerative medicine and provides novel tactics and methodologies for managing a wider spectrum of illnesses and traumas.

A study of mechanical and magnetic properties in a metastable Zr–10Nb–6Sn alloy for MRI-compatible hard tissue replacements

In this study, we presented an investigation into a newly developed metastable Zr–10Nb–6Sn alloy meticulously tailored to fulfill the demanding requisites of magnetic resonance imaging (MRI)-compatible hard implants. The effect of cold rolling reduction (0%, 10%, 20% and 40%) on the mechanical properties and magnetic susceptibility of the alloy has been systematically studied. With the increase of cold rolling reduction, the yield strength and tensile strength of the alloy increase, while the elastic modulus decreases first and then increases slightly. The sample with 40% cold rolling (CR40%) exhibits excellent matching of yield strength ∼ 905 MPa and elastic modulus ∼55.8 GPa, with a superior yield strength-to-elastic modulus ratio than that of other reported metallic biomedical materials. The deformation mechanism of Zr–10Nb–6Sn alloy during cold rolling includes stress-induced α" phase, kink bands and dislocation slip. Due to the addition of Sn element with low magnetic susceptibility (0.03× 10−6 cm3g−1) and the formation of ω phase, the solution-treated sample (CR0%) has a low magnetic susceptibility ∼ 0.77 × 10−6 cm3g−1, which is significantly lower than that of other reported titanium and zirconium based biomedical alloys. The magnetic susceptibility of the samples increases from 0.77× 10−6 cm3g−1 to 1.35 × 10−6 cm3g−1 as the cold rolling reduction increases, which may be attributed to the decrease in ω-phase content and the increase in α''-phase content during cold rolling. Hence, the cold-workable Zr–10Nb–6Sn alloy, exhibiting exceptional mechanical compatibility and low magnetic susceptibility, holds promise as a potential alloy for MRI-compatible hard tissue replacements.

Investigation of Mechanical Properties of Ti6Al4V Alloy Foams produced by Powder Metallurgy Method

In this study, it was aimed to production titanium alloy implants, which are widely used in the biomedical industry, as foamed materials under different mechanical alloying and sintering conditions using the powder metallurgy method Tİ6Al4V alloy is good mechanical properties, good biocompatibility properties and good corrosion resistance used as hard tissue replacements and implants. Similar mechanic properties with bone are expected from the implant to work coherently for long cycles of use and without any failure. Especially, elastic modulus of implant must be similar with bones, if not, some damages at bone surface and fallowing repeats of implant surgeries are reported. This situation has a destructive effect on health, finance, and comfort of the patient/user of the implant. In this study, powder metallurgy and space holder removal methods were used to produce porous Ti6Al4V specimens. Throughout the project study different space holder materials and binder agents were used. As weight percent, 20%, 30%, 40%, 60%, 70%, 80% porous specimens were pressed at uniaxial press machine, and sintered to the 850 ºC at argon atmosphere in furnace to reduce the oxidation to the level as low as possible. The E-Modulus values of the specimens reached the desired values with increasing porosity. It was obtained as 88 MPa in the specimen with 80% porosity, decreasing inversely proportionally, especially from the 60% porosity rate.

High-throughput sequencing and characterization of potentially pathogenic fungi from the vaginal mycobiome of giant panda (Ailuropoda melanoleuca) in estrus and non-estrus.

The giant panda (Ailuropoda melanoleuca) reproduction is of worldwide attention, and the vaginal microbiome is one of the most important factors affecting the reproductive rate of giant pandas. The aim of this study is to investigate the diversity of vaginal mycobiota structure, and potential pathogenic fungi in female giant pandas during estrus and non-estrus. This study combined with high-throughput sequencing and laboratory testing to compare the diversity of the vaginal mycobiota in giant pandas during estrus and non-estrus, and to investigate the presence of potentially pathogenic fungi. Potentially pathogenic fungi were studied in mice to explore their pathogenicity. The results revealed that during estrus, the vaginal secretions of giant pandas play a crucial role in fungal colonization. Moreover, the diversity of the vaginal mycobiota is reduced and specificity is enhanced. The abundance of Trichosporon and Cutaneotrichosporon in the vaginal mycobiota of giant pandas during estrus was significantly higher than that during non-estrus periods. Apiotrichum and Cutaneotrichosporon were considered the most important genera, and they primarily originate from the environment owing to marking behavior exhibited during the estrous period of giant pandas. Trichosporon is considered a resident mycobiota of the vagina and is an important pathogen that causes infection when immune system is suppressed. Potentially pathogenic fungi were further isolated and identified from the vaginal secretions of giant pandas during estrus, and seven strains of Apiotrichum (A. brassicae), one strain of Cutaneotrichosporon (C. moniliiforme), and nine strains of Trichosporon (two strains of T. asteroides, one strain of T. inkin, one strain of T. insectorum, and five strains of T. japonicum) were identified. Pathogenicity results showed that T. asteroides was the most pathogenic strain, as it is associated with extensive connective tissue replacement and inflammatory cell infiltration in both liver and kidney tissues. The results of this study improve our understanding of the diversity of the vaginal fungi present in giant pandas and will significantly contribute to improving the reproductive health of giant pandas in the future.

Arrhythmogenic Cardiomyopathy: Definition, Classification and Arrhythmic Risk Stratification.

Arrhythmogenic cardiomyopathy (ACM) is a heart disease characterized by a fibrotic replacement of myocardial tissue and a consequent predisposition to ventricular arrhythmic events, especially in the young. Post-mortem studies and the subsequent diffusion of cardiac MRI have shown that left ventricular involvement in arrhythmogenic cardiomyopathy is common and often develops early. Regarding the arrhythmic risk stratification, the current scores underestimate the arrhythmic risk of patients with arrhythmogenic cardiomyopathy with left involvement. Indeed, the data on arrhythmic risk stratification in this group of patients are contradictory and not exhaustive, with the consequence of not correctly identifying patients at a high arrhythmic risk who deserve protection from arrhythmic death. We propose a literature review on arrhythmic risk stratification in patients with ACM and left involvement to identify the main features associated with an increased arrhythmic risk in this group of patients.

Our Experience in the Surgical Management of Arterio-Venous Malformations of the head and neck

Vascular anomalies comprise a diverse group of abnormalities in blood vessel morphogenesis that usually occur prenatally. Arterio-venous malformations (AVMs) are rare congenital vascular lesions accounting for 1.5% of all vascular anomalies, with 50% of them occur in the oral and maxillo-facial regions. Treatment of large, complex vascular lesions is a serious challenge for patients and surgeons because it can cause disfigurement and massive haemorrhage, which may be spontaneous or the result of surgical intervention. Our study aimed to demonstrate surgical management of massive AVMs of the head and neck. This retrospective study shows the treatment outcomes of 28 patients with massive maxillo-facial vascular malformations, who presented to our department for treatment from 1 January 2015 to 31 July 2022. Twenty-eight patients with a mean age of 17.32 ± 12.21 years (women: 15, men: 13) were enrolled in the study. Diagnosis included extra cranial AVMs of the head and neck region. Treatment modalities, in isolation or combination, included angioembolisation procedure, sclerotherapy, and surgery. Management of AVMs is challenging owing to the replacement of normal tissue by the diseased ones and the high rate of recurrence. Hence, multi-modal approaches are needed for the effective restoration of tissues.

In vitro study on the inflammatory response of chitosan nanoparticles as a potential siRNA carrier targeting towards osteosarcoma cells

Abstract There have been significant developments in the use of siRNA in the silencing of cancer-allied target proteins with substantial apoptotic effects. Nevertheless, the challenges regarding siRNA delivery for cancer therapy remain a major concern for taking these therapies successfully from laboratory to in vivo studies. Biomaterials are defined traditionally as any material that is used for either medical or dental applications that contact the host cells in any form, such as a drug carrier a device, or as a prosthesis towards the replacement of damaged tissues. The main issues to be fulfilled by the biomaterial for clinical applications are biocompatibility, bioactivity, ability to carry drug to target site, inflammatory responses and other factors based on its application. The present study focuses on the in vitro inflammatory response to the CS nanoparticles using RAW 264.7 and bone marrow derived macrophage cells. Additionally, the in vitro release kinetics of siRNA with varying concentrations and pH, transfection efficacy and biocompatibility were also investigated. The results of siRNA cumulative release increased at pH 5 and 3, which may be corresponding to the protonation, and a delayed release was seen at 7, which was ascribed to unprotonated amine groups inside the CS. The results of release kinetics confirmed a sustained release of siRNA from CS NPs. Considering that CS is a biocompatible polymer, it typically has little impact/damage on cells, as numerous researchers have observed during in vitro experiments. Inflammatory studies were carried out in vitro with RAW 264.7 and BMC cells derived from mice. The gene and protein expression studies showed that the materials might cause some slight inflammation on exposure with both RAW 264.7 and BMC cells in vitro, which is completely negligible. However, putting together the overall data it can be concluded that CS NPs can be a promising material for in vivo applications, which is in agreement with the results of other researchers, but the only concern being its ability to carry siRNA and protect it from nuclease and other enzymatic attacks.

A zirconia/tantalum biocermet: in vitro and in vivo evaluation for biomedical implant applications.

A biocermet made of zirconia/20 vol% tantalum (3Y-TZP/Ta) is a new composite with exceptional capabilities due to a combination of properties that are rarely achieved in conventional materials (high strength and toughness, cyclic fatigue resistance and flaw tolerance, wear resistance, corrosion resistance, electrical conductivity, etc.). In this study, for the first time, the biomedical performance of a 3Y-TZP/Ta biocermet was evaluated in detail. Its in vitro biocompatibility was assessed using mesenchymal stem cell culture. The effectiveness of in vivo osteointegration of the biocermet was confirmed 6 months after implantation into the proximal tibiae of New Zealand white rabbits. In addition, the possibility of using magnetic resonance imaging (MRI) for medical analysis of the considered biocermet material was studied. The 3Y-TZP/Ta composite showed no injurious effect on cell morphology, extracellular matrix production or cell proliferation. Moreover, the implanted biocermet appeared to be capable of promoting bone growth without adverse reactions. On the other hand, this biocermet demonstrates artefact-free performance in MRI biomedical image analysis studies, making it more suitable for implant applications. These findings open up possibilities for a wide range of applications of these materials in orthopedics, dentistry and other areas such as replacement of hard tissues.

The role of natural rubber latex nanoparticles in tissue engineering

Natural rubber latex is derived from the lactiferous sap of the Hevea brasiliensis (para rubber tree) and has been used in traditional medicine due to its bioactive compounds. There are over 35,000 species of plants that produce latex. Recently, NRL has shown promise in tissue engineering for the replacement and regeneration of various tissues, such as skin, eardrums, bones, and dental alveoli. This presents a unique opportunity to repair or replace failing organs or tissues. This review highlights the current development of Natural rubber latex in tissue engineering, and identifies importance for investigation on cytotoxicity of Natural rubber latex nanoparticles. In addition, promising results regarding the current challenges and perspectives of Natural rubber latex-based tissue engineering is discussed.

Role of Hedgehog Signaling Pathways in Multipotent Mesenchymal Stem Cells Differentiation.

Multipotent mesenchymal stem cells (MSCs) have high self-renewal and multi-lineage differentiation potentials and low immunogenicity, so they have attracted much attention in the field of regenerative medicine and have a promising clinical application. MSCs originate from the mesoderm and can differentiate not only into osteoblasts, cartilage, adipocytes, and muscle cells but also into ectodermal and endodermal cell lineages across embryonic layers. To design cell therapy for replacement of damaged tissues, it is essential to understand the signaling pathways, which have a major impact on MSC differentiation, as this will help to integrate the signaling inputs to initiate a specific lineage. Hedgehog (Hh) signaling plays a vital role in the development of various tissues and organs in the embryo. As a morphogen, Hh not only regulates the survival and proliferation of tissue progenitor and stem populations but also is a critical moderator of MSC differentiation, involving tri-lineage and across embryonic layer differentiation of MSCs. This review summarizes the role of Hh signaling pathway in the differentiation of MSCs to mesodermal, endodermal, and ectodermal cells.

A Multicenter Pilot Study of a Novel Allograft Adipose Matrix in Malar and Prejowl Volume Restoration.

Allograft adipose matrix (AAM) offers a novel, off-the-shelf, and readily available natural option in the treatment of facial soft tissue volume and reconstructive deficits. AAM is a natural soft tissue supplement or replacement that can support cushioning and volume correction. A prospective multicenter pilot study evaluated AAM in facial volume restoration. Eleven women (mean age of 55.8 ± 10.9 y) with midface volume deficit were followed up for 24 weeks after AAM treatment in this institutional review board-approved multicenter pilot study. The clinical safety and efficacy of the AAM treatment were evaluated using clinical scales and three-dimensional quantitative facial photography. AAM was safe to address facial volume deficits, with minor site-related adverse events and discomfort that resolved within 2-4 weeks. Observations also revealed facial volume improvements throughout the study with 91% positive responders. At week 24, the subject facial satisfaction scores revealed an 86% increase compared to baseline, along with a statistically significantly improved midface fullness compared to baseline. AAM offers a natural and safe option for midface volume restoration and supports overall satisfaction and volume improvements.

Polyimide as a biomedical material: advantages and applications.

Polyimides (PIs) are a class of polymers characterized by strong covalent bonds, which offer the advantages of high thermal weight, low weight, good electronic properties and superior mechanical properties. They have been successfully used in the fields of microelectronics, aerospace engineering, nanomaterials, lasers, energy storage and painting. Their biomedical applications have attracted extensive attention, and they have been explored for use as an implantable, detectable, and antibacterial material in recent years. This article summarizes the progress of PI in terms of three aspects: synthesis, properties, and application. First, the synthetic strategies of PI are summarized. Next, the properties of PI as a biological or medical material are analyzed. Finally, the applications of PI in electrodes, biosensors, drug delivery systems, bone tissue replacements, face masks or respirators, and antibacterial materials are discussed. This review provides a comprehensive understanding of the latest progress in PI, thereby providing a basis for developing new potentially promising materials for medical applications.

Hidroxiapatita sustituida con estroncio: plataforma para regeneración ósea con actividad antimicrobiana

Hydroxyapatite (HA) is a calcium phosphate with great analogy to biological apatite. Because of that it has demonstrated excellent results in clinical applications for bone tissue replacement. However, there are certain pathologies such as osteopenia or osteoporosis where the natural bone formation capacity is diminished and which may require an extra stimulus to accelerate and guarantee the osseointegration processes. In these cases, doping hydroxyapatite with strontium ions (Sr-HA) has given excellent results. This ion participates in bone metabolism in various ways and, while stimulating osteosynthesis, it inhibits osteoclast to a certain extent, which as a whole promotes the formation of new bone more quickly. Thus, the development of Sr-HA implants has evolved to not only consider substitutes for bone tissue with greater speed of osseointegration, but also to become platforms for the release of other active ingredients that can also counteract different medical conditions. This work delves into the complexity of septic processes associated with prostheses, which justifies the diversity of approaches to this clinical problem from biomedical engineering. In addition, review different formulations based on Sr-HA reported to eradicate septic processes. In particular, it explores new devices carrying antibiotics (Antb/Sr-HA) and new platforms that have been formed from the double ion doping of the HA where one of those ions is strontium and the other is some metallic element with demonstrated antibacterial activity (M/Sr-HA).

The Effect of Pore Length on The Mechanical Properties of Vascular Scaffold Due to Systolic Pressure

Tissue replacements are highly limited due to the lack of vascularized tissue in the engineered tissue. Thus, incorporating the vascular scaffold in any injured tissue or organ is critical in the tissue regeneration. As one of elastic tissue in human body, mechanical properties are vital in engineering a vascular scaffold. Besides, interconnected pores and scaffold porosity are among the main considerations in designing the scaffold for allowing the vascularization. Therefore, this study aims to simulate the mechanical properties of three-dimensional (3D) printed vascular scaffold by observing the deformation and elasticity after being applied with the maximum systolic pressure. Scaffolds with three different pore lengths were simulated for compression and tensile analysis by using Finite Element Analysis (FEA) based on polyethylene terephthalate (PET) material’s properties. The findings indicated that effective elastic modulus of the vascular scaffolds varied based on the pore length with shortest pore length gave the highest elasticity, whilst scaffold with the longest pore length gave lowest elasticity. Besides, stress value of compression and tensile analysis for all scaffolds were did not exceed the PET’s yield strength that indicated the designed scaffolds will have high potential for vascular tissue engineering applications.

Bioactive layered double hydroxide nanoparticles loaded calcein under GelMA scaffolds promoted osteogenesis and angiogenesis for bone regeneration

In regenerative medicine and tissue engineering, the repair and replacement of damaged or lost bone tissue remains an enduring challenge. Traditional approaches often fail to achieve desired outcomes, but recent advancements in material science have introduced innovative solutions to this issue. Gelatin methacryloyl (GelMA), which is derived from gelatin, has a unique combination of biocompatibility and tunable physical properties for bone tissue engineering applications. In this study, a novel composite was constructed to combine the characteristics of GelMA and bioactive layered double hydroxide (LDH) loaded calcein. The GelMA-LDH-calcein (GLC) scaffold is designed to promote the osteogenic differentiation of mesenchymal stem cells (MSCs) and provide a microenvironment conducive to osteogenic differentiation, ultimately increasing the osteogenic activity to support bone regeneration. Our data demonstrated that GLC promoted the osteogenic differentiation related gene (ALP, Runx2, and OPG) expression in bone marrow-derived MSCs (BMSCs) and angiogenesis of human vascular epithelial cells (HUVECs), making it particularly valuable in the application of bone regeneration in vivo. Through the design, synthesis, and optimization of GLC composites, the optimized scaffolds can provide structure supporting and biological activity for cell proliferation, which promoted bone defect regeneration and could be used for further clinical applications.

Fatigue and fracture of soft collagenous tissues mineralized in vitro

Biomineralization occurs in natural organisms, such as bones, teeth, shells and tendons. The formation mechanism and mechanical properties have been extensively studied for mineralized hard tissues, especially for bone and teeth. However, the research on the evolution of mechanical properties for mineralized soft tissues remains challenging due to the long period of mineralization. Here we use polymer-induced liquid-precursor (PILP) method to achieve accelerated in vitro mineralization of bovine pericardium with SrCO3. The modulus, tensile strength, toughness, and suture retention force of mineralized tissues have been characterized. After 30 days of mineralization, both the tensile strength and toughness decrease by two orders of magnitude. We carry out cyclic suture retention test to characterize the fatigue properties of mineralized tissues, and find that the cycle to failure of mineralized tissues is 10-100 times lower than that of unmineralized tissues. The degradation of mechanical properties results from the microstructure change of mineralized tissues, where collagen fibers change from curled to straight configuration. After mineralization, the interfibrous slippage is limited, and the fracture mode changes from fiber pullout to fiber break. Finite element analysis has been carried out to simulate the fracture and suture retention properties, and the simulation can well reproduce experimental results. The study may provide insights for tissue replacement and repairing.

Comparative Analysis of Various Spider Silks in Regard to Nerve Regeneration: Material Properties and Schwann Cell Response.

Peripheral nerve reconstruction through the employment of nerve guidance conduits with Trichonephila dragline silk as a luminal filling has emerged as an outstanding preclinical alternative to avoid nerve autografts. Yet, it remains unknown whether the outcome is similar for silk fibers harvested from other spider species. This study compares the regenerative potential of dragline silk from two orb-weaving spiders, Trichonephila inaurata and Nuctenea umbratica, as well as the silk of the jumping spider Phidippus regius. Proliferation, migration, and transcriptomic state of Schwann cells seeded on these silks are investigated. In addition, fiber morphology, primary protein structure, and mechanical properties are studied. The results demonstrate that the increased velocity of Schwann cells on Phidippus regius fibers can be primarily attributed to the interplay between the silk's primary protein structure and its mechanical properties. Furthermore, the capacity of silk fibers to trigger cells toward a gene expression profile of a myelinating Schwann cell phenotype is shown. The findings for the first time allow an in-depth comparison of the specific cellular response to various native spider silks and a correlation with the fibers' material properties. This knowledge is essential to open up possibilities for targeted manufacturing of synthetic nervous tissue replacement.

Experimental analysis and biaxial biomechanical behaviour of ex-vivo sheep trachea

Besides surgery, there are currently no other established methods for routine treatment of tracheal pathologies such a tracheal stenosis or tracheal and airway tumors. Even with several attempts to repair the infected trachea with artificial and natural prostheses, there is a need for the fundamental understanding of the tissue’s mechanical behaviour. The purpose of this study was to investigate the mechanical behaviour of the tracheal tissue under biaxial tensile loading. Furthermore, the study examines the material properties of the tissue through a study of the model parameters for six constitutive models. Materials and methods: The fourteen (n = 14) specimens of sheep trachea (Vleis Merino) measured to be ∼30 × 20 mm where only the effective area of ∼25 × 16 mm was subjected to engineering strain. In this study, we assume that the tracheal tissue is anisotropic and incom-pressible, therefore we apply and study the material parameters from six different constitutive material models. Results: The results show that the tracheal tissue is twice as stiff along the circumferential direction as it is along the longitudinal direction. It is also observed that the material properties are different (non-homogeneous) along the trachea. Conclusion: The findings of this study will benefit computational models for the study of tracheal diseases or injuries. Furthermore, these findings will assist in the development of regenerative medicine for different tracheal pathologies and in the bioengineering of replacement tissue in cases of damage.

Arrhythmogenic Right Ventricular Dysplasia Presenting with Sustained Ventricular Tachycardia: A Case Report

Arrhythmogenic right ventricular dysplasia (ARVD) is a cardiomyopathy characterized pathologically by fibrofatty tissue replacement of the myocyte of the right ventricle (RV) and clinically by life-threatening ventricular arrhythmias in young people. It is a major cause of sudden death. We present the case of a 60-year-old man with cardiovascular risk factors, was admitted for unstable ventricular tachycardia (VT) treated immediately with synchronized cardioversion. After the stabilization of the patient, Electrocardiogram demonstrated an epsilon wave in precordial leads and diffuse T-wave inversions. Transthoracic echocardiography revealed a dilated, hypokinetic right ventricle with moderately reduced function and a focal area of dyskinesia. The diagnosis of arrhythmogenic right ventricular dysplasia (ARVD) was made and an implantable cardioverter defibrillator (ICD) was indicated for secondary prevention. This case report will present the clinical presentation, diagnosis and management of this rare disease.