Aspects Of Tissue Engineering Research Articles

Emerging approaches for the development of artificial islets

AbstractThe islet of Langerhans, functioning as a “mini organ”, plays a vital role in regulating endocrine activities due to its intricate structure. Dysfunction in these islets is closely associated with the development of diabetes mellitus (DM). To offer valuable insights for DM research and treatment, various approaches have been proposed to create artificial islets or islet organoids with high similarity to natural islets, under the collaborative effort of biologists, clinical physicians, and biomedical engineers. This review investigates the design and fabrication of artificial islets considering both biological and tissue engineering aspects. It begins by examining the natural structures and functions of native islets and proceeds to analyze the protocols for generating islets from stem cells. The review also outlines various techniques used in crafting artificial islets, with a specific focus on hydrogel‐based ones. Additionally, it provides a concise overview of the materials and devices employed in the clinical applications of artificial islets. Throughout, the primary goal is to develop artificial islets, thereby bridging the realms of developmental biology, clinical medicine, and tissue engineering.

Recent advances in the development of bioartificial pancreas using 3D bioprinting for the treatment of type 1 diabetes: a review

Type 1 diabetes is a chronic condition that results from the destruction of insulin-producing β-cells in the pancreas. Current treatments for type 1 diabetes, such as insulin therapy and pancreatic islet transplantation, have several limitations and, hence not quite effective in the long run. As current therapy methods fail to slow disease development, novel strategies such as the development of a bioartificial pancreas are being seriously considered. Over the last decade, research has focused on tissue engineering, which aids in the design of biological alternatives for the repair and replacement of non-functional or damaged organs. Three dimensional (3D) bioprinting technology which employs 3D printing technology to generate 3D tissue-like structures from biomaterials and cells, offers a promising solution for the treatment of type 1 diabetes by providing the ability to generate functional endocrine pancreatic tissue. Bioprinted structures are therefore an important aspect of tissue engineering because they have been found to replicate the native extracellular matrix, promoting cell survival and proliferation. In this review, recent developments in 3D bioprinting of endocrine pancreas for the treatment of type 1 diabetes particularly focussing on the choice of cells, biomaterials, growth factors, and essential considerations have been discussed in detail. Additionally, the key challenges and perspectives towards recapitulation of the pancreatic function of the pancreatic organ engineering technologies have also been discussed.

Optimization of Polyvinyl Alcohol-Based Electrospun Fibers with Bioactive or Electroconductive Phases for Tissue-Engineered Scaffolds

The accurate mimicking of the fibrillary structure of the extracellular matrix represents one of the critical aspects of tissue engineering, playing a significant role in cell behavior and functions during the regenerative process. This work proposed the design of PVA-based multi-component membranes as a valuable and highly versatile strategy to support in vitro regeneration of different tissues. PVA can be successfully processed through electrospinning processes, allowing for the integration of other organic/inorganic materials suitable to confer additive bio-functional properties to the fibers to improve their biological response. It was demonstrated that adding polyethylene oxide (PEO) improves fiber processability; moreover, SEM analyses confirmed that blending PVA with PEO or gelatin enables the reduction of fiber size from 1.527 ± 0.66 μm to 0.880 ± 0.30 μm and 0.938 ± 0.245 μm, respectively, also minimizing defect formation. Furthermore, in vitro tests confirmed that gelatin integration allows the formation of bioactive nanofibers with improved biological response in terms of L929 adhesion and proliferation. Lastly, the processability of PVA fibers with conductive phases such as polyvinylpyrrolidone (PVP) or poly(3,4-ethylene dioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) has also been verified. From this perspective, they could be promisingly used to design electroactive composite fibers able to support the regeneration process of electrically stimulated tissues such as nerves or muscles.

Effect of Flow Rate Modulation on Alginate Emulsification in Multistage Microfluidics.

The encapsulation of stem cells into alginate microspheres is an important aspect of tissue engineering or bioprinting which ensures cell growth and development. We previously demonstrated the encapsulation of stem cells using the hanging drop method. However, this conventional process takes a relatively long time and only produces a small-volume droplet. Here, an experimental approach for alginate emulsification in multistage microfluidics is reported. By using the microfluidic method, the emulsification of alginate in oil can be manipulated by tuning the flow rate for both phases. Two-step droplet emulsification is conducted in a series of polycarbonate and polydimethylsiloxane microfluidic chips. Multistage emulsification of alginate for stem cell encapsulation has been successfully reported in this study under certain flow rates. Fundamental non-dimensional numbers such as Reynolds and capillary are used to evaluate the effect of flow rate on the emulsification process. Reynolds numbers of around 0.5-2.5 for alginate/water and 0.05-0.2 for oil phases were generated in the current study. The capillary number had a maximum value of 0.018 to ensure the formation of plug flow. By using the multistage emulsification system, the flow rates of each process can be tuned independently, offering a wider range of droplet sizes that can be produced. A final droplet size of 500-1000 µm can be produced using flow rates of 0.1-0.5 mL/h and 0.7-2.4 mL/h for the first stage and second stage, respectively.

Biodegradable natural and synthetic polymers for the development of electrospun nanofibrous scaffolds for various tissue engineering applications

Following a tissue injury/ damage, the regeneration of cells at the affected area is very critical. Fewer cell types like dermal cells are capable of cellular division to a smaller extent. But following more significant cellular damage, there comes an urgent need to replace these defective cells or tissues, where most traditional approaches of medicinal treatments fail. Tissue engineering offers an alternative solution that is more ideal under these circumstances. It is an interdisciplinary field of science that tries to integrate life science into engineering principles with the purpose of replacing damaged cells/tissues. In addition, the overall process of tissue growth and differentiation in vivo requires the presence of various growth factors at the nano-sized range. The current trend is to encompass nanotechnology along with tissue engineering aspects. Scaffolds being the most important component of tissue engineering application, the electrospinning process is used to generate nanofibrous scaffolds. Electrospinning makes use of different natural and synthetic polymers. These polymers can provide structural support upon which cellular growth occurs and hence these polymers are suitable for various biomedical applications. This review study attempts to cover the basics of the electrospinning process, different natural and synthetic polymers and their significant biomedical applications.

De novo testicular tissue generation from non-testicular cell lines, biologic and synthetic scaffolds: Current findings and future translational applications.

In recent decades, reproductive science has revolutionized the options for biological parenthood for the 20-50% of infertility cases affected by male factors. However, current solutions exclude those who are infertile due to absent testicular tissue. This includes anorchic 46, XY individuals due to trauma or congenital factors and transgender men with a 46, XX genotype. There is a clinical need for methods to restore testicular function independent of pre-existing testicular tissue. This mini-review analyzes studies that have applied non-testicular cell lines to generate germline and non-germline testicular parenchymal components. While only 46, XY cell lines have been evaluated in this context to date, the potential for future application of cell lines from 46, XX individuals is also included. Additionally, the role of varied culture methods, media supplementation, and biologic and synthetic scaffolds to further support testicular parenchyma generation are critiqued. De novo testicular tissue generation in this manner will require a focus on both cellular and environmental aspects of tissue engineering. Put together, these studies highlight the future potential for expanded clinical, reproductive, and endocrine management options for individuals who are currently excluded from aspects of biologic reproduction most consistent with their gender identity and reproductive preferences.

Magnetism in Dentistry: Review and Future Perspectives

Tissue engineering or tissue reconstruction/repair/regeneration may be considered as a guiding strategy in oral and maxillofacial surgery, as well as in endodontics, orthodontics, periodontics, and daily clinical practice. A wide range of techniques has been developed over the past years, from tissue grafts to the more recent and innovative regenerative procedures. Continuous research in the field of natural and artificial materials and biomaterials, as well as in advanced scaffold design strategies has been carried out. The focus has also been on various growth factors involved in dental tissue repair or reconstruction. Benefiting from the recent literature, this review paper illustrates current innovative strategies and technological approaches in oral and maxillofacial tissue engineering, trying to offer some information regarding the available scientific data and practical applications. After introducing tissue engineering aspects, an overview on additive manufacturing technologies will be provided, with a focus on the applications of superparamagnetic iron oxide nanoparticles in the biomedical field. The potential applications of magnetic fields and magnetic devices on the acceleration of orthodontic tooth movement will be analysed.

PoreScript: Semi-automated pore size algorithm for scaffold characterization

The scaffold pore size influences many critical physical aspects of tissue engineering, including tissue infiltration, biodegradation rate, and mechanical properties. Manual measurements of pore sizes from scanning electron micrographs using ImageJ/FIJI are commonly used to characterize scaffolds, but these methods are both time-consuming and subject to user bias. Current semi-automated analysis tools are limited by a lack of accessibility or limited sample size in their verification process. The work here describes the development of a new MATLAB algorithm, PoreScript, to address these limitations. The algorithm was verified using three common scaffold fabrication methods (e.g., salt leaching, gas foaming, emulsion templating) with varying pore sizes and shapes to demonstrate the versatility of this new tool. Our results demonstrate that the pore size characterization using PoreScript is comparable to manual pore size measurements. The PoreScript algorithm was further evaluated to determine the effect of user-input and image parameters (relative image magnification, pixel intensity threshold, and pore structure). Overall, this work validates the accuracy of the PoreScript algorithm across several fabrication methods and provides user-guidance for semi-automated image analysis and increased throughput of scaffold characterization.

Guiding cell adhesion and motility by modulating cross-linking and topographic properties of microgel arrays.

Biomaterial-driven modulation of cell adhesion and migration is a challenging aspect of tissue engineering. Here, we investigated the impact of surface-bound microgel arrays with variable geometry and adjustable cross-linking properties on cell adhesion and migration. We show that cell migration is inversely correlated with microgel array spacing, whereas directionality increases as array spacing increases. Focal adhesion dynamics is also modulated by microgel topography resulting in less dynamic focal adhesions on surface-bound microgels. Microgels also modulate the motility and adhesion of Sertoli cells used as a model for cell migration and adhesion. Both focal adhesion dynamics and speed are reduced on microgels. Interestingly, Gas2L1, a component of the cytoskeleton that mediates the interaction between microtubules and microfilaments, is dispensable for the regulation of cell adhesion and migration on microgels. Finally, increasing microgel cross-linking causes a clear reduction of focal adhesion turnover in Sertoli cells. These findings not only show that spacing and rigidity of surface-grafted microgels arrays can be effectively used to modulate cell adhesion and motility of diverse cellular systems, but they also form the basis for future developments in the fields of medicine and tissue engineering.

Interactions between cells and biomaterials in tissue engineering: a review

Seed cells, biomaterials and growth factors are three important aspects in tissue engineering. Biomaterials mimic extra cellular matrix in vivo, providing a sound environment for cells to grow and attach, so as to maintain cell viability and function. The physicochemical properties and modification molecules of material surface mediate cell behaviors like cell adhesion, proliferation, migration and differentiation, which in turn affect cellular function and tissue regeneration efficacy. Furthermore, the modification molecules of material surface are the direct contact point for cell adhesion and growth. Therefore, the interactions between cells and surface modification molecules are the key to tissue engineering. This review summarizes the effects of surface modification molecules on cell phenotypes and functions.

HYDRO-GEL POLYMERS AND 3D BIOPRINTING IN SKIN ENGINEERING - A REVIEW

Tissue engineering is a booming field of science and technology. The sheer potential it emanates is enough to place all attention on it. Tissue engineering is widely researched for the development of skin substitutes to treat patients with infections or disorders. Commercial skin substitutes provide a promising future to medicine. The availability of different biomaterials for the production of artificial skin has posed many questions regarding the feasibility, usability, and practicality of these products. The articles reviewed discuss tissue engineering as a challenging field and how skin substitutes are vital. Biomaterials and hydrogel studies are found to be a game changer for the field. The functional aspects have been discussed with the physical characteristics for better understanding. Different techniques of printing biological structures by using scaffolds are discussed in detail. Scaffolds provide a very efficient structural composition for the bioprinter to manifest the organ to be printed. Bioink composition and preparation with scientific knowledge make it a very important asset in tissue engineering. The future of regenerative medicine and organ transplantation is expected to be safe within the various aspects of tissue engineering. The vast possibilities it offers is hard to not explore further. Even though the research field has come a long way since the beginning of tissue culture in the 1970s, there are still different challenges to be faced and conquered.

Cardiac Organoids to Model and Heal Heart Failure and Cardiomyopathies.

Cardiac tissue engineering aims at creating contractile structures that can optimally reproduce the features of human cardiac tissue. These constructs are becoming valuable tools to model some of the cardiac functions, to set preclinical platforms for drug testing, or to alternatively be used as therapies for cardiac repair approaches. Most of the recent developments in cardiac tissue engineering have been made possible by important advances regarding the efficient generation of cardiac cells from pluripotent stem cells and the use of novel biomaterials and microfabrication methods. Different combinations of cells, biomaterials, scaffolds, and geometries are however possible, which results in different types of structures with gradual complexities and abilities to mimic the native cardiac tissue. Here, we intend to cover key aspects of tissue engineering applied to cardiology and the consequent development of cardiac organoids. This review presents various facets of the construction of human cardiac 3D constructs, from the choice of the components to their patterning, the final geometry of generated tissues, and the subsequent readouts and applications to model and treat cardiac diseases.

2D Nanomaterials for Tissue Engineering and Regenerative Nanomedicines: Recent Advances and Future Challenges.

Regenerative medicine has become one of the hottest research topics in medical science that provides a promising way for repairing tissue defects in the human body. Due to their excellent physicochemical properties, the application of 2D nanomaterials in regenerative medicine has gradually developed and has been attracting a wide range of research interests in recent years. In particular, graphene and its derivatives, black phosphorus, and transition metal dichalcogenides are applied in all the aspects of tissue engineering to replace or restore tissues. This review focuses on the latest advances in the application of 2D-nanomaterial-based hydrogels, nanosheets, or scaffolds that are engineered to repair skin, bone, and cartilage tissues. Reviews on other applications, including cardiac muscle regeneration, skeletal muscle repair, nerve regeneration, brain disease treatment, and spinal cord healing are also provided. The challenges and prospects of applications of 2D nanomaterials in regenerative medicine are discussed.

The Role of Collagen-Based Biomaterials in Chronic Wound Healing and Sports Medicine Applications.

Advancements in tissue engineering have taken aim at treating tissue types that have difficulty healing naturally. In order to achieve improved healing conditions, the balance of exogenous matrix, cells, and different factors must be carefully controlled. This review seeks to explore the aspects of tissue engineering in specific tissue types treated in sports medicine and advanced wound management from the perspective of the matrix component. While the predominant material to be discussed is collagen I, it would be remiss not to mention its relation to the other contributing factors to tissue engineered healing. The main categories of materials summarized here are (1) reconstituted collagen scaffolds, (2) decellularized matrix tissue, and (3) non-decellularized tissue. These three groups are ordered by their increase in additional components beyond simply collagen.

Hierarchical fibrous guiding cues at different scales influence linear neurite extension

Surface topographies at micro- and nanoscales can influence different cellular behavior, such as their growth rate and directionality. While different techniques have been established to fabricate 2-dimensional flat substrates with nano- and microscale topographies, most of them are prone to high costs and long preparation times. The 2.5-dimensional fiber platform presented here provides knowledge on the effect of the combination of fiber alignment, inter-fiber distance (IFD), and fiber surface topography on contact guidance to direct neurite behavior from dorsal root ganglia (DRGs) or dissociated primary neurons. For the first time, the interplay of the micro-/nanoscale topography and IFD is studied to induce linear nerve growth, while controlling branching. The results demonstrate that grooved fibers promote a higher percentage of aligned neurite extension, compensating the adverse effect of increased IFD. Accordingly, maximum neurite extension from primary neurons is achieved on grooved fibers separated by an IFD of 30 μm, with a higher percentage of aligned neurons on grooved fibers at a large IFD compared to porous fibers with the smallest IFD of 10 µm. We further demonstrate that the neurite “decision-making” behavior on whether to cross a fiber or grow along it is not only dependent on the IFD but also on the fiber surface topography. In addition, axons growing in between the fibers seem to have a memory after leaving grooved fibers, resulting in higher linear growth and higher IFDs lead to more branching. Such information is of great importance for new material development for several tissue engineering applications. Statement of SignificanceOne of the key aspects of tissue engineering is controlling cell behavior using hierarchical structures. Compared to 2D surfaces, fibers are an important class of materials, which can emulate the native ECM architecture of tissues. Despite the importance of both fiber surface topography and alignment to direct growing neurons, the current state of the art did not yet study the synergy between both scales of guidance. To achieve this, we established a solvent assisted spinning process to combine these two crucial features and control neuron growth, alignment, and branching. Rational design of new platforms for various tissue engineering and drug discovery applications can benefit from such information as it allows for fabrication of functional materials, which selectively influence neurite behavior.

Dual-enzymatically crosslinked hyaluronic acid hydrogel as a long-time 3D stem cell culture system

Stem cell-based tissue engineering shows enormous potential for regenerative medicine. Three-dimensional (3D) stem cell culture is the most basic aspect of tissue engineering. However, achievement of a perfect scaffold for highly efficient 3D cell culture is currently still limited. Herein, a new hyaluronic acid hydrogel dual-enzymatically crosslinked by horseradish peroxidase and choline oxidase is developed as a 3D stem cell culture system. This hydrogel possesses superior stability over two months, controllable biodegradability with hyaluronidases, a high swelling ratio exceeding 6000%, and excellent cytocompatibility in vitro and biocompatibility in vivo. More importantly, a long-time and highly cellular activity 3D culture of bone marrow-derived mesenchymal stem cells was achieved in vitro over 20 days. All these encouraging results highlight the great potential of this new hydrogel for 3D culture and tissue engineering.

Biomedical grafts for tracheal tissue repairing and regeneration "Tracheal tissue engineering: an overview".

Airway system is a vital part of the living being body. Trachea is the upper respiratory portion that connects nostril and lungs and has multiple functions such as breathing and entrapment of dust/pathogen particles. Tracheal reconstruction by artificial prosthesis, stents, and grafts are performed clinically for the repairing of damaged tissue. Although these (above-mentioned) methods repair the damaged parts, they have limited applicability like small area wounds and lack of functional tissue regeneration. Tissue engineering helps to overcome the above-mentioned problems by modifying the traditional used stents and grafts, not only repair but also regenerate the damaged area to functional tissue. Bioengineered tracheal replacements are biocompatible, nontoxic, porous, and having 3D biomimetic ultrastructure with good mechanical strength, which results in faster and better tissue regeneration. Till date, the bioengineered tracheal replacements studies have been going on preclinical and clinical levels. Besides that, still many researchers are working at advance level to make extracellular matrix-based acellular, 3D printed, cell-seeded grafts including living cells to overcome the demand of tissue or organ and making the ready to use tracheal reconstructs for clinical application. Thus, in this review, we summarized the tracheal tissue engineering aspects and their outcomes.

Marine Seaweed Polysaccharides-Based Engineered Cues for the Modern Biomedical Sector.

Seaweed-derived polysaccharides with unique structural and functional entities have gained special research attention in the current medical sector. Seaweed polysaccharides have been or being used to engineer novel cues with biomedical values to tackle in practice the limitations of counterparts which have become ineffective for 21st-century settings. The inherited features of seaweed polysaccharides, such as those of a biologically tunable, biocompatible, biodegradable, renewable, and non-toxic nature, urge researchers to use them to design therapeutically effective, efficient, controlled delivery, patient-compliant, and age-compliant drug delivery platforms. Based on their significant retention capabilities, tunable active units, swelling, and colloidal features, seaweed polysaccharides have appeared as highly useful materials for modulating drug-delivery and tissue-engineering systems. This paper presents a standard methodological approach to review the literature using inclusion-exclusion criteria, which is mostly ignored in the reported literature. Following that, numerous marine-based seaweed polysaccharides are discussed with suitable examples. For the applied perspectives, part of the review is focused on the biomedical values, i.e., targeted drug delivery, wound-curative potential, anticancer potentialities, tissue-engineering aspects, and ultraviolet (UV) protectant potential of seaweed polysaccharides based engineered cues. Finally, current challenges, gaps, and future perspectives have been included in this review.

Normal and cancer cells response on the thin films based on chitosan and tannic acid

A novel aspect of tissue engineering is the material selective influence on the different cell types. The cell viability is a parameter which determine the cell ability to proliferate in the contact with material. In the experimental study the thin films based on chitosan and tannic acid mixture in ratio 80/20, 50/50 and 20/80 were tested. The surface roughness decreases with increasing tannic acid content. The cell culture was established on the proposed films. In vitro tests were carried out for the different cell lines as MNT-1, SK-MEL-28, Saos-2, HaCaT and BMSC. The result showed the dependence on the material influence on the various cell lines.

Knee Meniscus Injury: Insights on Tissue engineering Strategies Through Retrospective Analysis and In Silico Modeling

The present work focuses on three main aspects such as (1) extent of surgically managed human meniscal injury problem among the selected population (patients underwent meniscectomy), (2) viability of meniscus cells (isolated from surgical debri) at different age groups, and (3) simulation studies on model scaffolds to understand the biomechanical aspects. Thus, this study gives insights on the severity of the knee meniscus injury in the selected region and tissue engineering aspects which can in turn help in the design and development tissue-engineered construct for the regeneration of damaged tissue. Total 1025 patients (who underwent knee surgery related to meniscal injuries) data were collected from 2012 to 2015. With available additional data, main population was subdivided into two subpopulations. Retrospective and predictive statistical analyses using different statistical tools were performed for gender, age groups, causes of injury, symptoms, pre-treatment symptomatic duration, location of injury, and treatment given. Medium active persons with 23–28 BMI had shown more meniscus damage occurrences in subpopulation 2 (n = 316). 125 meniscus surgical debrises were collected and cells were isolated from the samples to analyze the cell count in each age group. This study showed that as age increases, cell viability was found to be decreased. In this study using simulation studies, the stress distribution against varying applied load was analyzed using COMSOL MULTIPHYSICS (version 4.3b). For this study, two different model scaffold systems were used such as poly(methyl methacrylate) (PMMA) and silicone. This approach can be a strong foundation for the development implantable scaffolds with biomechanical properties comparable to human meniscus.