scholarly journals Translational stem cell therapy: vascularized skin grafts in skin repair and regeneration

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qian Hua Phua ◽  
Hua Alexander Han ◽  
Boon-Seng Soh
Keyword(s):  
Tissue Engineering ◽  
New Technologies ◽  
Rapid Development ◽  
Cell Types ◽  
Skin Tissue ◽  
Skin Substitute ◽  
Specific Cell ◽  
Skin Grafts ◽  
Cell Therapies ◽  
Micro Patterning

AbstractThe skin is made up of a plethora of cells arranged in multiple layers with complex and intricate vascular networks, creating a dynamic microenvironment of cells-to-matrix interactions. With limited donor sites, engineered skin substitute has been in high demand for many therapeutic purposes. Over the years, remarkable progress has occurred in the skin tissue-engineering field to develop skin grafts highly similar to native tissue. However, the major hurdle to successful engraftment is the incorporation of functional vasculature to provide essential nutrients and oxygen supply to the embedded cells. Limitations of traditional tissue engineering have driven the rapid development of vascularized skin tissue production, leading to new technologies such as 3D bioprinting, nano-fabrication and micro-patterning using hydrogel based-scaffold. In particular, the key hope to bioprinting would be the generation of interconnected functional vessels, coupled with the addition of specific cell types to mimic the biological and architectural complexity of the native skin environment. Additionally, stem cells have been gaining interest due to their highly regenerative potential and participation in wound healing. This review briefly summarizes the current cell therapies used in skin regeneration with a focus on the importance of vascularization and recent progress in 3D fabrication approaches to generate vascularized network in the skin tissue graft.

scholarly journals Functional Skin Grafts: Where Biomaterials Meet Stem Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-20 ◽  
Author(s):  
Amtoj Kaur ◽  
Swati Midha ◽  
Shibashish Giri ◽  
Sujata Mohanty
Keyword(s):  
Tissue Engineering ◽  
Cultured Cells ◽  
Clinical Success ◽  
Cell Types ◽  
Skin Tissue ◽  
Patient Specific ◽  
Skin Substitute ◽  
Skin Substitutes ◽  
3D Matrix

Skin tissue engineering has attained several clinical milestones making remarkable progress over the past decades. Skin is inhabited by a plethora of cells spatiotemporally arranged in a 3-dimensional (3D) matrix, creating a complex microenvironment of cell-matrix interactions. This complexity makes it difficult to mimic the native skin structure using conventional tissue engineering approaches. With the advent of newer fabrication strategies, the field is evolving rapidly. However, there is still a long way before an artificial skin substitute can fully mimic the functions and anatomical hierarchy of native human skin. The current focus of skin tissue engineers is primarily to develop a 3D construct that maintains the functionality of cultured cells in a guided manner over a period of time. While several natural and synthetic biopolymers have been translated, only partial clinical success is attained so far. Key challenges include the hierarchical complexity of skin anatomy; compositional mismatch in terms of material properties (stiffness, roughness, wettability) and degradation rate; biological complications like varied cell numbers, cell types, matrix gradients in each layer, varied immune responses, and varied methods of fabrication. In addition, with newer biomaterials being adopted for fabricating patient-specific skin substitutes, issues related to escalating processing costs, scalability, and stability of the constructs under in vivo conditions have raised some concerns. This review provides an overview of the field of skin regenerative medicine, existing clinical therapies, and limitations of the current techniques. We have further elaborated on the upcoming tissue engineering strategies that may serve as promising alternatives for generating functional skin substitutes, the pros and cons associated with each technique, and scope of their translational potential in the treatment of chronic skin ailments.

Needleless electrospinning of PVP/PGS fibrous scaffolds for skin tissue engineering applications

2018 ◽  
Author(s):  
Antonios Keirouz ◽  
Giuseppino Fortunato ◽  
Anthony Callanan ◽  
Norbert Radacsi
Keyword(s):  
Tissue Engineering ◽  
Tensile Modulus ◽  
Dermal Fibroblasts ◽  
Skin Tissue ◽  
Skin Substitute ◽  
Electrospinning Technique ◽  
Skin Tissue Engineering ◽  
Needleless Electrospinning ◽  
High Concentrations

Scaffolds and implants used for tissue engineering need to be adapted for their mechanical properties with respect to their environment within the human body. Therefore, a novel composite for skin tissue engineering is presented by use of blends of Poly(vinylpyrrolidone) (PVP) and Poly(glycerol sebacate) (PGS) were fabricated via the needleless electrospinning technique. The formed PGS/PVP blends were morphologically, thermochemically and mechanically characterized. The morphology of the developed fibers related to the concentration of PGS, with high concentrations of PGS merging the fibers together plasticizing the scaffold. The tensile modulus appeared to be affected by the concentration of PGS within the blends, with an apparent decrease in the elastic modulus of the electrospun mats and an exponential increase of the elongation at break. Ultraviolet (UV) crosslinking of PGS/PVP significantly decreased and stabilized the wettability of the formed fiber mats, as indicated by contact angle measurements. In vitro examination showed good viability and proliferation of human dermal fibroblasts over the period of a week. The present findings provide important insights for tuning the elastic properties of electrospun material by incorporating this unique elastomer, as a promising future candidate for skin substitute constructs.

scholarly journals Immunomodulation of Skin Repair: Cell-Based Therapeutic Strategies for Skin Replacement (A Comprehensive Review)

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 118
Author(s):  
Shima Tavakoli ◽  
Marta A. Kisiel ◽  
Thomas Biedermann ◽  
Agnes S. Klar
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Wound Healing ◽  
Skin Wound ◽  
Skin Tissue ◽  
Diabetic Patients ◽  
Specific Cell ◽  
Skin Substitutes ◽  
Skin Wound Healing ◽  
Skin Tissue Engineering

The immune system has a crucial role in skin wound healing and the application of specific cell-laden immunomodulating biomaterials emerged as a possible treatment option to drive skin tissue regeneration. Cell-laden tissue-engineered skin substitutes have the ability to activate immune pathways, even in the absence of other immune-stimulating signals. In particular, mesenchymal stem cells with their immunomodulatory properties can create a specific immune microenvironment to reduce inflammation, scarring, and support skin regeneration. This review presents an overview of current wound care techniques including skin tissue engineering and biomaterials as a novel and promising approach. We highlight the plasticity and different roles of immune cells, in particular macrophages during various stages of skin wound healing. These aspects are pivotal to promote the regeneration of nonhealing wounds such as ulcers in diabetic patients. We believe that a better understanding of the intrinsic immunomodulatory features of stem cells in implantable skin substitutes will lead to new translational opportunities. This, in turn, will improve skin tissue engineering and regenerative medicine applications.

scholarly journals The new technologies of high-throughput single-cell RNA sequencing

2019 ◽  
Vol 23 (5) ◽  
pp. 508-518
Author(s):  
E. A. Vodiasova ◽  
E. S. Chelebieva ◽  
O. N. Kuleshova
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
High Performance ◽  
New Technologies ◽  
Bioinformatics Analysis ◽  
Single Cells ◽  
Rapid Development ◽  
Cell Types ◽  
Regulatory Pathways ◽  
Sequencing Technologies

A wealth of genome and transcriptome data obtained using new generation sequencing (NGS) technologies for whole organisms could not answer many questions in oncology, immunology, physiology, neurobiology, zoology and other fields of science and medicine. Since the cell is the basis for the living of all unicellular and multicellular organisms, it is necessary to study the biological processes at its level. This understanding gave impetus to the development of a new direction – the creation of technologies that allow working with individual cells (single-cell technology). The rapid development of not only instruments, but also various advanced protocols for working with single cells is due to the relevance of these studies in many fields of science and medicine. Studying the features of various stages of ontogenesis, identifying patterns of cell differentiation and subsequent tissue development, conducting genomic and transcriptome analyses in various areas of medicine (especially in demand in immunology and oncology), identifying cell types and states, patterns of biochemical and physiological processes using single cell technologies, allows the comprehensive research to be conducted at a new level. The first RNA-sequencing technologies of individual cell transcriptomes (scRNA-seq) captured no more than one hundred cells at a time, which was insufficient due to the detection of high cell heterogeneity, existence of the minor cell types (which were not detected by morphology) and complex regulatory pathways. The unique techniques for isolating, capturing and sequencing transcripts of tens of thousands of cells at a time are evolving now. However, new technologies have certain differences both at the sample preparation stage and during the bioinformatics analysis. In the paper we consider the most effective methods of multiple parallel scRNA-seq using the example of 10XGenomics, as well as the specifics of such an experiment, further bioinformatics analysis of the data, future outlook and applications of new high-performance technologies.

COMPUTATIONAL MODELING OF TISSUE SELF-ASSEMBLY

2006 ◽  
Vol 20 (20) ◽  
pp. 1217-1231 ◽  
Author(s):  
ADRIAN NEAGU ◽  
IOAN KOSZTIN ◽  
KAROLY JAKAB ◽  
BOGDAN BARZ ◽  
MONICA NEAGU ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Cell Sorting ◽  
Self Assembly ◽  
Computational Models ◽  
Energy State ◽  
Cell Sheet ◽  
Cell Types ◽  
Specific Cell ◽  
Living Tissues

As a theoretical framework for understanding the self-assembly of living cells into tissues, Steinberg proposed the differential adhesion hypothesis (DAH) according to which a specific cell type possesses a specific adhesion apparatus that combined with cell motility leads to cell assemblies of various cell types in the lowest adhesive energy state. Experimental and theoretical efforts of four decades turned the DAH into a fundamental principle of developmental biology that has been validated both in vitro and in vivo. Based on computational models of cell sorting, we have developed a DAH-based lattice model for tissues in interaction with their environment and simulated biological self-assembly using the Monte Carlo method. The present brief review highlights results on specific morphogenetic processes with relevance to tissue engineering applications. Our own work is presented on the background of several decades of theoretical efforts aimed to model morphogenesis in living tissues. Simulations of systems involving about 105 cells have been performed on high-end personal computers with CPU times of the order of days. Studied processes include cell sorting, cell sheet formation, and the development of endothelialized tubes from rings made of spheroids of two randomly intermixed cell types, when the medium in the interior of the tube was different from the external one. We conclude by noting that computer simulations based on mathematical models of living tissues yield useful guidelines for laboratory work and can catalyze the emergence of innovative technologies in tissue engineering.

scholarly journals Current Perspectives in Mesenchymal Stromal Cell Therapies for Airway Tissue Defects

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Francesco Petrella ◽  
Stefania Rizzo ◽  
Alessandro Borri ◽  
Monica Casiraghi ◽  
Lorenzo Spaggiari
Keyword(s):  
Daily Practice ◽  
Cell Types ◽  
Specific Cell ◽  
Industrialized Countries ◽  
Wound Site ◽  
Cell Therapies ◽  
Airway Diseases ◽  
Paracrine Secretion ◽  
Cardiopulmonary System ◽  
Tissue Defects

Lung cancer is the leading cause of cancer death and respiratory diseases are the third cause of death in industrialized countries; for this reason the airways and cardiopulmonary system have been the focus of extensive investigation, in particular of the new emerging branch of regenerative medicine. Mesenchymal stromal cells (MSCs) are a population of undifferentiated multipotent adult cells that naturally reside within the human body, which can differentiate into osteogenic, chondrogenic, and adipogenic lineages when cultured in specific inducing media. MSCs have the ability to migrate and engraft at sites of inflammation and injury in response to cytokines, chemokines, and growth factors at a wound site and they can exert local reparative effects through transdifferentiation and differentiation into specific cell types or via the paracrine secretion of soluble factors with anti-inflammatory and wound-healing activities. Experimental and clinical evidence exists regarding MSCs efficacy in airway defects restoration; although clinical MSCs use, in the daily practice, is not yet completely reached for airway diseases, we can argue that MSCs do not represent any more merely an experimental approach to airway tissue defects restoration but they can be considered as a “salvage” therapeutic tool in very selected patients and diseases.

Scaffolds for hand tissue engineering: the importance of surface topography

2015 ◽  
Vol 40 (9) ◽  
pp. 973-985 ◽  
Author(s):  
E. Kloczko ◽  
D. Nikkhah ◽  
L. Yildirimer
Keyword(s):  
Tissue Engineering ◽  
Cell Attachment ◽  
Three Dimensional ◽  
Cell Types ◽  
Specific Cell ◽  
Complex Structures ◽  
Research Focus ◽  
Functional Regeneration ◽  
Fully Functioning ◽  
Extracellular Environment

Tissue engineering is believed to have great potential for the reconstruction of the hand after trauma, congenital absence and tumours. Due to the presence of multiple distinct tissue types, which together function in a precisely orchestrated fashion, the hand counts among the most complex structures to regenerate. As yet the achievements have been limited. More recently, the focus has shifted towards scaffolds, which provide a three-dimensional framework to mimic the natural extracellular environment for specific cell types. In particular their surface structures (or topographies) have become a key research focus to enhance tissue-specific cell attachment and growth into fully functioning units. This article reviews the current understanding in hand tissue engineering before focusing on the potential for scaffold topographical features on micro- and nanometre scales to achieve better functional regeneration of individual and composite tissues.

scholarly journals Actually Seeing What Is Going on – Intravital Microscopy in Tissue Engineering

2021 ◽  
Vol 9 ◽  
Author(s):  
Ravikumar Vaghela ◽  
Andreas Arkudas ◽  
Raymund E. Horch ◽  
Maximilian Hessenauer
Keyword(s):  
Tissue Engineering ◽  
Intravital Microscopy ◽  
Ex Vivo ◽  
Cell Types ◽  
3D Models ◽  
Tissue Imaging ◽  
Fluorescence Labeling ◽  
Specific Cell ◽  
Rapid Improvement

Intravital microscopy (IVM) study approach offers several advantages over in vitro, ex vivo, and 3D models. IVM provides real-time imaging of cellular events, which provides us a comprehensive picture of dynamic processes. Rapid improvement in microscopy techniques has permitted deep tissue imaging at a higher resolution. Advances in fluorescence tagging methods enable tracking of specific cell types. Moreover, IVM can serve as an important tool to study different stages of tissue regeneration processes. Furthermore, the compatibility of different tissue engineered constructs can be analyzed. IVM is also a promising approach to investigate host reactions on implanted biomaterials. IVM can provide instant feedback for improvising tissue engineering strategies. In this review, we aim to provide an overview of the requirements and applications of different IVM approaches. First, we will discuss the history of IVM development, and then we will provide an overview of available optical modalities including the pros and cons. Later, we will summarize different fluorescence labeling methods. In the final section, we will discuss well-established chronic and acute IVM models for different organs.

Cell therapy in orthopaedics

2019 ◽  
Vol 101-B (4) ◽  
pp. 361-364 ◽  
Author(s):  
S. A. Rodeo
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Adipose Tissue ◽  
Cell Therapy ◽  
Bone Cells ◽  
Cell Types ◽  
Specific Cell ◽  
Cell Therapies ◽  
Native Bone ◽  
Wide Range

Stem cells are defined by their potential for self-renewal and the ability to differentiate into numerous cell types, including cartilage and bone cells. Although basic laboratory studies demonstrate that cell therapies have strong potential for improvement in tissue healing and regeneration, there is little evidence in the scientific literature for many of the available cell formulations that are currently offered to patients. Numerous commercial entities and ‘regenerative medicine centres’ have aggressively marketed unproven cell therapies for a wide range of medical conditions, leading to sometimes indiscriminate use of these treatments, which has added to the confusion and unpredictable outcomes. The significant variability and heterogeneity in cell formulations between different individuals makes it difficult to draw conclusions about efficacy. The ‘minimally manipulated’ preparations derived from bone marrow and adipose tissue that are currently used differ substantially from cells that are processed and prepared under defined laboratory protocols. The term ‘stem cells’ should be reserved for laboratory-purified, culture-expanded cells. The number of cells in uncultured preparations that meet these defined criteria is estimated to be approximately one in 10 000 to 20 000 (0.005% to 0.01%) in native bone marrow and 1 in 2000 in adipose tissue. It is clear that more refined definitions of stem cells are required, as the lumping together of widely diverse progenitor cell types under the umbrella term ‘mesenchymal stem cells’ has created confusion among scientists, clinicians, regulators, and our patients. Validated methods need to be developed to measure and characterize the ‘critical quality attributes’ and biological activity of a specific cell formulation. It is certain that ‘one size does not fit all’ – different cell formulations, dosing schedules, and culturing parameters will likely be required based on the tissue being treated and the desired biological target. As an alternative to the use of exogenous cells, in the future we may be able to stimulate the intrinsic vascular stem cell niche that is known to exist in many tissues. The tremendous potential of cell therapy will only be realized with further basic, translational, and clinical research. Cite this article: Bone Joint J 2019;101-B:361–364.

scholarly journals Lattice and continuum modelling of a bioactive porous tissue scaffold

2018 ◽  
Vol 36 (3) ◽  
pp. 325-360 ◽  
Author(s):  
Andrew L Krause ◽  
Dmitry Beliaev ◽  
Robert A Van Gorder ◽  
Sarah L Waters
Keyword(s):  
Tissue Engineering ◽  
Cell Growth ◽  
Network Structure ◽  
Lattice Model ◽  
Porous Scaffold ◽  
Cell Types ◽  
Specific Cell ◽  
Tissue Scaffold ◽  
Biomaterial Scaffold ◽  
Model Cell

AbstractA contemporary procedure to grow artificial tissue is to seed cells onto a porous biomaterial scaffold and culture it within a perfusion bioreactor to facilitate the transport of nutrients to growing cells. Typical models of cell growth for tissue engineering applications make use of spatially homogeneous or spatially continuous equations to model cell growth, flow of culture medium, nutrient transport and their interactions. The network structure of the physical porous scaffold is often incorporated through parameters in these models, either phenomenologically or through techniques like mathematical homogenization. We derive a model on a square grid lattice to demonstrate the importance of explicitly modelling the network structure of the porous scaffold and compare results from this model with those from a modified continuum model from the literature. We capture two-way coupling between cell growth and fluid flow by allowing cells to block pores, and by allowing the shear stress of the fluid to affect cell growth and death. We explore a range of parameters for both models and demonstrate quantitative and qualitative differences between predictions from each of these approaches, including spatial pattern formation and local oscillations in cell density present only in the lattice model. These differences suggest that for some parameter regimes, corresponding to specific cell types and scaffold geometries, the lattice model gives qualitatively different model predictions than typical continuum models. Our results inform model selection for bioactive porous tissue scaffolds, aiding in the development of successful tissue engineering experiments and eventually clinically successful technologies.

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