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3D bioprinting shows significant promise for creating complex tissue and organ mimics to solve transplant needs and to provide platforms for drug testing and studying tissue morphogenesis[1][2][3]. However, the lack of 3D printable and cell-compatible bioinks as well as the limited ability to tune bioink material properties are cited as significant inhibitors to the growth of bioprinting[4][5]. Pioneers in the field of tissue engineering and biomaterials have established and validated that changing materials properties such as stiffness[6], bioactive moieties[7][8], and degradation[7][9] significantly impacts cell behavior and tissue formation. Thus, developing novel, versatile and tunable bioink methods that will facilitate advanced material and construct design will have important implications in the field of bioprinting and biofabrication. Versatile bioink synthesis techniques, ones that can be used with many materials, will improve both printability of existing bioinks and most importantly, can add completely new biomaterials to the 3D bioprinting material palette. Furthermore, development of tunable bioink methods will provide additional means to customize mechanical, chemical, physical, and biological properties of printed structures towards creating compositionally and structurally complex structures and functional tissues beyond the rudimentary tissue structures presented thus far.

Tissue engineering recovers an original function of tissue by replacing the damaged part with a new tissue or organ regenerated using various engineering technologies. This technology uses a scaffold to support three-dimensional (3D) tissue formation. Conventional scaffold fabrication methods do not control the architecture, pore shape, porosity, or interconnectivity of the scaffold, so it has limited ability to stimulate cell growth and to generate new tissue. 3D printing technologies may overcome these disadvantages of traditional fabrication methods. These technologies use computers to assist in design and fabrication, so the 3D scaffolds can be fabricated as designed and standardized. Particularly, because nanofabrication technology based on two-photon absorption (2PA) and on controlled electrospinning can generate structures with submicron resolution, these methods have been evaluated in various areas of tissue engineering. Recent combinations of 3D nanoprinting technologies with methods from molecular biology and cell dynamics have suggested new possibilities for improved tissue regeneration. If the interaction between cells and scaffold system with biomolecules can be understood and controlled and if an optimal 3D environment for tissue regeneration can be realized, 3D nanoprinting will become an important tool in tissue engineering.

Sirtuins (SIRTs) are initially recognized as NAD+-dependent histone deacetylase. SIRTs attract attention for their role as calorie restriction-induced “longevity proteins” to be expected to extend human life span and to promote health. As advancing studies, SIRTs have been recognized as cell signaling regulators which contribute to anti-inflammation, cell differentiation and so on. Therefore, SIRTs are supposed to affect wound healing which is comprised highly orchestrated complex four phases: hemostasis, inflammation, tissue formation and tissue remodeling. This review highlights the roles of SIRTs in wound healing process and provides a foundation and impetus for future basic and clinical research.

The cadherin family of cell-cell adhesion molecules plays a pivotal role in animal tissue formation. Discovery of this molecular family can be traced back to some unexpected observations of strange cell behavior that were made around 1970 in the Kyoto University laboratory of Tokindo Okada, and then in the Department of Embryology at the Carnegie Institution of Washington (currently the Carnegie Institution for Science). This article looks back on these discoveries, and recalls how these observations led to the identification of important cell-cell adhesion molecules known as cadherins.

Scaffold-free systems have emerged as viable approaches for engineering load-bearing tissues. However, the tensile properties of engineered tissues have remained far below the values for native tissue. Here, by using self-assembled articular cartilage as a model to examine the effects of intermittent and continuous tension stimulation on tissue formation, we show that the application of tension alone, or in combination with matrix remodelling and synthesis agents, leads to neocartilage with tensile properties approaching those of native tissue. Implantation of tension-stimulated tissues results in neotissues that are morphologically reminiscent of native cartilage. We also show that tension stimulation can be translated to a human cell source to generate anisotropic human neocartilage with enhanced tensile properties. Tension stimulation, which results in nearly sixfold improvements in tensile properties over unstimulated controls, may allow the engineering of mechanically robust biological replacements of native tissue.

Influence of gelatine concentration and cross-linker ions of Ca2+ and Ba2+ was evaluated on characteristics of alginate hydrogels and proliferation behaviours of model adherent and suspendable stem...

Wnt signaling regulates many aspects of vertebrate development. Its dysregulation causes developmental defects and diseases including cancer. The signaling can be categorized in two pathways: canonical and noncanonical. Canonical pathway plays a key role in regulating proliferation and differentiation of cells whilst noncanonical Wnt signaling mainly controls cellular polarity and motility. During development, noncanonical Wnt signaling is required for tissue formation. Recent studies have shown that noncanonical Wnt signaling is involved in adult tissue development and cancer progression. In this review, we try to describe and discuss the mechanisms behind the biological effects of noncanonical Wnt signaling, diseases caused by its dysregulation, and implications in adult tissue development biology.

Bone is a living part of the body that can, in most situations, heal itself after fracture. However, in some situations, healing may fail. Compromised conditions, such as large bone defects, aging, immuno-deficiency, or genetic disorders, might lead to delayed or non-unions. Treatment strategies for those conditions remain a clinical challenge, emphasizing the need to better understand the mechanisms behind endogenous bone regeneration. Bone healing is a complex process that involves the coordination of multiple events at different length and time scales. Computer models have been able to provide great insights into the interactions occurring within and across the different scales (organ, tissue, cellular, intracellular) using different modeling approaches [partial differential equations (PDEs), agent-based models, and finite element techniques]. In this review, we summarize the latest advances in computer models of bone healing with a focus on multiscale approaches and how they have contributed to understand the emergence of tissue formation patterns as a result of processes taking place at the lower length scales.

Complications resulting from impaired fracture healing have major clinical implications on fracture management strategies. Novel concepts taken from developmental biology have driven research strategies towards the elaboration of regenerative approaches that can truly harness the complex cellular events involved in tissue formation and repair. Advances in polymer technology and a better understanding of naturally derived scaffolds have given rise to novel biomaterials with an increasing ability to recapitulate native tissue environments. This coupled with advances in the understanding of stem cell biology and technology has opened new avenues for regenerative strategies with true clinical translatability. These advances have provided the impetus to develop alternative approaches to enhance the fracture repair process. We provide an update on these advances, with a focus on the development of novel biomimetic approaches for bone regeneration and their translational potential.

In caudal autotomy, lizards shed their tail to escape from an attacking predator. Since the tail serves multiple functions, caudal regeneration is of pivotal importance. However, it is a demanding procedure that requires substantial energy and nutrients. Therefore, lizards have to increase energy income to fuel the extraordinary requirements of the regenerating tail. We presumed that autotomized lizards would adjust their digestion to acquire this additional energy. To clarify the effects of tail regeneration on digestion, we compared the digestive performance before autotomy, during regeneration, and after its completion. Tail regeneration indeed increased gut passage time but did not affect digestive performance in a uniform pattern: though protein income was maximized, lipid and sugar acquisition remained stable. This divergence in proteins may be attributed to their particular role in tail reconstruction, as they are the main building blocks for tissue formation.

We present the results of fabricating micro-structured macro-constructs for tissue engineering applications by using direct laser writing in pre-polymers (DLW-PP). The limiting factors for rapid construction of millimeter sized scaffolds, including the choice of material, software and hardware, as well as geometry, are discussed. We demonstrate that by using the hybrid inorganic-organic pre-polymer SZ2080 and employing a laser system which can combine the movement of linear motion stages with scanners, the structuring throughput reaching up to 51300 μm3/s can be achieved maintaining structural elements with 15 μm resolution. This allows to construct up to 30 scaffolds overnight with measurements reaching 1515×1515×195 μm3 – big enough for a surgeon to handle – and enables serial fabrication of such structures required for statistical tissue formation studies. Also, the versatility of DLW-PP technique is demonstrated by presenting the fabricated scaffolds with different pore shapes and sizes as well as manufactured out of pure and photo-sensitized SZ2080 material.

Microfabricated systems and microfluidic tools are well-suited to interface with cells because of the matching length scales. In this issue, we highlight three recent papers in which unique tools were used to control or measure cell migration. Cell migration is a key biological process involved in normal physiology (e.g. in embryonic development, immune response, and wound healing) which can go awry in diseases such as cancer. We highlight work applying electric fields and surface patterning to direct the collective migration of epithelial cells using galvanotaxis, in which surprisingly larger patches of cells respond more uniformly to electric fields. Such a platform may yield insights into or be co-opted to control tissue formation. We also describe recent results on developing a simple system to measure the migration of neutrophils in response to chemoattractants and on using this system to discriminate between neutrophils from asthmatic and non-asthmatic patients. Finally, a micropillar system is highlighted in which the epithelial-to-mesenchymal transition is quantified at the single-cell level, and may aid in our understanding of the plastic process of progression to a malignant phenotype. Cell migration is a wonderfully complex process in which microscale systems can not only contribute to a better understanding, but might also improve its recording and manipulation for practical applications.

To address the increasing need for improved tissue substitutes, tissue engineering seeks to create synthetic, three-dimensional scaffolds made from polymeric materials, incorporating cells and growth factors to induce new tissue formation. Materials science, in conjunction with biotechnology, can satisfy these needs by developing artificial, synthetic substitutes and organ implants. Here, scaffold ability to promote cell growth and differentiation is a key point and, in this framework, orthogonal chemistry has led the field of biomaterial science into a new area of selective, versatile and biocompatible nature. In particular, the possibility to modify and functionalize scaffolds with compounds that are able to improve mechanical properties or cell viability and improve their differentiation in a tailorable manner opens new opportunities for researchers. In this review, we seek to emphasize the recent endeavors of exploiting this versatile chemistry toward the development of new cell culture scaffolds.

The ability to predict and guide stem cell differentiation remains a major challenge in regenerative medicine. Numerous dynamic microenvironmental cues often provide synergistic or combinatorial signals that influence the fate of stem cells, and ultimately drive functional tissue formation. This interplay between microenvironmental cues within tissues is under intense investigation. Our goal was to better understand this interplay within the framework of a systematic 3D platform that would enable high-throughput screening (HTS) of factors that contribute to stem cell fate decisions. It is important that such platforms provide valid biomimetic microenvironments, which can be translated to macroscale constructs. Specifically, we reported on a technique for screening of combinatorial 3D niches to guide the osteogenic differentiation of human mesenchymal stem cells (hMSCs). This platform offers a rapid, cost-effective and multiplexed approach for a variety of tissue engineering applications.

• Premise of the study: Martyniaceae are characterized by capsules with two upwardly curved, horn-shaped extensions representing morphologically specialized epizoochorous fruits. Because the capsules are assumed to cling to hooves and ankles of large mammals, fiber arrangement and tissue combinations within the endocarp ensuring proper attachment to the vector's feet during transport are of particular interest. In this first detailed anatomical investigation, the functional adaptation of the fruits and their implications for the specific dispersal mode are provided. The peculiar fiber arrangement may also be of interest for future biomimetic composite materials.• Methods: Endocarp anatomy and details of tissue differentiation were examined in fruits of Ibicella lutea and Proboscidea louisianica subsp. fragrans combining light microscopy, SEM, and x-ray microtomography analysis.• Key results: While tips of the extensions are predominantly reinforced by longitudinally oriented fibers, in the middle segment these fibers are densely packed in individual bundles entwined and separated by transversely elongated cells. Within the capsule wall, the fiber bundles are embedded in a dense mesh of transversely oriented fibers that circularly reinforce and protect the loculus. This fibrous pericarp tissue develops within few days by localized cell divisions and intrusive growth of primarily isodiametric parenchyma cells in the pistil.• Conclusions: The study allows insight into a unique and complex example of functionally driven cell growth and tissue formation. Long-horned fruits of Martyniaceae obviously are highly specialized to epizoochorous dispersal, pointing to primary vector-related seed dispersal. The highly ordered arrangement of fibers results in a great mechanical firmness.

Highly hierarchical pore structure (macro–micro–nano) for biomimetic nanofibrous scaffolds could efficiently enhance cell infiltration and tissue formation. However, it is difficult to prepare these structures by using traditional electrostatic spinning techniques. Here, we report a facile method to fabricate polycaprolactone (PCL) nanofibrous scaffolds with multi-scale pore structure by simple phase separation. By employing water–dioxane as solvents and tris spheres as macropore template, PCL nanofibrous scaffolds with pores 300–800 µm, 1–10 µm and 100–1000 nm in diameter can be facilely produced. All scaffolds possess controlled nanofibrous morphology and porosity (90–98%). This scaffold may provide promising applications in tissue engineering and drug delivery.

During organogenesis, various molecular and physical signals are orchestrated in space and time to sculpt multiple cell types into functional tissues and organs. The complex and dynamic nature of the process has hindered studies aimed at delineating morphogenetic mechanisms in vivo, particularly in mammals. Recent demonstrations of stem cell-driven tissue assembly in culture offer a powerful new tool for modeling and dissecting organogenesis. However, despite the highly organotypic nature of stem cell-derived tissues, substantial differences set them apart from their in vivo counterparts, probably owing to the altered microenvironment in which they reside and the lack of mesenchymal influences. Advances in the biomaterials and microtechnology fields have, for example, afforded a high degree of spatiotemporal control over the cellular microenvironment, making it possible to interrogate the effects of individual microenvironmental components in a modular fashion and rapidly identify organ-specific synthetic culture models. Hence, bioengineering approaches promise to bridge the gap between stem cell-driven tissue formation in culture and morphogenesis in vivo, offering mechanistic insight into organogenesis and unveiling powerful new models for drug discovery, as well as strategies for tissue regeneration in the clinic. We draw on several examples of stem cell-derived organoids to illustrate how bioengineering can contribute to tissue formation ex vivo. We also discuss the challenges that lie ahead and potential ways to overcome them.

Corky tissue incidence in sapota fruit during the summer months increased in direct proportion to the intensity and duration of stress showing a possible link between drought stress and corky tissue development. Corky tissue incidence was enhanced when the growth of newly initiated shoot buds was promoted by the application of gibberellic acid and reduced when it was inhibited by paclobutrazol, indicating that newly initiated shoots were competing with developing fruits for water and assimilates. An enhanced reverse flow of water and nutrients from fruit to newly initiated shoot buds was found to be the principal contributing factor for the increased incidence of corky tissue in sapota under drought stress.

The treatment of complex wounds is difficult and not always effective. Various treatment options are used with varying degrees of success. Negative pressure wound therapy (NPWT) is a cost-efficient and effective way to help treat these wounds. The use of a vacuum device applies the negative pressure to the site of the wound and promotes waste removal and increases circulation and tissue formation. While various NPWT systems are currently on the market, we utilised the ConvaTec Engenex® system with Bio-Dome™ technology; however, our case study is not intended to advocate the specific use of this system, but instead focusses on the use of NPWT as a viable option for wound healing. Each of the following case study patients presented with difficult-to-heal wounds that failed traditional therapeutic approaches. Through the use of NPWT, our patients saw major wound size reductions. Each patient exhibited at least a 94% reduction in wound area, wound volume or both.

The formation of tissue produced by implanted cells is influenced greatly by the scaffold onto which they are seeded. In the long term it is often preferable to use a biodegradable material scaffold so that all the implanted materials will disappear, leaving behind only the generated tissue. Research in this area has identified several natural biodegradable materials. Among them, hydrogels are receiving increasing attention due to their ability to retain a great quantity of water, their good biocompatibility, their low interfacial tension, and the minimal mechanical and frictional irritation that they cause. Biocompatibility is not an intrinsic property of materials; rather it depends on the biological environment and the tolerability that exists with respect to specific polymer-tissue interactions. The most often utilized biodegradable synthetic polymers for 3D scaffolds in tissue engineering are saturated poly-a-hydroxy esters, including poly(lactic acid) (PLA) and poly(glycolic acid) (PGA), as well as poly(lactic-co-lycolide) (PLGA) copolymers. Hard materials provide compressive and torsional strength; hydrogels and other soft composites more effectively promote cell expansion and tissue formation. This review focuses on the future potential for understanding the characteristics of the biomaterials considered evaluated for clinical use in order to repair or to replace a sizable defect by only harvesting a small tissue sample.

Objetivo: Buscar na literatura cientifica evidências sobre uso da terapia por pressão negativa no tratamento de feridas. Metodologia: O estudo refere-se a uma revisão integrativa da literatura, a busca dos artigos foi realizada nas bases de dados PubMed da National Library of Medicine e Biblioteca Virtual em Saúde através da associação dos seguintes descritores: Ferimentos e lesões, lesões, técnicas de fechamento de ferimentos. Foram inclusos no estudo os artigos primários, disponíveis em sua totalidade, publicados nos últimos 5 anos, em qualquer idioma que atendessem a temática do estudo e excluído da pesquisa os capítulos de livros, resumos, textos incompletos, teses, dissertações e relatos técnicos. Resultado: A terapia por pressão negativa é um método terapêutico eficaz no tratamento das feridas crônicas e agudas, complexas e infectadas. O método permitindo maior controle sobre o ambiente da ferida reduzindo o edema, removendo exsudato e material infeccioso, além de possibilitar a utilização de soluções tópicas diretamente nos tecidos afetados, criando assim um ambiente favorável para a cicatrização de feridas por dá estimulação da formação de tecido de granulação e perfusão. Conclusão: Conclui-se que a terapia por pressão negativa revolucionou o tratamento de feridas, em especial ao tratamento das feridas mais complexas por ajudar a reduzir o tempo de fechamento da ferida e o tempo de permanência hospitalar.

Background and objectivePink gingival esthetics, especially in the anterior teeth, has been an important success criterion in implant-supported restoration. The factor vital to the esthetic success, in the anterior maxillary implants, is the soft tissue profile, which should replicate that of the natural healthy tooth. The absence of the interimplant papilla causes an interimplant black triangle thus leading to cosmetic deformities, phonetic difficulty and food impaction. True papilla regeneration is not possible because the peri-implant soft tissue does not have the same structure as that of the periodontium and, therefore, the term ‘papilla-like’ tissue formation or ‘implant papilla’ is used. This resultant ‘implant papilla’ is the product of soft tissue depth and volume and has to be skilfully surgically created. However, reconstructing a predictable peri-implant papilla is the most complex and challenging aspect of implant dentistry. This article presents a review of various innovative surgical techniques to reconstruct interimplant papilla.How to cite this articleRajguru SA, Pathak TS, Padhye AM, Kanagotagi S, Gupta HS, Rathod AA. Interimplant Papilla Reconstruction. J Contemp Dent 2014;4(1):30-40.

Magnetic nanoparticles have been subjected to extensive studies in the past few decades owing to their promising potentials in biomedical applications. The versatile intrinsic properties of magnetic nanoparticles enable their use in many biomedical applications. Recently, magnetic nanoparticles were utilized to control the cell's function. In addition, intracellular delivery of magnetic nanoparticles allowed cell's positioning by appropriate use of magnetic field and created cellular cluster. Furthermore, magnetic nanoparticles have been utilized to assemble more complex tissue structures than those that are achieved by conventional scaffold-based tissue engineering strategies. This review addresses recent work in the use magnetic nanoparticle for controlled tissue assembly and complex tissue formation.

Transplantation of tissues and organs is currently the only available treatment for patients with end-stage diseases. However, its feasibility is limited by the chronic shortage of suitable donors, the need for life-long immunosuppression, and by socioeconomical and religious concerns. Recently, tissue engineering has garnered interest as a means to generate cell-seeded three-dimensional scaffolds that could replace diseased organs without requiring immunosuppression. Using a regenerative approach, scaffolds made by synthetic, nonimmunogenic, and biocompatible materials have been developed and successfully clinically implanted. This strategy, based on a viable and ready-to-use bioengineered scaffold, able to promote novel tissue formation, favoring cell adhesion and proliferation, could become a reliable alternative to allotransplatation in the next future. In this article, tissue-engineered synthetic substitutes for tubular organs (such as trachea, esophagus, bile ducts, and bowel) are reviewed, including a discussion on their morphological and functional properties. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 2427–2447, 2014

Endogenous markers are a valuable indicator of individual animal ecology, but data interpretation requires a detailed understanding of the timing of tissue formation. Fur is commonly used in bat research using endogenous markers, but the moulting cycles of most bat species are not well documented. In this review, we (i) describe methods of investigating bat moulting; (ii) summarize the current literature on bat moulting cycles, highlighting broad trends; (iii) discuss knowledge gaps; and (iv) make recommendations for optimal fur sampling protocols. Three characteristics may indicate moulting in bats: changing skin pigmentation; visible fur growth and colour changes; and endogenous markers. Most studies reported new fur growth once annually during summer–fall, although there were exceptions. The timing of new fur growth varies among species, sexes, and age classes. Individuals commonly experience asynchronous new fur growth, with dorsal fur growth occurring before ventral. Specific moult progressions vary among species. Knowledge gaps include moulting cycles in tropical species and in subadult and yearling bats; migration during new fur growth; and the timing of fur growth compared with shedding. We recommend that fur samples taken dorsally from adult males are the most likely to be representative of the bat’s site of summer residency.

This study compared crosslinked dextrans in hydroxylpropyl methycellulose (DiHMs, pH 5 or 7) with polymethylmethacrylate in bovine collagen (PMMA) and hyaluronic acid (HA) fillers on soft tissue augmentation and safety in rats. HA tended to maintain its size throughout the experimental period but was moveable and friable because of a lack of thick fibroconnective tissue formation. Although, PMMA induced moderately thick fibroconnective tissue formation, its size was decreased markedly from 3-week postimplantation (PI) and became the smallest at 24-month PI. DiHM (pH 7) elicited strong fibrous encapsulation around the filler. Its size decreased slowly but was still considerably maintained at 24-month PI. In contrast, the rate of the DiHM (pH 5) size decrease was slower than that of PMMA, faster DiHM (pH 7), but comparable to HA. Immunohistochemically, types I and III collagens were deposited inside and outside DiHMs (pH 5 and 7). DiHMs (pH 5 and 7), PMMA, and HA showed no adverse reactions. These results suggest that DiHM (pH 7) assures efficacy and safety and is a good candidate for soft tissue augmentation in both humans and animals.

The field of tissue engineering and regenerative medicine (TERM) has exploded in the last decade. In this Year (or so) in Review, we highlight some of the high impact advances within the field over the past several years. Using the past as our guide and starting with an objective premise, we attempt so to identify recent “hot topics” and transformative publications within the field. Through this process, several key themes emerged: (1) tissue engineering: grafts and materials, (2) regenerative medicine: scaffolds and factors that control endogenous tissue formation, (3) clinical trials, and (4) novel cell sources: induced pluripotent stem cells. Within these focus areas, we summarize the highly impactful articles that emerged from our objective analysis and review additional recent publications to augment and expand upon these key themes. Finally, we discuss where the TERM field may be headed and how to monitor such a broad-based and ever-expanding community.

Biofabrication techniques offer the potential to produce living three-dimensional (3D) tissue constructs to repair or replace damaged or diseased human tissues and organs. Using these advanced Biofabrication techniques, constructs exhibiting spatial variation of cells, cellular building blocks, growth factors, and mechanical properties along multiple axes with high geometric complexity can be obtained. The level of control offered by these technologies to develop complex biofabricated tissues will allow tissue engineers to better study factors that modulate tissue formation and function, and provide a valuable tool to study graft performance as well as for high throughput screening of drug candidates in biofabricated tissue organoid models.

The content of this article is a proprioception to form for the reader an overview of the basic bone regeneration biology and a comprehensive overview of the first principle of bone tissue engineering with a focus of scaffold-based concepts. The contemporary conventional scaffold design literature in which the objective of the research groups was to match exactly the mechanical and morphological properties is reviewed critically. Based on this background the scientific rationale is presented why the progressive, innovative, and creative scaffold designer group has led to a paradigm shift in the field of scaffold-based bone tissue engineering. In this 21st century concepts, the scaffold design is rooted in that the physical and biochemical properties should be in resonance to guide the tissue formation which takes place over 3–6 months into the direction of bone regeneration and finally remodeling and maturation. The article concludes with a section which discusses the key points to translate bone tissue engineering concepts from bench to bedside.

The hypothalamic-pituitary system is essential for maintaining homeostasis by controlling systemic hormones. However, it can be disrupted by various diseases, resulting in lifelong serious symptoms.

Cardiovascular diseases are the major cause of human mortality worldwide. Therefore, cardiac tissue engineering has emerged as a therapeutic approach to develop bioengineered constructs that can be potentially implanted in order to provide support to the damaged cardiac tissue and restore heart function. One of the promising strategies in cardiac tissue engineering relies on nanostructured scaffolds supplemented with biomolecules mimicking the native ECM architecturally and biochemically to promote cell functions and cardiac tissue formation. Therefore, electrospun nanofibers have found various applications as the cardiac patches, drug delivery systems, heart valve prosthesis, etc. This chapter aims to review the applications of the electrospun scaffolds in cardiac tissue engineering.

Movement is the main characteristic of living species and is the major source of biologically inspired computational systems. The migration of cell organism can take the form of either movement of cells or movement within cells, and it is also capable of changing the shape as a result of reversible or irreversible contraction. This paper simulates synergistic fibroblast optimization (SFO), a multi-agent heuristic technique that models the migration and methodical behavior of the fibroblast. The proposed SFO technique exhibits the role of fibroblast in dermal wound healing process, by migrating the individual cell through the connective tissue, and synthesizes the collagen in the extracellular matrix for the new tissue formation during wound healing. Compared to the related technique particle swarm optimization (PSO), SFO produces better results in terms of both accuracy and performance. An analysis of the proposed algorithm indicates that the two most important factors contributing to SFO effectiveness are fibroblast collaborative nature and goal-oriented feature. The results suggest that SFO is a promising new optimization technique, which may be particularly applicable to find optimal maxima or minima, among the candidate solutions in the nonlinear complicated optimization problem.

The influence of two morphactins (IT 3233 and IT 3456) on the formation of tissues in sunflower leaves was investigated. The leaves were usually smaller, they had plicate laminae and rolled up edges. The different influence of morphactins in dependence on the position of the leaves on the stem and on the kind of tissues was confirmed. Leaves growing from the first node had the thickest laminae, main ribs and the longest cells of palisade parenchyma. The values contrasted with those in the leaves from the third node. An increase of the number of epidermis cells and stomata in leaves from the first and second node and a decrease in those from the third node were observed. Additional layers (1-2) of palisade parenchyma in leaves of the second and third node were formed. Mesophyll was very compact. Xylem consisted of a greater number of elements, arranged compactly and of much lower diameter.

Fetal wounds have been found to have increased levels of high-molecular-weight hyaluronan (HMW-HA) compared with those of adults. The primary enzyme responsible for producing HMW-HA is hyaluronic acid synthase-1 (HAS-1). We hypothesized that over-expression of HAS-1 in adult dermal wounds would decrease inflammation and promote regenerative healing. To test this hypothesis, the flanks of adult C57Bl/6 mice were treated with a lentiviral construct containing either HAS-1-GFP or GFP transgenes. After 48 h, a 4-mm excisional wound was made at the site of treatment. Wounds were harvested at days 3, 7, or 28 after wounding. Wound phenotype was assessed by histology to examine tissue architecture and immunohistochemistry for CD45. At 7 and 28 days, lenti-HAS-1-treated wounds demonstrated the restoration of the normal dermal elements and organized collagen fiber orientation. In contrast, the lenti-GFP-treated wounds lacked normal dermal architecture and demonstrated a disorganized collagen scar. At 3 and 7 days, wounds treated with lenti-HAS-1 exhibited a significant decrease in the number of inflammatory cells when compared with wounds treated with lenti-GFP. Thus, HAS-1 over-expression promotes dermal regeneration, in part by decreasing the inflammatory response and by recapitulation of fetal extracellular matrix HMW-HA content.

Computational modeling is usually employed for simulation, design and manufacturing of tissue scaffolds, specially focused on macroscopic and microscopic properties, relying on anatomy and geometrical constraints. However, these models typically require to take into account the effects of cell-matrix interaction due to its crucial influence on a range of cellular processes including cell adhesion, differentiation and tissue formation among others. Computational mechano-chemo-biology is a numerical approach that aims to consider this interaction by means of a multiphysics and/or a multiscale computer framework. This article reviews some of the recent progress made in modeling bone regeneration induced by scaffolds, taking into account cell-matrix interactions. The issues covered in this work include different kind of numerical models at different length scales that go from cell-matrix interaction to tissue mechanics. The review concludes summarizing the main challenges that researchers face to consolidate modeling as a final design tool for tissue engineering.

Tissue engineering (TE) has made stark advancements through a greater understanding of the effects of various biomaterials on cell behavior and mediated tissue formation. Human tissue can be readily classified as a nanocomposite owing to the presence of nanoscale organic and/or inorganic constituents found within the extracellular matrix. Research has begun and continues to leverage this understanding in an effort to fabricate more biomimetic nanobiomaterials, which share similar composition and morphology to native tissue components. In addition, novel three-dimension (3D) scaffold manufacturing techniques are being developed to extend the use of these novel materials toward the development of clinically relevant scaffolds exhibiting not only similar composition, but spatial distribution of tissue-specific extracellular components. Interfacial and complex tissue regeneration applications including those related to osteochondral (bone-cartilage interface) regeneration stand to benefit greatly from these advancements. Through the course of this chapter we will explore the most recent developments in nanobiomaterials for osteochondral tissue as well as introduce and discuss 3D bioprinting platforms and techniques for the fabrication of biomimetic scaffolds.

The culture of cells in a three-dimensional (3D) scaffold has been reported as a key issue influencing the newly formed tissue organization, either in vitro or in vivo. Scaffolds can present different material chemistry, geometry, structure, physical properties and degradation, as it has been explored in several chapters of this book. Herein, we intend to give the reader an overview of the most used tests for evaluation of cells cytotoxicity and their response to natural materials in vitro., (undefined), info:eu-repo/semantics/publishedVersion

In the field of cartilage tissue engineering, filter cultures are a frequently used three-dimensional differentiation model. However, understanding of the governing processes of in vitro growth and development of tissue in these models is limited. Therefore, this study aimed to further characterise these processes by means of an approach combining both experimental and applied mathematical methods. A mathematical model was constructed, consisting of partial differential equations predicting the distribution of cells and glycosaminoglycans (GAGs), as well as the overall thickness of the tissue. Experimental data was collected to allow comparison with the predictions of the simulation and refinement of the initial models. Healthy mature equine chondrocytes were expanded and subsequently seeded on collagen-coated filters and cultured for up to 7 weeks. Resulting samples were characterised biochemically, as well as histologically. The simulations showed a good representation of the experimentally obtained cell and matrix distribution within the cultures. The mathematical results indicate that the experimental GAG and cell distribution is critically dependent on the rate at which the cell differentiation process takes place, which has important implications for interpreting experimental results. This study demonstrates that large regions of the tissue are inactive in terms of proliferation and growth of the layer. In particular, this would imply that higher seeding densities will not significantly affect the growth rate. A simple mathematical model was developed to predict the observed experimental data and enable interpretation of the principal underlying mechanisms controlling growth-related changes in tissue composition.

Mechanochemical models based on the Oster-Murray continuum framework have been applied to a variety of biological settings to obtain an understanding of the morphogenesis of living tissues. Wound-healing in mammalian skin is an important example, because a complex sequence of biochemical and biomechanical responses are orchestrated to close a wound by a combination of new tissue formation and wound contraction. Mechanical interactions between dermal fibroblastic cells and the collagen-rich extracellular matrix are crucial in the development of a contracted wound state. We and others have previously proposed mechanochemical models for wound repair to gain a greater understanding of both normal and abnormal healing. In the present work, the existence of spatially varying equilibria of these models is investigated by using a small-stain approximation and phase-plane techniques, with numerical simulations to confirm the analytical predictions. These results are sources of novel insight into the roles of key biological parameters in determining the mechanical properties of a contracted wound. These methods may also be relevant to other morphogenetic scenarios for which similar mechanochemical models have been proposed.

Recent advancements in materials science and engineering may hold the key to overcoming reproducibility and scalability limitations currently hindering the clinical translation of stem cell therapies. Biomaterial assisted differentiation commitment of stem cells and modulation of their in vivo function could have a significant impact on stem cell-centred regenerative medicine approaches and next generation technological platforms. Synthetic biomaterials are of particular interest as they provide a consistent, chemically defined, and tunable way of mimicking the physical and chemical properties of the natural tissue or cell environment. Combining the emerging biomaterial and biofabrication advancements may finally give researchers the tools to modulate spatiotemporal complexity and engineer more hierarchically complex, physiologically relevant tissue mimics. In this review we highlight recent research advancements in biomaterial assisted pluripotent stem cell (PSC) expansion and three dimensional (3D) tissue formation strategies. Furthermore, since vascularization is a major challenge affecting the in vivo function of engineered tissues, we discuss recent developments in vascularization strategies and assess their ability to produce perfusable and functional vasculature that can be integrated with the host tissue.

Tissue-engineered skeletal muscle has the promise to be a tool for studying physiology, screening muscle-active drugs, and clinical replacement of damaged muscle. To maximize the potential benefits of engineered muscle, it is important to understand the factors required for tissue formation and how these affect muscle function. In this review, we evaluate how biomaterials, cell source, media components, and bioreactor interventions impact muscle function and phenotype.

Purpose: No cure is available for repair of damaged cartilage. Once damaged, cartilage will continue to degenerate, resulting in immobile and painful joints. Treatments are limited to symptom relief, while tissue engineering approaches fail to produce cartilage comparable to native articular cartilage in terms of strength and modulus. In this project, we investigated the use of self-assembling proteins as scaffold material for cartilage tissue engineering. These so-called amy-loid networks consist of amyloid fibrils forming physical cross-links. The fibrils self-assemble from proteins by forming inter-protein B-sheets. Amyloid networks resemble the extracellular matrix of cartilage since the strength and Young’s modulus of the fibrils is comparable to those of collagen and the networks are hydrogels. We therefore hypothesized that amyloid networks can be used as scaffold material for cartilage tissue engineering.

Cochleostomy or round window enlargement techniques for cochlear implant electrode insertion result in more abnormal tissue formation in the basal cochlea and are more apt to produce endolymphatic hydrops than round window electrode insertion.Twelve temporal bones from implanted patients were examined under light microscopy and reconstructed with 3-dimensional reconstruction software to determine cochlear damage and volume of neo-ossification and fibrosis after electrode insertion. Amount of new tissue was compared between 3 groups of bones: insertion through the round window (RW), after enlarging the RW (RWE) and cochleostomy (Cochl). The probable role of the electrode was evaluated in each case with hydrops.More initial damage occurred in the Cochl and RWE groups than in the RW group, and the difference was significant between RWE and RW in cochlear segment I (p0.026). The volume of new bone in Segment I differed significantly between groups (p0.012) and was greater in the RWE group than in either the Cochl or RW groups (post hoc p's0.035 and 0.019, respectively). Hydrops was seen in 5 cases, all in the Cochl and RWE groups. Blockage of the duct was because of new tissue formation in 4 of the 5 hydrops cases.With the electrodes in this series, implantation through the RW minimized initial intracochlear trauma and subsequent new tissue formation, whereas the RW extension technique used at the time of these implantations produced the greatest damage. Future studies may clarify whether today's techniques and electrodes will produce these same patterns of damage.