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Regenerative medicine is a promising new area of research that offers potential to treat diseased and injured tissue. In particular, the development of new biomaterial-based approaches shows promise for the treatment of challenging bone and cartilage injuries. Recent trends have focused on the development of biofunctional materials that have bioactive properties and are capable of supporting and promoting new tissue formation during the tissue repair process. This article discusses current biomaterial-based approaches for bone and cartilage repair and highlights emerging material functionalization methodologies including surface modification, growth factor delivery, cell-seeding strategies and gene therapy.

Synthetic protocells are rudimentary origin-of-life versions of natural cell counterparts. Protocells are widely engineered to advance efforts and useful accepted outcomes in synthetic biology , soft matter chemistry and bioinspired materials chemistry. Protocells in collective symbiosis generate synthetic proto-tissues that display unprecedented autonomy and yield advanced materials with desirable life-like features for smart multi-drug delivery, micro bioreactors , renewable fuel production, environmental clean-up, and medicine. Current levels of protocell and proto-tissue functionality and adaptivity are just sufficient to apply them in tissue engineering and regenerative medicine , where they animate biomaterials and increase therapeutic cell productivity. As of now, structural biomaterials for tissue engineering lack the properties of living biomaterials such as self-repair, stochasticity, cell synergy and the sequencing of molecular and cellular events. Future protocell-based biomaterials provide these core properties of living organisms, but excluding evolution. Most importantly, protocells are programmable for a broad array of cell functions and behaviors and collectively in consortia are tunable for multivariate functions. Inspired by upcoming designs of smart protocells, we review their developmental background and cover the most recently reported developments in this promising field of synthetic proto-biology. Our emphasis is on manufacturing proto-tissues for tissue engineering of organoids , stem cell niches and reprogramming and tissue formation through stages of embryonic development . We also highlight the exciting reported developments arising from fusing living cells and tissues, in a valuable hybrid symbiosis, with synthetic counterparts to bring about novel functions, and living tissue products for a new synthetic tissue engineering discipline.

In Ayurvedic perspectives in integrative healthcare, dhatu structure, by-products and disorders involve dhatu siddanta, which is the theory of tissue formation, the seven dhatus, ojas and srotamsi in dhatu tissue. The dhatu tissue are affected health regulated according to health, acute and chronic disorders which present qualitative and quantitative changes.

Multilayer systems capable of simultaneous dual tissue formation are crucial for regeneration of the osteochondral (OC) unit. Despite the tremendous effort in the field there is still no widely accepted system that stands out in terms of superior OC regeneration. Herein, we developed bilayered hydrogel composites (BHC) combining two structurally stratified layers fabricated from naturally derived and synthetic polymers, gellan-gum (GG) and hydroxyapatite (HAp), respectively. Two formulations were made from either low acyl GG (LAGG) alone or in combination with high acyl GG (HAGG) for the cartilage-like layer. Four bone-like layers were made of LAGG incorporating different ratios of hydroxyapatite (HAp). BHC were assembled in one single construct resulting in eight distinct bilayered constructs. Architectural observations by stereomicroscope and micro-CT (μ-CT) demonstrated a connected stratified structure with good ceramic dispersion within the bone-like layer. Swelling and degradation tests as well mechanical analyse showed a stable viscoelastic construct under dynamic forces. In-vitro studies by encapsulating rabbit's chondrocytes and osteoblasts in the respective layers showed the cytocompatibility of the BHC. Further studies comprising subcutaneous implantation in mice displayed a weak immune response after four weeks. OC orthotopic defects in the rabbit's knee were created and injected with the acellular BHC. OC tissue was regenerated four weeks after implantation as confirmed by cartilaginous and bony tissue formation assessed by histologic staining and μ-CT analysis. The successful fabrication of injectable BHC and their in-vitro and in-vivo performance may be seen as advanced engineered platforms to treat the challenging OC defects., This material is based on works supported by the Portuguese Foundation for Science and Technology (FCT) under the OsteoCart project (PTDC/CTM-BPC/115977/2009) and for the M-ERA-NET/0001/2014 project. The authors are grateful to Teresa Oliveira for the assistance with histological studies. DR Pereira acknowledges the FCT for the individual grant (SFRH/BD/81356/2011) and JM Oliveira also thanks the FCT for the funds provided under the program Investigator FTC 2012 and 2015 (IF/00423/2012 and IF/01285/2015)., info:eu-repo/semantics/publishedVersion

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.

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.

Tissue engineering has been used to regenerate various tissues and organs, and some engineered products have been commercialized and used for clinical applications. Porous scaffolds play an important role as a temporary support for the implanted cells to support their assembly and control their function to guide formation of functional tissues and organs. The characteristics of scaffolds such as pore structure, surface, and mechanical properties determine the quality of engineered tissues. Design of the porous structure and the preparation of optimized scaffolds has been a key objective of tissue engineering to enhance their performance and facilitate tissue formation. Many methods have been developed to prepare various porous scaffolds of biodegradable synthetic polymers, naturally derived polymers, and their hybrids to meet the needs of the scaffolds. This chapter summarizes biodegradable polymer-based porous scaffolds and some preparation methods.

The skin is a fundamental barrier that interfaces with the environment, constituting the first line of defense from physical, chemical, and biological attacks. To counteract the insults multiple and complex pathway systems have evolved and been built up in the skin. Skin injuries, such as wounds, induce a highly dynamic repair program starting from inflammation and moving to tissue formation and maturation, where specific cell–cell and cell–matrix interactions, cytokines, and growth factors, in collaboration, aim to recover its integrity and homeostasis. In this context the inflammatory response plays a key role in directing the outcome of the wound healing response that is otherwise unbalanced in the chronic repair process, especially in patients with diabetes. The management of chronic wounds will be discussed, trying to ameliorate the comprehension of the relationships among the cellular types occurring in the healing process.

The use of bioceramic scaffolds for hard tissue repair, augmentation, and substitution is continuously increasing in many dental and medical applications. It is well established that the in vivo biodegradation and bioresorption of ceramic scaffolds at rates appropriate to tissue regeneration play a vital role in enabling new tissue formation. Furthermore, the various ionic by-products of biodegradation of scaffolding materials result in the enrichment of the microenvironment, which can affect, positively or negatively, the proliferation and activity of cells. Therefore, the factors affecting degradation or the extent of dissolution of the scaffolding materials are important. The aim of this chapter is to discuss the processes of biodegradation or bioresorption of bioceramic scaffolds in terms of the physical, chemical, and biocompatibility that occur when in contact with simulated body fluids, cells, or living tissue, focusing on the applied characterization techniques.

This chapter discusses current advancements in cartilage tissue regeneration with emphasis on the use of hydrogel-based nanocomposites for improved cartilage regeneration. Through the course of this chapter, we will begin with an introduction to cartilage regeneration focusing on material characteristics necessary for successful tissue regeneration. In addition, we will explore and evaluate varying scaffold fabrication strategies as well as the incorporation of biologics for in vitro evaluation and enhanced tissue formation. Lastly, a concise summary and future direction of cartilage tissue regeneration will be discussed with respect to clinical applications of hydrogel-based therapies.

The main aim of tissue engineering is to improve or replace biological functions of all or any of the four basic tissue types. It often involves the creation of appropriate scaffolds that promote tissue formation. These scaffolds can provide pathways for repair and regeneration. It is therefore vitally important that we fully understand the intimate web of cellular interactions in these constructs if we hope to develop practical devices for functional aids to tissue repair. We have at our disposal a wide variety of stereological tools that can help to provide access to the three-dimensional spatial framework of the biomaterial tissue interface. These methods can enable objective quantitation of structure–function relations. Adequate sampling is central to the stereological approach. This chapter will highlight useful approaches to quantify functionally relevant tissue properties. A key question is what to measure? The stereological approach makes estimates of parameters of geometrical structures. The parameters include volume, surface area, number, thickness, and spacing. In stereology, the nature or function of the structure is not important. The application of these methods should allow us to better understand host tissue behavior. These methods permit quantitation of the scaffold itself as well as local cell and tissue responses. It is an ideal approach to study the scaffold itself as well as the myriad array of cell and tissue responses. Holes can also be considered as structures. The application of stereological methods has been providing a spatial framework on which to lay physiological and molecular information in neuroscience, reproductive biology, and cancer cell biology. In this chapter, we explore the usefulness of this approach in tissue engineering. The wider use of these methods should allow us to better understand host tissue behavior and allow us to develop more functionally relevant tissue engineering solutions.

Extrusion bioprinting has exciting prospects in fabricating organized tissue constructs by simultaneous dispensing of cells and matrix materials to repair or replace damaged or diseased tissues and organs. The exhilarating capability of this technique is to generate constructs with spatial variations of cells along multiple axes with high geometric complexity. A variety of bioprinters based on extrusion principle have been developed around the world and many are even commercialized. These computer-controlled technologies to design and fabricate tissues will enhance our understanding of the governing factors of tissue formation and function. Moreover, it will provide a valuable tool for several emerging technologies including tissue engineering. In this chapter, we discuss the rationale of extrusion-based bioprinting for fabrication of tissue constructs. Current strategies of building tissue constructs are discussed; in particular, their merits and demerits and the requirements to move the current concepts to practical application are highlighted.

Tissue engineering for reconstruction/regeneration of airways can be regarded as a potential approach for the treatment of severe pathologies that can dramatically impair the correct function of the involved organs. Total or partial transplantation can be the surgical solution for these occurrences, but several limitations are generally associated with this option, as it is dependent on donor shortage and host response to the implanted material. A viable and ready-to-use substitute, able to promote novel tissue formation, would therefore be the desirable scaffold to deal with. Synthetic materials can represent an alternative for this task. Obviously, several drawbacks can be listed to their use, but they can be potentially tailored and modified to minimally reduce the risk of a negative outcome. Herein, the investigated synthetic materials tested so far in order to develop a viable tissue-engineered tracheal scaffold are presented and discussed.

Patients with mixed-type femoroacetabular impingement syndrome often have concomitant chondrolabral pathology in addition to the characteristic cam and pincer lesions. Unfortunately, these patients are typically young, and the pathology is localized to the weight-bearing dome of the acetabulum. Complete preoperative characterization of labral and cartilage lesions is often not possible even with advanced imaging techniques, and the full extent of the injury may not be appreciated without direct arthroscopic visualization. Thus management decisions regarding intra-articular pathology may not be possible until the time of surgery. Often, the cartilage and labral pathology in these young patients is part of a contiguous complex of tissue that separates from the underlying subchondral bone. We present an arthroscopic management technique for young patients with this pattern of injury. This includes limited debridement of loose labral and chondral tissue, labral repair to restore the suction-seal effect, microfracture to promote reparative tissue formation, and takedown of the underlying pathoanatomic cam and pincer lesions.

Three-dimensional (3D) scaffolds serve as temporary substrates for supporting and guiding tissue formation in various in vitro and in vivo tissue regeneration settings. Recent years have seen the emergence of scaffolds designed to explicitly control various aspects of the tissue formation process. Spatiotemporal control of scaffold biochemical and physical properties has been investigated via the incorporation of fundamental molecular and cellular bio-mechanisms into scaffolds. As living cells and tissues are highly complex systems, a central theme in designing tissue-engineering scaffolds is understanding how scaffold structures, properties and functions are correlated. In this chapter, fundamental scaffold design variables (i.e., mass transport, mechanics, electrical conductivity, surface chemistry and topology) are decoupled and analyzed in terms of how they have been engineered to control cell behavior through different constituent biomaterials and architectural structures. Approaches for temporal and spatial control are further described to illustrate principles that may guide integrated rational design of 3D scaffolds.

Bioreactors allow for engineering complex three-dimensional tissues in vitro as well as understanding and controlling tissue assembly and function on a cellular level. There are numerous designs, configurations, and conditions that have been applied for cell and tissue culture of liver, heart, bone, cartilage, ligaments, blood vessels and other tissues. Computational fluid dynamics as well as other monitoring and sensing technologies can further optimize the mechanical, electrical and chemical conditions used in bioreactors. This chapter is a brief summary of technologies and conditions tested in bioreactor systems for cell infiltration and tissue formation, as well as a review of critical shortcomings and future developments that would allow for development of clinically relevant tissues.

Polymer patterning is a versatile approach that can be used to manipulate, guide, and explore biological processes. Applications of polymer patterning covered in this chapter include techniques used to investigate DNA replication, the use of protein and gene arrays to characterize cell activity, the use of self-assembly to control cell patterning and tissue formation, the study of response of cells to various chemical and topographical cues, and the high-throughput investigation of cell response to molecules and materials.

Modification of the surface chemistry of bone replacement materials in order to provide enhanced cell attachment, growth and tissue formation can be achieved via various processes which in turn, are not detrimental to the mechanical properties of the bulk material. The most common involve the deposition of calcium phosphates onto the implant surface which is able to direct cells to an osteogenic phenotype. The most recent techniques of depositing calcium phosphate coatings are discussed in this chapter, illustrating their effects on the mechanical and biological performance of the coated substrates and their potential for future clinical applications.

Organ-printing techniques offer the potential to produce living 3D tissue constructs to repair or replace damaged or diseased human tissues and organs. Using these techniques, spatial variations along multiple axes with high geometric complexity can be obtained. The level of control offered by these technologies to develop printed tissues will allow tissue engineers to better study factors that modulate tissue formation and function, and provide a valuable tool to study the effect of anatomy on graft performance. In this chapter, we discuss the history behind substrate patterning, and cell and organ printing, and the rationale for developing organ-printing techniques with respect to the limitations of current clinical tissue engineering strategies in effectively repairing damaged tissues. We discuss current two-dimensional and three-dimensional strategies for assembling cells as well as the necessary support materials such as hydrogels, bioinks, and natural and synthetic polymers adopted for organ-printing research. Furthermore, given the current state-of-the-art in organ-printing technologies, we discuss some of their limitations and provide recommendations for future developments in this rapidly growing field.

In the last three decades, tissue engineering has emerged as a new discipline with the aim of addressing serious clinical cases where the spontaneous repair of damaged tissue is impaired. Bone tissue engineering is one of the most investigated areas of application and a large body of data is now available that sheds light on the ideal features of a bone tissue engineering construct. Materials scientists are now able to synthesise biomimetic and bioresponsive biomaterials that fulfil the main requirements for tissue formation in vitro or in vivo. Biodegradable/bioresorbable polymers, ceramics and composites have been developed which can act as substrates for the adhesion of cells and for the deposition of the calcium phosphate mineral phase of the bony tissues. When engineered into three-dimensional (3D) scaffolds able to host cells (progenitor or differentiated) and bioactive molecules (growth factors, genes and drugs), these biomaterials can constitute an ideal environment to foster the formation of new tissue and to integrate it into the host environment. Although preliminary clinical studies have shown the great potential of bone tissue engineering, the constructs employed still lack an integrated approach where clinical needs are met by a careful design of the construct in all its components and growing conditions. These unmet clinical needs require a coordinated response by scientists, industrialists and policy makers.

The mechanical interaction between a cell and its substrate can affect and control cell behavior and function. As a cell adheres to and moves across a substrate, it exerts traction forces. Several laboratories have put forward methods to investigate and quantify these traction forces. Here, we review the various approaches developed to measure traction forces and some of the most significant findings resulting from the application of these techniques. Additionally, we discuss recent results from our laboratory quantifying traction forces exerted by endothelial cells, to better understand the process of two-dimensional tissue formation using angiogenesis as a model. As the interaction between a cell and its substrate is crucial for transmission of mechanical cues from the cell to the substrate and from the extracellular milieu to the cell, further investigation into cellular traction forces will continue to elucidate the role of mechanical forces in cell function and tissue formation.

This work is concerned with improving nonwoven scaffold design for the tissue engineering of the anterior cruciate ligament. When designing a scaffold two important design criteria to consider are scaffold's internal structure and biocompatibility, both of which are addressed in this paper. The role of a scaffold is to provide a framework for cells to attach, proliferate and secrete extra cellular matrix. The scaffold also acts as a template, directing the growth of cells and newly formed tissue. It is the scaffold's internal structure, together with polymer surface chemistry and morphology, which directly influence the cellular activities that lead to tissue formation. With regard to scaffold's internal structure, structural parameters are discussed in relation to specific scaffold function; for example the effect of scaffold pore-size on cell proliferation, migration and nutrient supply. Another structural factor discussed is the role of fibre orientation as a means of guiding and organising new tissue growth. With the aim of creating a scaffold of optimum design, for the tissue engineering of the anterior cruciate ligament, nonwoven scaffolds of differing structure have been constructed. In order to understand the relationship between manufacturing method and scaffold structure characterisation techniques have been employed to analyse the structural parameters of these scaffolds. Obtained scaffold structural properties are discussed in relation to manufacturing method. Regarding the second scaffold criteria biocompatibility tests have been conducted by the authors on a range of generic fibre types. The results of these tests are provided in the form of cell attachment, with reference to fibre morphology.

Publisher Summary This chapter describes models of angiogenesis and the blood–brain barrier (BBB). Angiogenesis, the formation of new blood vessels, is a requisite developmental event in organ and tissue formation. In the embryonic brain, endothelial cells that comprise the vasculature proliferate at a moderate pace and essentially cease division by day 20–25 in the rat. In the mature brain, the cerebral endothelia are stable, and their turnover rate is extremely low. Angiogenesis in adult brain is an event that occurs only under conditions of an injury or pathological event. Concurrent with new endothelial growth and vessel formation following a pathological occurrence is a breakdown of the BBB. There are many different conditions, both clinical and experimental, in which BBB breakdown occurs. In several experimental paradigms, endothelial cell division can be documented in mature rat brain. The experiments that are described in this chapter involve the implantation of tissues and cells into the brain and the subsequent examination of vascular growth and changes in the BBB. The chapter, highlights techniques for localization of proliferating vasculature (angiogenesis). It also discusses strategies for determining temporal sequence and source of neovascularization in neural transplants.

Publisher Summary This chapter discusses the formation of cross-species nerve connections in mouse hippocampal xenografts placed in the rat brain. The formation of nerve connections between the mouse fascia dentata and the host rat brain appears to be regulated by the same factors, which determines the exchange of host-graft connections in rat allograft studies. The chapter discusses conclusions on the basis of experimental findings: (1) surviving, intracerebral xenografts of mouse fascia dentata and hippocampus are organotypically organized and exchange nerve connections with the host rat brain to the same extent and according to the same principles as rat allografts; (2) complete structural integration in terms of merging of cell and neuropil layers and migration of host rat dentate granule cells into the mouse dentate xenografts is common after grafting to newborn recipients; and (3) the expression of species-specific cholecystokinin (CCK) immunoreactivity in mouse mossy fiber terminals with ingrowth into the host rat hippocampus provides a model for further studies of the developmental and functional interactions between defined groups of neurons.