Chapter 12 - Impacts of nanotechnology in tissue engineering

Recently, tissue engineering and regenerative medicine, especially bone tissue engineering and regenerative medicine have developed rapidly. Bone tissue engineering is a complicated and dynamic bone remodeling process that starts with recruitment and migration of osteoblasts and then regulates their proliferation, differentiation, and mineralization. Scaffold is typically biodegradable material that plays a crucial role as one of the three elements of bone tissue engineering and regenerative medicine. Bone scaffold provides the mechanical support during reformation and repair of damaged or diseased bone. For more than a decade, a large amount of research work has been carried out on the designing of scaffolds, processing techniques, performance assessment, and medical application. Significant progress has been made toward scaffold materials for structural support for desired osteogenesis and angiogenesis abilities. To date, depending on the advanced technologies, the bioresorbable scaffolds possess controlled porosity and high mechanical properties are possible used as bone scaffold. Natural bone has delicate architectural structure that spans nanoscale to macroscopic dimensions, which determine the unique mechanical properties of bone. The hierarchical structure of natural bone can be defined as a nanocomposite consisting of inorganic nanocrystalline hydroxyapatite (HA), organic components (mostly are collagens) and water. The outside proteins assemble together to form an extracellular matrix (ECM) with nanostructured which influences the adhesion, proliferation, differentiation, and mineralization of several cell types, such as bone lining cell, mesenchymal stem cells, osteoblasts, osteocytes, and osteoclasts. To better mimic the nanostructure in natural ECM, many research groups over the past decade developed nano-based scaffolds (nanotubes, nanofibers, nanoparticles, and hydrogel) to resemble the ECM for promising candidates in replacing defective tissues. The high biomimetic properties and excellent mechanical features of nano-based scaffolds plays a vital role in stimulating cell adhesion and proliferation, as well as directing bone tissue formation through mimetic the nanometer dimension of natural bone tissue. Besides, mechanical properties are key factors for bone regeneration and bone local function. Nowadays, a large number of research groups have tried to manipulate the mechanical properties of scaffolds through designing the different nanosturctures, including nanofiber, nanoparticle, polymer matrices to mimic the nanocomposite structure of natural bone. These materials have highly stiffness, strength, and toughness properties that are promising in bone tissue engineering. Nanobiomaterials, especially inorganic nanobiomaterials, have excellent mechanical properties and biocompatibility, and are ideal for the preparation of scaffold materials for bone tissue engineering and regenerative medicine, showing a broad application prospect. In this article, we systematically review the application of inorganic nanomaterials, including hydroxyapatite, silicon-based nanomaterials, carbon-containing nanomaterials and several metal nanomaterials in bone tissue engineering and regenerative medicine. Although nanotechnology represents a major frontier with potential to significantly advance the field of bone tissue engineering, the application in the clinical regenerative engineering has limited. Currently, there are several limitations in regenerative strategies, including low efficient cellular proliferation, differentiation and mineralization, insufficient mechanical strength of scaffolds, and limited production of growth factors necessary for efficient osteogenesis. Therefore, there are still some issues on the nano-based scaffold should be cleared: (1) The interaction of nano-based scaffold and bioactive molecules, growth factors, and genetic material, (2) the biocomptibility, cytotoxicity, and biodegradation of nano-based scaffold, and (3) nano-based scaffold mechanical stability, cellular survival, and molecular mechanism of inducing bone formation. As the development of nanotechnology, ultimate translation to the clinical application may allow for improved therapeutic outcomes in patients with large bone deficits and osteodegenerative diseases.

Gelatin is a biocompatible, biodegradable and fully absorbable biopolymer. These properties have attracted significant interests in the use of gelatin for a wide range of tissue engineering applications. This chapter covers the studies that focused on using gelatin-based biomaterials for cardiovascular, bone, hepatic, skin and corneal tissue engineering. It discusses the application of gelatin for wound healing and injectable fillers. Stem cells hold great a potential in tissue regeneration applications due to their self renewal capacity and differentiation toward specialized cell types. The chapter discusses various strategies that have been utilized to modulate stem cell behavior by altering the biochemical and biophysical properties of gelatin. Gelatin-based delivery systems have found success in gene and siRNA delivery, to induce the expression of therapeutic proteins or trigger gene silencing, respectively. Overall, gelatin based drug delivery systems have demonstrated great utility and versatility in many biomedical applications.

Tissue engineering has tremendous potential for the treatment of a wide range of medical conditions. In combination with this, the developments in the fields of embryonic stem cells (ES) and adult stem cells are leading to a whole new generation of therapies. However, for any treatment to be successful, a number of key issues must be addressed; in particular the choice of cell and scaffold types used and the methods required to overcome immune rejection of any transplant. The 1-day EuroSciCon meeting, at the MI Centre in London, UK, on November 17, 2006, covered the recent advances in the fields of tissue engineering and regenerative medicine. Entitled ‘Tissue Engineering Today, Not Tomorrow’, the meeting drew presenters from throughout Europe and as far afield as Japan. It focused on the key areas of development in stem cell differentiation, scaffold development and immune modulation, each with a clinical setting or scenario in mind. The conference was opened by Dame Julia Polak (Imperial college, London, UK), who gave an interesting overview of the processes involved in developing tissue engineering from the laboratory into the clinic. Specific examples were given for the importance of biochemical and physical microenvironments on ES cell differentiation and how gene overexpression of osterix can induce bone formation. The use of bioglass for bone regeneration and collagen–polyglycolic acid composite scaffolds for bladder tissue engineering were also given. In conclusion, Dame Polak discussed how the fields of stem cells, tissue engineering, gene therapy, nanotechnology and regenerative medicine are all converging for clinical application to save lives. This gave a good introduction to the themes of the remaining talks.

Biomaterial-based 3D bioprinting strategy for orthopedic tissue engineering.

Cardiovascular Tissue Engineering

From Tissue Engineering to Organ Engineering

Since its emergence nearly 30 years ago with the goal of fabricating replacement human tissues or assisting the body in repairing itself, several advances have been made in the fields of tissue engineering and regenerative medicine. The assembly of living cells into tissues is akin to the scale‐up operation of a chemical or biochemical process with several modules or units affecting the final product. The major modules or units in tissue engineering and regenerative medicine are cells, biodegradable scaffolds, bioreactors, and biomolecules. Each module is analogous to unit operations, where individual units must come together to successfully design engineered tissues for therapeutic and drug discovery applications. Basic principles of biological sciences, chemical engineering, materials chemistry, and polymer processing are frequently employed. More specifically, knowledge about viscous fluid flow, mass transfer, and reaction engineering is essential in tissue engineering. In this review article, we present the nexus between chemical engineering and tissue engineering for the rational design of engineered tissues or injectable cell‐laden hydrogel systems.

Over the past few decades, the engineering of helical, spring, curled, and hierarchically structured nano/microfibers has attracted considerable attention due to their unique characteristics and potential applications in tissue engineering and various industrial fields. Understanding the parameters and processes involved in the fabrication of these fibers is essential. This comprehensive review outlines recent advancements in research on helical nano/microfibers, focusing on processing techniques, fiber structure, and property characterization, and their applications in fields such as tissue engineering and regenerative medicine. The study also investigates the mechanical and hydrodynamic parameters that influence the fabrication of helical fibers using contemporary techniques. It highlights that helical structures form when electric and elastic forces are balanced due to non-uniform electric fields. The coaxial electrospinning technique, along with the use of polymers with varying elastic and conductive properties, plays a crucial role in producing these structures. The distinctive properties of helical nanofibers, such as their mechanical strength, high porosity, biocompatibility, and ability to promote cellular activities, make them promising candidates for developing scaffolds in bone tissue engineering.

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.

Nanocomposite bioinks for 3D bioprinting

Guided bone regeneration (GBR) is a promising technique in bone tissue engineering that aims to replace lost or injured bone using resorbable scaffolds. The promotion of osteoblast adhesion, migration, and proliferation is greatly aided by GBR materials, and surface changes are critical in imitating the natural bone structure to improve cellular responses. Moreover, the interactions between bioresponsive scaffolds, growth factors (GFs), immune cells, and stromal progenitor cells are essential in promoting bone regeneration. This literature review comprehensively discusses various aspects of resorbable scaffolds in bone tissue engineering, encompassing scaffold design, materials, fabrication techniques, and advanced manufacturing methods, including three-dimensional printing. In addition, this review explores surface modifications to replicate native bone structures and their impact on cellular responses. Moreover, the mechanisms of bone regeneration are described, providing information on how immune cells, GFs, and bioresponsive scaffolds orchestrate tissue healing. Practical applications in clinical settings are presented to underscore the importance of these principles in promoting tissue integration, healing, and regeneration. Furthermore, this literature review delves into emerging areas of metamaterials and artificial intelligence applications in tissue engineering and regenerative medicine. These interdisciplinary approaches hold immense promise for furthering bone tissue engineering and improving therapeutic outcomes, leading to enhanced patient well-being. The potential of combining material science, advanced manufacturing, and cellular biology is showcased as a pathway to advance bone tissue engineering, addressing a variety of clinical needs and challenges. By providing this comprehensive narrative, a detailed, up-to-date account of resorbable scaffolds' role in bone tissue engineering and their transformative potential is offered.

Recent research in the vaccine and immunotherapy fields has revealed that biomaterials have the ability to activate immune pathways, even in the absence of other immune‐stimulating signals. Intriguingly, new studies reveal these responses are influenced by the physicochemical properties of the material. Nearly all of this work has been done in the vaccine and immunotherapy fields, but there is tremendous opportunity to apply this same knowledge to tissue engineering and regenerative medicine. This review discusses recent findings that reveal how material properties—size, shape, chemical functionality—impact immune response, and links these changes to emerging opportunities in tissue engineering and regenerative medicine. We begin by discussing what has been learned from studies conducted in the contexts of vaccines and immunotherapies. Next, research is highlighted that elucidates the properties of materials that polarize innate immune cells, including macrophages and dendritic cells, toward either inflammatory or wound healing phenotypes. We also discuss recent studies demonstrating that scaffolds used in tissue engineering applications can influence cells of the adaptive immune system—B and T cell lymphocytes—to promote regenerative tissue microenvironments. Through greater study of the intrinsic immunogenic features of implantable materials and scaffolds, new translational opportunities will arise to better control tissue engineering and regenerative medicine applications.

Synergistic interplay between human MSCs and HUVECs in 3D spheroids laden in collagen/fibrin hydrogels for bone tissue engineering

Bio-printing is a trending technology in the field of tissue engineering and regenerative medicine, creating complex three-dimensional structures. The advancements in bio-printing, including the steps and materials used in bio-printers, have been highlighted. Various bio-printing techniques such as micro-extrusion, inkjet printing, and laser-based approaches are discussed. Moreover, the roles of biomaterials and their importance in bio-printing cannot be overstated. Characteristics such as cell viability, adhesion, differentiation, biodegradability, and biocompatibility are paramount in ensuring the success of bio-printed tissues. Additionally, the interdisciplinary nature of bio-printing research fosters collaborations between biologists, engineers, material scientists, and medical professionals. This synergy facilitates the development of innovative bio-printing technologies and accelerates their translation into clinical applications. Furthermore, the evolution of bio-printing technology is not only reshaping medical practice but also opening new frontiers in scientific exploration. By mimicking the complex architectures and functionalities of native tissues, bio-printed constructs serve as valuable tools for studying tissue development, disease mechanisms, and drug responses. The ability to recreate physiologically relevant microenvironments in vitro provides researchers with unprecedented insights into cellular behavior and tissue dynamics. The bio-printing represents a transformative approach in tissue engineering and regenerative medicine, offering unparalleled opportunities for tissue fabrication, disease modeling, and drug discovery. As research in this field continues to progress, we can anticipate even more remarkable breakthroughs that will revolutionize healthcare and biomedical research.

Tissue engineering and regenerative medicine have shown potential in the repair and regeneration of tissues and organs via the use of engineered biomaterials and scaffolds. However, current constructs face limitations in replicating the intricate native microenvironment and achieving optimal regenerative capacity and functional recovery. To address these challenges, the utilization of decellularized tissues and cell-derived extracellular matrix (ECM) has emerged as a promising approach. These biocompatible and bioactive biomaterials can be engineered into porous scaffolds and grafts that mimic the structural and compositional aspects of the native tissue or organ microenvironment, both in vitro and in vivo. Bioactive dECM materials provide a unique tissue-specific microenvironment that can regulate and guide cellular processes, thereby enhancing regenerative therapies. In this review, we explore the emerging frontiers of decellularized tissue-derived and cell-derived biomaterials and bio-inks in the field of tissue engineering and regenerative medicine. We discuss the need for further improvements in decellularization methods and techniques to retain structural, biological, and physicochemical characteristics of the dECM products in a way to mimic native tissues and organs. This article underscores the potential of dECM biomaterials to stimulate in situ tissue repair through chemotactic effects for the development of growth factor and cell-free tissue engineering strategies. The article also identifies the challenges and opportunities in developing sterilization and preservation methods applicable for decellularized biomaterials and grafts and their translation into clinical products.