Progress in Organ Bioprinting for Regenerative Medicine

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

Abstract3D bioprinting is the most popular additive manufacturing method, in which solid objects are constructed by depositing several layers in sequence for the fabrication of biostructures. Bioprinted structures, like tissues, organs, and Organ-on-chip, in 3D, are now widely used to study and understand the functions of the human body. The 3D bioprinted structures are closely similar to naturally occurring biologics systems, and studies performed on 3D biostructures can be more biologically relevant than in vitro studies conducted in 2D. 3D bioprinting has advanced over the years and is commonly used in tissue engineering and regenerative medicine. The fabrication of biomaterials like cells, tissues, and organs using 3D bioprinting is becoming an alternative and favorable tissue and organ transplantation approach. Bioprinting is a relatively novel method and holds great promise but has several challenges and limitations. To this end, this chapter summarizes the concept of 3D bioprinting, bioinks and their classification, different methods of bioprinting, and their applications in areas of health, pharmaceutical science, and biomedical engineering. The chapter also highlights the challenges associated with the clinical utilization of 3D bioprinting. 3D bioprinting and its applications in personalized medicine and tissue bioengineering are continuously growing. In the future, this technology could provide advanced tools to the researchers to develop targeted treatment and improve patient outcomes.Keywords3D bioprintingTissue engineeringRegenerative medicineBioinksPharmaceuticalsMedical devicesOrgan-on-chip

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.

Bioprinting for stem cell research

From Tissue Engineering to Organ Engineering

Tissue engineering offers immense potential for addressing the unmet needs in repairing tissue damage and organ failure. Vascularization, the development of intricate blood vessel networks, is crucial for the survival and functions of engineered tissues. Nevertheless, the persistent challenge of ensuring an ample nutrient supply within implanted tissues remains, primarily due to the inadequate formation of blood vessels. This issue underscores the vital role of the human vascular system in sustaining cellular functions, facilitating nutrient exchange, and removing metabolic waste products. In response to this challenge, new approaches have been explored. Microfluidic devices, emulating natural blood vessels, serve as valuable tools for investigating angiogenesis and allowing the formation of microvascular networks. In parallel, bioprinting technologies enable precise placement of cells and biomaterials, culminating in vascular structures that closely resemble the native vessels. To this end, the synergy of microfluidics and bioprinting has further opened up exciting possibilities in vascularization, encompassing innovations such as microfluidic bioprinting. These advancements hold great promise in regenerative medicine, facilitating the creation of functional tissues for applications ranging from transplantation to disease modeling and drug testing. This review explores the potentially transformative impact of microfluidic and bioprinting technologies on vascularization strategies within the scope of tissue engineering.

Tissue engineering and regenerative medicine (TERM) as an emerging field is a multidisciplinary science and combines basic sciences such as biomaterials science, biology, genetics and medical sciences to achieve functional TERM-based products to regenerate or replace damaged or diseased tissues or organs. Probiotics are useful microorganisms which have multiple effective functions on human health. They have some immunomodulatory and biocompatibility effects and improve wound healing. In this article, we describe the latest findings on probiotics and their pro-healing properties on various body systems that are useable in regenerative medicine. Therefore, this review presents a new perspective on the therapeutic potential of probiotics for TERM.

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.

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.

Cell-instructive biomaterials are an essential component in tissue engineering and regenerative medicine. In the past three decades since the term “Tissue Engineering” was coined, researchers have made significant progress towards regenerating disease or damage tissues and organs by combining innovations in biomaterials, signaling molecules and cell therapies. However, challenges persist including limitations in properties of cell-instructive biomaterials, lack of advanced manufacturing technologies for precise spatiotemporal control of key players in tissue engineering, and hurdles in clinical translation and regulatory process. In this perspective article, we briefly review the current state of the field including the evolution in our understanding of the role biomaterial mechanics and scaffolding architecture, development of self-healing and modular biomaterials, and progress in advanced manufacturing technologies such as 3D bioprinting. In addition, we discuss about how innovation in research technologies including multi-omics and spatial biology, and advanced imaging modalities may pave the way for enhancing our understanding about cell-biomaterial interactions. Finally, we present our perspective as early career clinicians and researchers on the key role and potential impact that clinician-scientists can generate in the development, validation, clinical translation and adoption of the next-generation of cell-instructive biomaterials for application in engineering tissues and organs to impact human health.

Polysaccharide hydrogels, which can mimic the natural extracellular matrix and possess appealing physicochemical and biological characteristics, have emerged as significant bioinks for 3D bioprinting. They are highly promising for applications in tissue engineering and regenerative medicine because of their ability to enhance cell adhesion, proliferation, and differentiation in a manner akin to the natural cellular environment. This review comprehensively examines the fabrication methods, characteristics, and applications of polysaccharide hydrogel-driven 3D bioprinting, underscoring its potential in tissue engineering, drug delivery, and regenerative medicine. To contribute pertinent knowledge for future research in this field, this review critically examines key aspects, including the chemistry of carbohydrates, manufacturing techniques, formulation of bioinks, and characterization of polysaccharide-based hydrogels. Furthermore, this review explores the primary advancements and applications of 3D-printed polysaccharide hydrogels, encompassing drug delivery systems with controlled release kinetics and targeted therapy, along with tissue-engineered constructs for bone, cartilage, skin, and vascular regeneration. The use of these 3D bioprinted hydrogels in innovative research fields, including disease modeling and drug screening, is also addressed. Despite notable progress, challenges, including modulating the chemistry and properties of polysaccharides, enhancing bioink printability and mechanical properties, and achieving long-term in vivo stability, have been highlighted.

Chapter 12 - Impacts of nanotechnology in tissue engineering

The role of the cardiac extracellular matrix (cECM) in providing biophysical and biochemical cues to the cells housed within during disease and development has become increasingly apparent. These signals have been shown to influence many fundamental cardiac cell behaviors including contractility, proliferation, migration, and differentiation. Consequently, alterations to cell phenotype result in directed remodeling of the cECM. This bidirectional communication means that the cECM can be envisioned as a medium for information storage. As a result, the reprogramming of the cECM is increasingly being employed in tissue engineering and regenerativemedicine as a method with which to treat disease. In this chapter, an overview of the composition and structure of the cECM as well as its role in cardiac development and disease will be provided. Additionally, therapeutic modulation of cECM for cardiac regeneration as well as bottom-up and top-down approaches to ECM-based cardiac tissue engineering is discussed. Finally, lingering questions regarding the role of cECM in tissue engineering and regenerative medicine are offered as a catalyst for future research.

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

The Tissue Engineering and Regenerative Medicine International Society-Asia Pacific (TERMIS-AP) annual meeting was held in Sydney, Australia from 15-17 September 2010 and highlighted the latest developments in tissue engineering and regenerative medicine in the Asia-Pacific region. Several of the plenary lectures focused on the vascularization of tissue engineering constructs, an issue that is critical for the success of larger tissue engineered constructs and was central to the meeting overall. In addition, a wide range of research also presented developments in tissue engineering for a range of body tissues (including cardiac, neural, bone, cartilage, tendon, skeletal muscle and skin), as well as advances in technologies (high-throughput screening and microfluidics). Looking more broadly, the meeting incorporated developments covering the spectrum of fundamental research through to clinical studies, with discussions on how best to direct the scientific advances being made into realistic therapies that could be made widely available in the future. Overall, the meeting highlighted the promise of early strategies, which are now showing promising results in clinical trials, and the development of a strong foundation of research from which future therapies will no doubt be developed.