Cellulose nanocrystals (CNCs) are a renewable nanosized raw material that is drawing a tremendous level of attention from the materials community. These rod-shaped nanocrystals that can be produced ...from a variety of highly available and renewable cellulose-rich sources are endowed with exceptional physicochemical properties which have promoted their intensive exploration as building blocks for the design of a broad range of new materials in the past few decades. However, only recently have these nanosized substrates been considered for bioapplications following the knowledge on their low toxicity and ecotoxicological risk. This Review provides an overview on the recent developments on CNC-based functional biomaterials with potential for tissue engineering (TE) applications, focusing on nanocomposites obtained through different processing technologies usually employed in the fabrication of TE scaffolds into various formats, namely, dense films and membranes, hierarchical three-dimensional (3D) porous constructs (micro/nanofibers mats, foams and sponges), and hydrogels. Finally, while highlighting the major achievements and potential of the reviewed work on cellulose nanocrystals, alternative applications for some of the developed materials are provided, and topics for future research to extend the use of CNCs-based materials in the scope of the TE field are identified.
Bone tissue engineering (BTE) is a rapidly growing field aiming to create a biofunctional tissue that can integrate and degrade in vivo to treat diseased or damaged tissue. It has become evident that ...scaffold fabrication techniques are very important in dictating the final structural, mechanical properties, and biological response of the implanted biomaterials. A comprehensive review of the current accomplishments on scaffold fabrication techniques, their structure, and function properties for BTE is provided herein. Different types of biomaterials ranging from inorganic biomaterials to natural and synthetic polymers and related composites for scaffold processing are presented. Emergent scaffolding techniques such as electrospinning, freeze‐drying, bioprinting, and decellularization are also discussed. Strategies to improve vascularization potential and immunomodulation, which is considered a grand challenge in BTE scaffolding, are also presented.
Bone tissue engineering aims to create biofunctional tissue, while scaffold fabrication techniques are rapidly evolving with higher spatial resolutions and hierarchical structural capabilities, enabling the possibility of tailoring the mechanical and biological response of implanted biomaterials. Herein, commentary on current structure/property/function relationships of biomaterials in bone tissue engineering and how these are influenced by the latest scaffold fabrication technologies are offered.
Tissue engineering and regenerative medicine has been providing exciting technologies for the development of functional substitutes aimed to repair and regenerate damaged tissues and organs. Inspired ...by the hierarchical nature of bone, nanostructured biomaterials are gaining a singular attention for tissue engineering, owing their ability to promote cell adhesion and proliferation, and hence new bone growth, compared with conventional microsized materials. Of particular interest are nanocomposites involving biopolymeric matrices and bioactive nanosized fillers. Biodegradability, high mechanical strength, and osteointegration and formation of ligamentous tissue are properties required for such materials. Biopolymers are advantageous due to their similarities with extracellular matrices, specific degradation rates, and good biological performance. By its turn, calcium phosphates possess favorable osteoconductivity, resorbability, and biocompatibility. Herein, an overview on the available natural polymer/calcium phosphate nanocomposite materials, their design, and properties is presented. Scaffolds, hydrogels, and fibers as biomimetic strategies for tissue engineering, and processing methodologies are described. The specific biological properties of the nanocomposites, as well as their interaction with cells, including the use of bioactive molecules, are highlighted. Nanocomposites in vivo studies using animal models are also reviewed and discussed.
Nanocomposite scaffolds combining biopolymers and calcium phosphate nanoparticles have a great potential in tissue engineering and regenerative medicine because of their ability to mimic the hierarchical structure and mechanical properties of bone tissue. They can be functionalized with cells and suitable biochemical signals, which promote tissue regeneration.
In the field of tissue engineering and regenerative medicine, hydrogels are used as biomaterials to support cell attachment and promote tissue regeneration due to their unique biomimetic ...characteristics. The use of natural-origin materials significantly influenced the origin and progress of the field due to their ability to mimic the native tissues' extracellular matrix and biocompatibility. However, the majority of these natural materials failed to provide satisfactory cues to guide cell differentiation toward the formation of new tissues. In addition, the integration of technological advances, such as 3D printing, microfluidics and nanotechnology, in tissue engineering has obsoleted the first generation of natural-origin hydrogels. During the last decade, a new generation of hydrogels has emerged to meet the specific tissue necessities, to be used with state-of-the-art techniques and to capitalize the intrinsic characteristics of natural-based materials. In this review, we briefly examine important hydrogel crosslinking mechanisms. Then, the latest developments in engineering natural-based hydrogels are investigated and major applications in the field of tissue engineering and regenerative medicine are highlighted. Finally, the current limitations, future challenges and opportunities in this field are discussed to encourage realistic developments for the clinical translation of tissue engineering strategies.
Stem cells have been long looked at as possible therapeutic vehicles for different health related problems. Among the different existing stem cell populations, Adipose- derived Stem Cells (ASCs) have ...been gathering attention in the last 10 years. When compared to other stem cells populations and sources, ASCs can be easily isolated while providing simultaneously higher yields upon the processing of adipose tissue. Similar to other stem cell populations, it was initially thought that the main potential of ASCs for regenerative medicine approaches was intimately related to their differentiation capability. Although this is true, there has been an increasing body of literature describing the trophic effects of ASCs on the protection, survival and differentiation of variety of endogenous cells/tissues. Moreover, they have also shown to possess an immunomodulatory character. This effect is closely related to the ASCs' secretome and the soluble factors found within it. Molecules such as hepatocyte growth factor (HGF), granulocyte and macrophage colony stimulating factors, interleukins (ILs) 6, 7, 8 and 11, tumor necrosis factor-alpha (TNF-alpha), vascular endothelial growth factor (VEGF), brain derived neurotrophic factor (BDNF), nerve growth factor (NGF), adipokines and others have been identified within the ASCs' secretome. Due to its importance regarding future applications for the field of regenerative medicine, we aim, in the present review, to make a comprehensive analysis of the literature relating to the ASCs' secretome and its relevance to the immune and central nervous system, vascularization and cardiac regeneration. The concluding section will highlight some of the major challenges that remain before ASCs can be used for future clinical applications.
Sulfation is a dynamic and complex posttranslational modification process. It can occur at various positions within the glycosaminoglycan (GAG) backbone and modulates extracellular signals such as ...cell-cell and cell-matrix interactions; different sulfation patterns have been identified for the same organs and cells during their development. Because of their high specificity in relation to function, GAG sulfation patterns are referred to as the sulfation code. This review explores the role of GAG sulfation in different biological processes at the cell, tissue, and organism levels. We address the connection between the sulfation patterns of GAGs and several physiological processes and discuss the misregulation of GAG sulfation and its involvement in several genetic and metabolic disorders. Finally, we present the therapeutic potential of GAGs and their synthetic mimics in the biomedical field.
The encapsulation of living mammalian cells within a semi-permeable hydrogel matrix is an attractive procedure for many biomedical and biotechnological applications, such as xenotransplantation, ...maintenance of stem cell phenotype and bioprinting of three-dimensional scaffolds for tissue engineering and regenerative medicine. In this review, we focus on naturally derived polymers that can form hydrogels under mild conditions and that are thus capable of entrapping cells within controlled volumes. Our emphasis will be on polysaccharides and proteins, including agarose, alginate, carrageenan, chitosan, gellan gum, hyaluronic acid, collagen, elastin, gelatin, fibrin and silk fibroin. We also discuss the technologies commonly employed to encapsulate cells in these hydrogels, with particular attention on microencapsulation.
The current available therapeutics face several challenges such as the development of ideal drug delivery systems towards the goal of personalized treatments for patients benefit. The application of ...light as an exogenous activation mechanism has shown promising outcomes, owning to the spatiotemporal confinement of the treatment in the vicinity of the diseased tissue, which offers many intriguing possibilities. Engineering therapeutics with light responsive moieties have been explored to enhance the bioavailability, and drug efficacy either in vitro or in vivo. The tailor-made character turns the so-called photocaged compounds highly desirable to reduce the side effects of drugs and, therefore, have received wide research attention. Herein, we seek to highlight the potential of photocaged compounds to obtain a clear understanding of the mechanisms behind its use in therapeutic delivery. A deep overview on the progress achieved in the design, fabrication as well as current and possible future applications in therapeutics of photocaged compounds is provided, so that novel formulations for biomedical field can be designed.
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•Engineering therapeutics with photoprotecting groups using straightforward methods of conjugation•On-demand delivery of bioactive molecules by light triggering stimulus•Simple and versatile way to improve therapeutic delivery efficacy
The use of nanoparticles (NPs) in nanomedicine holds great promise for the treatment of diseases for which conventional therapies present serious limitations. Additionally, NPs can drastically ...improve early diagnosis and follow-up of many disorders. However, to harness their full capabilities, they must be precisely designed, produced, and tested in relevant models. Microfluidic systems can simulate dynamic fluid flows, gradients, specific microenvironments, and multiorgan complexes, providing an efficient and cost-effective approach for both NPs synthesis and screening. Microfluidic technologies allow for the synthesis of NPs under controlled conditions, enhancing batch-to-batch reproducibility. Moreover, due to the versatility of microfluidic devices, it is possible to generate and customize endless platforms for rapid and efficient in vitro and in vivo screening of NPs' performance. Indeed, microfluidic devices show great potential as advanced systems for small organism manipulation and immobilization. In this review, first we summarize the major microfluidic platforms that allow for controlled NPs synthesis. Next, we will discuss the most innovative microfluidic platforms that enable mimicking in vitro environments as well as give insights into organism-on-a-chip and their promising application for NPs screening. We conclude this review with a critical assessment of the current challenges and possible future directions of microfluidic systems in NPs synthesis and screening to impact the field of nanomedicine.
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