Chitosan-Halloysite Nano-Composite for Scaffolds for Tissue Engineering

Introduction: regenerative medicine and tissue engineering are emerging disciplines that seek to restore the function of damaged tissues and organs through technological innovations. These areas combine biology, engineering, and medicine to develop solutions that improve patients' quality of life. In this context, scaffolding technologies, stem cell engineering, and bioprinting stand out as key tools for tissue repair and organ regeneration.Development: scaffolds are three-dimensional structures that provide physical support for cell growth and tissue formation. They can be designed with biocompatible materials that mimic the properties of natural tissue, facilitating integration with the body. Stem cell engineering, on the other hand, allows for the extraction and differentiation of cells with regenerative potential, which is crucial for repairing damage to specific tissues. Bioprinting, an innovative technique, uses 3D printers to create complex cellular structures, enabling the manufacture of personalized tissues and artificial organs. These technologies have shown promising results in preclinical and clinical studies, offering new hope in the treatment of degenerative diseases, traumatic injuries, and birth defects.Conclusions: innovations in scaffolding technologies, stem cell engineering, and bioprinting are opening up new possibilities for tissue and organ repair and regeneration. As these technologies continue to evolve, it is critical to address the associated ethical and regulatory challenges to ensure their safe and effective implementation in clinical practice.

Epoxy resins are widely used in various industrial fields due to their low cost, good workability, heat resistance, and good mechanical strength. However, they suffer from brittleness, an issue that must be addressed for further applications. To solve this problem, additional fillers are needed to improve the mechanical and thermal properties of the resins; zirconia is one such filler. However, it has been reported that aggregation may occur in the epoxy composites as the amount of zirconia increases, preventing enhancement of the mechanical strength of the epoxy composites. Herein, to reduce the aggregation, zirconia was well dispersed on halloysite nanotubes (HNTs), which have high thermal and mechanical strength, by a conventional wet impregnation method. The HNTs were impregnated with zirconia at different loadings using zirconyl chloride octahydrate as a precursor. The mechanical and thermal strengths of the epoxy composites with these fillers were investigated. The zirconia-impregnated HNTs (Zr/HNT) were characterized by X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and tunneling electron microscopy (TEM). The hardening conditions of the epoxy composites were analyzed by differential scanning calorimetry (DSC). The thermal strength of the epoxy composites was studied by thermomechanical analysis (TMA) and micro-calorimetry and the mechanical strength of the epoxy composites (flexural strength and tensile strength) was studied by using a universal testing machine (UTM). The mechanical and thermal strengths of the epoxy composites with Zr/HNT were improved compared to those of the epoxy composite with HNT, and also increased as the zirconia loading on HNT increased.

The extracellular matrix (ECM) is a complex network with multiple functions during tissue regeneration. Precisely, the properties of ECM have been thoroughly used in tissue engineering and regenerative medicine research, aiming to restore the function of damaged or dysfunctional tissues. One of the most promising techniques for tissue and organ regeneration is decellularization, in which the ECM is isolated from its native tissues in order to produce a natural scaffold. The ECM ideally retains its inherent structural, biochemical, and biomechanical cues and can be decellularized to produce a functional tissue or organ. While decellularization can be accomplished using chemical and enzymatic, physical, or a combination of these methods, each strategy has its benefits and drawbacks. A biological scaffold from ECM can be produced by a variety of decellularization methods whose caveat consists in efficiently eliminating cells from the treated tissue. Preservation of the ECM matrix ultrastructure is highly desirable because of its unique architecture, contained growth factors, and decreased immunological response. All of these properties provide attachment sites and adequate environment for the cells colonizing this scaffold, reconstituting the decellularized organ. Tissue decellularization is gaining momentum as a technique to obtain potentially implantable decellularized extracellular matrix (dECM) with well-preserved key components. The chapter briefly describes different decellularization methods, evaluates these protocols, and compares the advantages and disadvantages of these methods in terms of their ability to retain desired ECM characteristics for particular tissues and organs.Key wordsExtracellular matrixNaturally derived biomaterialsScaffoldsChemical decellularizationDetergentCell lysisRegenerative medicine

Tissue engineering combines cell and molecular biology with materials and mechanical engineering to replace damaged or diseased organs and tissues. Fibrin is a critical blood component responsible for hemostasis, which has been used extensively as a biopolymer scaffold in tissue engineering. In this review we summarize the latest developments in organ and tissue regeneration using fibrin as the scaffold material. Commercially available fibrinogen and thrombin are combined to form a fibrin hydrogel. The incorporation of bioactive peptides and growth factors via a heparin-binding delivery system improves the functionality of fibrin as a scaffold. New technologies such as inkjet printing and magnetically influenced self-assembly can alter the geometry of the fibrin structure into appropriate and predictable forms. Fibrin can be prepared from autologous plasma, and is available as glue or as engineered microbeads. Fibrin alone or in combination with other materials has been used as a biological scaffold for stem or primary cells to regenerate adipose tissue, bone, cardiac tissue, cartilage, liver, nervous tissue, ocular tissue, skin, tendons, and ligaments. Thus, fibrin is a versatile biopolymer, which shows a great potential in tissue regeneration and wound healing.

Augmentin loaded functionalized halloysite nanotubes: A sustainable emerging nanocarriers for biomedical applications

In this study the compressive strength and durability of soft clay soil stabilized with halloysite nanotubes are investigated. Halloysite nanotubes are novel 1D natural nanomaterials which are widely used in reinforcing polymer, pollution remediation, and as nanoreactors for biocatalyst. The wide use of halloysite nanotubes is due to their high aspect ratio, appropriate mechanical strength, high thermal stability, nature-friendly and cost-effectiveness. However, the use of halloysite nanotubes as a stabilizing agent for improving the durability of soil is not clear. In this research, halloysite nanotubes was used in the amounts of 2%, 5% and 10% by the weight of dried soil. Unconfined compressive strength, wet/dry cycles and freeze/thaw cycles tests were performed to evaluate the strength and durability of stabilized soft clay soil. Experimental results showed that halloysite nanotubes considerably improves the compressive strength and durability of soft clay soil. The optimum amount of halloysite nanotubes for soil stabilizing in terms of compressive strength and durability was 5%. The compressive strength of soft clay increased as much as 129% by applying 5% halloysite nanotubes. Also, the specimen containing 5% halloysite nanotubes showed the least strength loss after wet/dry and freeze/thaw cycles. The soil sample containing 5% halloysite nanotubes lost 20% of its initial compressive strength after 8 cycles of freezing and thawing, while the soil sample without any halloysite content lost 100% of its compressive strength after the same number of freezing and thawing. Based on the obtained results, the use of halloysite nanotubes in order to enhance the strength and durability of soft clay is strongly recommended.

Crash box is one of the equipment to minimize the damage that may occur during an accident in vehicles. Many studies are conducted to improve the performance of crash boxes. Some of these studies were aimed at filling thin‐walled crash boxes. Halloysite nanotubes (HNT) were used as filling material in this study. HNT can be found in nature and is in nanotube structure by nature. For this reason, it is inexpensive compared to other nanotubes like carbon nanotube. Within the scope of the study, epoxy‐based mixtures with 0%, 5%, 10%, and 15% HNT were prepared and filled into aluminum tubes. The powders used were ~20–100 nm in size and in the form of cylindrical tubes. Investigated were the effects of the HNT ratio and the thin‐walled aluminum construction. Nine diverse types of specimens were created. The vacuuming principle was used as the production method. The reason for this is to minimize the air bubbles that may occur during mixing. The effect of aluminum tube and HNT ratio on energy absorption and mechanical strength was investigated. For this, quasi‐static tests were conducted. The absorbed energies of the specimens were determined by integrating the acquired contact force–displacement curves, and the specific absorbed energy was determined by dividing the absorbed energy by the specimen weights. SEM images were taken for internal structure characterization. In addition, FTIR analysis was performed to determine whether the composite was cured. According to the results obtained, the mechanical characteristics and specific absorbed energy of the filled specimens were superior to those of the unfilled ones. Specimen containing 5% HNT showed maximum energy absorption and mechanical strength. Although the HNT additive has a positive effect on the mechanical and energy absorption in general, it has been determined that the HNT additive affects the performances negatively from 10%.

As a unique tubular nanoclay, halloysite nanotubes (HNTs) have recently attracted significant research attention. The HNTs have outer diameters of ∼50 nm, inner lumens of ∼20 nm and are 200–1000 nm long. They are biocompatible nanomaterials and widely available in nature, which makes them good candidates for application in biomedicine. Compared with other types of nanoparticles such as polymer nanoparticles and carbon nanotubes, the drawbacks associated with HNTs include brittleness, difficulty with fabrication, low fracture strength, high density and inadequate biocompatibility. Preparation of polysaccharide-HNT composites offer a means to overcome these shortcomings. Halloysite nanotubes can be incorporated easily into polysaccharides via solution mixing, such as with chitosan (CS), sodium alginate, cellulose, pectin and amylose, for forming composite films, porous scaffolds or hydrogels. The interfacial interactions, such as electrostatic attraction and hydrogen bonding, between HNTs and the polysaccharides are critical for improvement of the properties. Morphology results show that HNTs are dispersed uniformly in the composites. The mechanical strength and Young's modulus of the composites in both the dry and wet states are enhanced by HNTs and the HNTs can also increase the storage modulus, glass-transition temperature and thermal stability of the composites. Cytocompatibility results demonstrate that the polysaccharide-HNT composites have low cytotoxicity even for HNT loading >80%. Therefore, the polysaccharide-HNT composites show great potential for biomedical applications, e.g. as tissue engineering scaffold materials, wound-dressing materials, drug-delivery carriers, and cell-isolation surfaces.

Over the past decades, tissue regeneration with scaffolds has achieved significant progress that would eventually be able to solve the worldwide crisis of tissue and organ regeneration. While the recent advancement in additive manufacturing technique has facilitated the biofabrication of scaffolds mimicking the host tissue, thick tissue regeneration remains challenging to date due to the growing complexity of interconnected, stable, and functional vascular network within the scaffold. Since the biological performance of scaffolds affects the blood vessel regeneration process, perfect selection and manipulation of biological factors (i.e., biopolymers, cells, growth factors, and gene delivery) are required to grow capillary and macro blood vessels. Therefore, in this study, a brief review has been presented regarding the recent progress in vasculature formation using single, dual, or multiple biological factors. Besides, a number of ways have been presented to incorporate these factors into scaffolds. The merits and shortcomings associated with the application of each factor have been highlighted, and future research direction has been suggested.

Chitosan-based hydrogels are being widely used in biomedical applications due to their eco-friendly, biodegradable, and biocompatible properties, and their ability to mimic the extracellular matrix of many tissues. However, the application of chitosan hydrogels has been limited due to their inherent mechanical weakness. Halloysite nanotubes (HNTs) are naturally occurring aluminosilicate clay minerals and are widely used as a bulk filler to improve the performance characteristics of many polymeric materials. HNTs have also been shown to be a viable nanocontainer able to provide the sustained release of antibiotics, chemicals, and growth factors. This study’s objective was to develop a stable drug delivery chitosan/HNT nanocomposite hydrogel that is biocompatible, biodegradable, and provides sustained drug release. In this study, chitosan/HNTs hydrogels containing undoped or gentamicin-doped HNTs were combined in different wt./wt. ratios and cross-linked with tripolyphosphate. The effects of chitosan and HNTs concentration and combination ratios on the hydrogel surface morphology, degradability, and mechanical properties, as well as its drug release capability, were analyzed. The results clearly showed that the addition of HNTs improved chitosan mechanical properties, but only within a narrow range. The nanocomposite hydrogels provided a sustained pattern of drug release and inhibited bacterial growth, and the live/dead assay showed excellent cytocompatibility.

Tissue repair and regeneration are crucial biological processes that restore the structure and function of damaged tissues. While traditionally viewed as a system primarily responsible for defending against pathogens, the immune system plays a pivotal role in mediating tissue repair and regeneration. Immune cells, including macrophages, neutrophils, T cells, and mast cells, coordinate the complex stages of healing, from the initial inflammatory response to tissue remodeling. These immune cells interact with resident tissue cells and secrete cytokines and growth factors that regulate cellular proliferation, angiogenesis, and scar formation. Macrophages, in particular, are versatile, shifting between pro-inflammatory (M1) and anti-inflammatory (M2) states to support different phases of healing. Dysregulation of immune responses can lead to chronic inflammation or excessive fibrosis, impairing proper tissue repair. Recent advancements in understanding the immune mechanisms involved in tissue regeneration have opened new therapeutic avenues for enhancing healing in cases of chronic wounds, heart damage, and other conditions with limited regenerative capacity. This review explores the roles of immune cells and signaling molecules in tissue repair, highlighting their potential as targets for therapies that promote regeneration and reduce fibrosis. Additionally, it discusses the challenges and future directions in the field of regenerative medicine, including personalized immune modulation and biomaterials that enhance immune-mediated healing. Keywords: Tissue regeneration, Immune system, Macrophages, Cytokines, Inflammation

A review of regulated self-organizing approaches for tissue regeneration

Suitable alternatives are made for damaged or diseased organs and tissues in tissue engineering by combining cellular and molecular biology with materials and mechanical engineering. Fibrin is a critical blood component responsible for homeostasis, used extensively as a biopolymer scaffold in tissue engineering. This study summarizes the latest developments in organ and tissue regeneration using fibrin as a scaffold material. The combination of active peptides and growth factors through a heparin-bound delivery system improves fibrin function as a scaffold. Besides, the development of fibrin precursors as recombinant proteins solves multiple or single donor fibrin adhesives. Its composite allows biomolecules to be combined with fibrin and can significantly enhance fibrin efficacy in cartilage tissue engineering applications.

The potential use of growth factors in stem cell-based therapies for the repair and regeneration of tissues and organs offers a paradigm shift in regenerative medicine. Growth factors are critical signalling molecules that play an important role in tissue development and remodelling. Plasma rich in growth factor (PRGF) is a biotechnological strategy for the harvesting of the active substances of platelets, including growth factors, from the patient's blood. Because of their tremendous essential growth factor and bioactive agents, as well as their paracrine mechanisms, PRGF has been used as an efficacious option and adjuvant biological therapy in the repair and replacement of damaged organs. This article provides an overview of PRGF extraction and its properties and critically reviewed its clinical benefit and clinical trials in the treatment and regeneration of human organs. Regenerative medicine is a multi-billion-dollar industry with huge interest to clinicians, academics and industries, being considered as an emerging technology.

The influence of the nerve in regeneration of the amphibian extremity.