Ultrasensitive Dual Fluorophore-Conjugated Carbon Dots for Intracellular pH Sensing in 3D Tumor Models.

The dysregulation of pH has been linked to the onset of chronic conditions, such as cancer and neurological diseases. Consequently, the development of a highly sensitive tool for intracellular pH sensing is imperative to investigate the interplay between pH and the biochemical changes accompanying disease pathogenesis. Here, we present the development of a ratiometric fluorescent nanoprobe, , designed for precisely measuring pH levels.

Engineering antibacterial bioceramics: Design principles and mechanisms of action.

The urgency to address skeletal abnormalities and diseases through innovative approaches has led to a significant interdisciplinary convergence of engineering, 3D printing, and design in developing individualised bioceramic bioscaffolds. This review explores into the recent advancements and future trajectory of non-antibiotic antibacterial bioceramics in bone tissue engineering, an importance given the escalating challenges of orthopaedic infections, antibiotic resistance, and emergent pathogens. Initially, the review provides an in-depth exploration of the complex interactions among bacteria, immune cells, and bioceramics in clinical contexts, highlighting the multifaceted nature of infection dynamics, including protein adsorption, immunological responses, bacterial adherence, and endotoxin release.

Unraveling the influence of channel size and shape in 3D printed ceramic scaffolds on osteogenesis.

Bone has the capacity to regenerate itself for relatively small defects; however, this regenerative capacity is diminished in critical-size bone defects. The development of synthetic materials has risen as a distinct strategy to address this challenge. Effective synthetic materials to have emerged in recent years are bioceramic implants, which are biocompatible and highly bioactive.

Osteopontin Rejuvenates Senescent Adipose-Derived Stem Cells and Restores their Bone Tissue Regenerative Function.

The regenerative function of stem cells is compromised when the proportion of senescent stem cells increases with ageing advance. Therefore, combating stem cell senescence is of great importance for stem cell-based tissue engineering in the elderly, but remains largely unexplored. Osteopontin (OPN), a glycosylated phosphoprotein, is one of the key extracellular matrix molecules in bone tissue.

3D spheroid-microvasculature-on-a-chip for tumor-endothelium mechanobiology interplay.

During the final stage of cancer metastasis, tumor cells embed themselves in distant capillary beds, from where they extravasate and establish secondary tumors. Recent findings underscore the pivotal roles of blood/lymphatic flow and shear stress in this intricate tumor extravasation process. Despite the increasing evidence, there is a dearth of systematic and biomechanical methodologies that accurately mimic intricate 3D microtissue interactions within a controlled hydrodynamic microenvironment.

Theta-Gel-Reinforced Hydrogel Composites for Potential Tensile Load-Bearing Soft Tissue Repair Applications.

Engineering synthetic hydrogels for the repair and augmentation of load-bearing soft tissues with simultaneously high-water content and mechanical strength is a long-standing challenge. Prior formulations to enhance the strength have involved using chemical crosslinkers where residues remain a risk for implantation or complex processes such as freeze-casting and self-assembly, requiring specialised equipment and technical expertise to manufacture reliably. In this study, we report for the first time that the tensile strength of high-water content (>60 wt.

Programming of Multicellular Patterning with Mechano-Chemically Microstructured Cell Niches.

Multicellular patterning of stem-cell-derived tissue models is commonly achieved via self-organizing activities triggered by exogenous morphogenetic stimuli. However, such tissue models are prone to stochastic behavior, limiting the reproducibility of cellular composition and forming non-physiological architectures. To enhance multicellular patterning in stem cell-derived tissues, a method for creating complex tissue microenvironments endowed with programmable multimodal mechano-chemical cues, including conjugated peptides, proteins, morphogens, and Young's moduli defined over a range of stiffnesses is developed.

Discovering an unknown territory using atom probe tomography: Elemental exchange at the bioceramic scaffold/bone tissue interface.

Here we report the first atom probe study to reveal the atomic-scale composition of in vivo bone formed in a bioceramic scaffold (strontium-hardystonite-gahnite) after 12-month implantation in a large bone defect in sheep tibia. The composition of the newly formed bone tissue differs to that of mature cortical bone tissue, and elements from the degrading bioceramic implant, particularly aluminium (Al), are present in both the newly formed bone and in the original mature cortical bone tissue at the perimeter of the bioceramic implant. Atom probe tomography confirmed that the trace elements are released from the bioceramic and are actively transported into the newly formed bone.

Protocol for Cell Colonization and Comprehensive Monitoring of Osteogenic Differentiation in 3D Scaffolds Using Biochemical Assays and Multiphoton Imaging.

The goal of bone tissue engineering is to build artificial bone tissue with properties that closely resemble human bone and thereby support the optimal integration of the constructs (biografts) into the body. The development of tissues in 3D scaffolds includes several complex steps that need to be optimized and monitored. In particular, cell-material interaction during seeding, cell proliferation and cell differentiation within the scaffold pores play a key role.

Nicotinamide Mononucleotide Alleviates Osteoblast Senescence Induction and Promotes Bone Healing in Osteoporotic Mice.

Combating the accumulated senescent cells and the healing of osteoporotic bone fractures in the older remains a significant challenge. Nicotinamide mononucleotide (NMN), a precursor of NAD+, is an excellent candidate for mitigating aging-related disorders. However, it is unknown if NMN can alleviate senescent cell induction and enhance osteoporotic bone fracture healing.

Rationally-designed self-shaped ceramics through heterogeneous green body compositions.

Forming ceramics into rationally-designed and complex shapes without compromising their mechanical properties is a major challenge. Here, we demonstrate self-shaping of ceramics through sequential stereolithographic printing of ceramic resins into components with a heterogeneous concentration of ceramic particles, resulting in well-defined anisotropic shrinkage and, consequently, shape changes during sintering. The method is versatile and scalable and results in well-controlled shape changes in ceramics through bending, folding, twisting, and combinations of these mechanisms.

Promise and Perspective of Nanomaterials in Antisenescence Tissue Engineering Applications.

The tissue engineering approach for repair and regeneration has achieved significant progress over the past decades. However, challenges remain in developing strategies to solve the declined or impaired innate cell and tissue regeneration capacity that occurs with aging. Cellular senescence is a key mechanism underlying organismal aging and is responsible for the declined tissue regeneration capacity in the aging population.

Personalized 3D printed bone scaffolds: A review.

3D printed bone scaffolds have the potential to replace autografts and allografts because of advantages such as unlimited supply and the ability to tailor the scaffolds' biochemical, biological and biophysical properties. Significant progress has been made over the past decade in additive manufacturing techniques to 3D print bone grafts, but challenges remain in the lack of manufacturing techniques that can recapitulate both mechanical and biological functions of native bones. The purpose of this review is to outline the recent progress and challenges of engineering an ideal synthetic bone scaffold and to provide suggestions for overcoming these challenges through bioinspiration, high-resolution 3D printing, and advanced modeling techniques.

Low-Temperature Synthesis of Hollow β-Tricalcium Phosphate Particles for Bone Tissue Engineering Applications.

β-Tricalcium phosphate (β-TCP) has been extensively used in bone tissue engineering in the form of scaffolds, granules, or as reinforcing phase in organic matrices. Solid-state reaction route at high temperatures (>1000 °C) is the most widely used method for the preparation of β-TCP. The high-temperature synthesis, however, results in the formation of hard agglomerates and fused particles which necessitates postprocessing steps such as milling and sieving operations.

Stereolithographic Visible-Light Printing of Poly(l-glutamic acid) Hydrogel Scaffolds.

Bioprinting is a promising fabrication technique aimed at developing biologically functional, tissue-like constructs for various biomedical applications. Among the different bioprinting approaches, vat polymerization-based techniques offer the highest feature resolution compared to more commonly used extrusion-based methods and therefore have greater potential to be utilized for printing complex hierarchical tissue architectures. Although significant efforts have been directed toward harnessing digital light processing techniques for high-resolution bioprinting, the use of stereolithography (SLA) setups for producing distinct hydrogel filaments smaller than 20 μm has received less attention.

Design and evaluation of 3D-printed Sr-HT-Gahnite bioceramic for FDA regulatory submission: A Good Laboratory Practice sheep study.

There is an unmet clinical need for a spinal fusion implant material that recapitulates the biological and mechanical performance of natural bone. We have developed a bioceramic, Sr-HT-Gahnite, which has been identified as a potential fusion device material. This material has the capacity to transform the future of the global interbody devices market, with follow on social, economic, and environmental benefits, rooted in its remarkable combination of mechanical properties and bioactivity.

Development of a bioactive and radiopaque bismuth doped baghdadite ceramic for bone tissue engineering.

Baghdadite (CaZrSiO, BAG), is a Zr-doped calcium silicate that has outstanding bioactivity both in vitro and in vivo. Bioceramic scaffolds should be sufficiently radiopaque to be distinguishable in vivo from surrounding bone structures. To enhance the radiopacity of BAG, this study investigated the effect of incorporating bismuth ions into its crystalline structure (BiCaZrSiO, x = 0, 0.

A machine learning-based multiscale model to predict bone formation in scaffolds.

Computational modeling methods combined with non-invasive imaging technologies have exhibited great potential and unique opportunities to model new bone formation in scaffold tissue engineering, offering an effective alternate and viable complement to laborious and time-consuming in vivo studies. However, existing numerical approaches are still highly demanding computationally in such multiscale problems. To tackle this challenge, we propose a machine learning (ML)-based approach to predict bone ingrowth outcomes in bulk tissue scaffolds.

Influence of carbon dot synthetic parameters on photophysical and biological properties.

Recently, carbon dots (CDs) have been widely investigated for biological applications in imaging. One-step hydrothermal synthesis is considered to be one of the most promising methods for the synthesis of CDs, due to its simple and rapid manipulation, flexible selection of ingredients, environmentally friendly conditions, and low-cost. A number of synthetic and post-synthetic parameters, including solvent, heating time, dopant quantity, and particle size distribution, play a crucial role in controlling the size and surface structure of CDs, which ultimately have influence on their photophysical and biological behavior.

Tuneable manganese oxide nanoparticle based theranostic agents for potential diagnosis and drug delivery.

Among various magnetic nanoparticles, manganese oxide nanoparticles are considered as established magnetic resonance imaging (MRI) contrast agents for preclinical research. The implications of their degradation properties and use as therapeutic carriers in drug delivery systems have not been explored. In addition, how the chemical composition and size of manganese oxide nanoparticles, as well as the surrounding environment, influence their degradation and MRI contrast properties ( ) have not been studied in great detail.

Baghdadite coating formed by hybrid water-stabilized plasma spray for bioceramic applications: Mechanical and biological evaluations.

This work studies the mechanical and biological properties of Baghdadite (BAG, CaZrSiO) coating manufactured on Ti6Al4V substrates by hybrid water-stabilized plasma spray (WSP-H). Hydroxyapatite (HAp, Ca(PO)(OH)) coating was produced by gas-stabilized atmospheric plasma spray and used as a reference material. Upon spraying, the BAG coating exhibited lower crystallinity than the HAp coating.

High-Strength Fiber-Reinforced Composite Hydrogel Scaffolds as Biosynthetic Tendon Graft Material.

The development of suitable synthetic scaffolds for use as human tendon grafts to repair tendon ruptures remains a significant engineering challenge. Previous synthetic tendon grafts have demonstrated suboptimal tissue ingrowth and synovitis due to wear particles from fiber-to-fiber abrasion. In this study, we present a novel fiber-reinforced hydrogel (FRH) that mimics the hierarchical structure of the native human tendon for synthetic tendon graft material.

Combination Therapy Using Kartogenin-Based Chondrogenesis and Complex Polymer Scaffold for Cartilage Defect Regeneration.

Articular cartilage has a highly organized structure, responsible for supporting tremendous mechanical loads. How to repair defected articular cartilage has become a great challenge as the avascular nature of cartilage limits its regenerative ability. Aiming to facilitate chondrogenic differentiation and cartilage regeneration, we recently explored a novel combination therapy using soluble poly-l-lysine/Kartogenin (L-K) nanoparticles and a poly(lactic--glycolic acid) PLGA/methacrylated hyaluronic acid (PLHA) complex scaffold.