ABSTRACT
Numerous small biomolecules exist in the human body and play roles in various biological and pathological processes. Small molecules are believed not to induce intrafibrillar mineralization alone. They are required to work in synergy with noncollagenous proteins (NCPs) and their analogs, e.g. polyelectrolytes, for inducing intrafibrillar mineralization, as the polymer-induced liquid-like precursor (PILP) process has been well-documented. In this study, we demonstrate that small charged molecules alone, such as sodium tripolyphosphate, sodium citrate, and (3-aminopropyl) triethoxysilane, could directly mediate fibrillar mineralization. We propose that small charged molecules might be immobilized in collagen fibrils to form the polyelectrolyte-like collagen complex (PLCC) via hydrogen bonds. The PLCC could attract CaP precursors along with calcium and phosphate ions for inducing mineralization without any polyelectrolyte additives. The small charged molecule-mediated mineralization process was evidenced by Cryo-TEM, AFM, SEM, FTIR, ICP-OES, etc., as the PLCC exhibited both characteristic features of collagen fibrils and polyelectrolyte with increased charges, hydrophilicity, and density. This might hint at one mechanism of pathological biomineralization, especially for understanding the ectopic calcification process.
Subject(s)
Sodium Citrate , Sodium Citrate/chemistry , Sodium Citrate/metabolism , Animals , Humans , Citrates/chemistry , Collagen/chemistry , Collagen/metabolism , Calcinosis/metabolism , Calcinosis/pathology , Propylamines/chemistryABSTRACT
An obstacle in current tumor immunotherapies lies in the challenge of achieving sustained and tumor-targeting T cell immunity, impeded by the limited antigen processing and cross-presentation of tumor antigens. Here, we propose a hydrogel-based multicellular immune factory within the body that autonomously converts tumor cells into an antitumor vaccine. Within the body, the scaffold, formed by a calcium-containing chitosan hydrogel complex (ChitoCa) entraps tumor cells and attracts immune cells to establish a durable and multicellular microenvironment. Within this context, tumor cells are completely eliminated by antigen-presenting cells (APCs) and processed for cross-antigen presentation. The regulatory mechanism relies on the Mincle receptor, a cell-phagocytosis-inducing C-type lectin receptor specifically activated on ChitoCa-recruited APCs, which serves as a recognition synapse, facilitating a tenfold increase in tumor cell engulfment and subsequent elimination. The ChitoCa-induced tumor cell processing further promotes the cross-presentation of tumor antigens to prime protective CD8+ T cell responses. Therefore, the ChitoCa treatment establishes an immune niche within the tumor microenvironment, resulting in effective tumor regression either used alone or in combination with other immunotherapies. This hydrogel-induced immune factory establishes a functional organ-like multicellular colony for tumor-specific immunotherapy, paving the way for innovative strategies in cancer treatment.
Subject(s)
Hydrogels , Immunotherapy , Lectins, C-Type , Immunotherapy/methods , Animals , Hydrogels/chemistry , Lectins, C-Type/metabolism , Humans , Cell Line, Tumor , Neoplasms/therapy , Neoplasms/immunology , Mice, Inbred C57BL , Tumor Microenvironment/immunology , Chitosan/chemistry , Antigen-Presenting Cells/immunology , Cancer Vaccines/immunology , Mice , Membrane Proteins/metabolism , Receptors, Immunologic/metabolism , CD8-Positive T-Lymphocytes/immunologyABSTRACT
Correction for 'Phosphorylation of collagen fibrils enhances intrafibrillar mineralization and dentin remineralization' by Bo Zheng et al., Nanoscale, 2024, https://doi.org/10.1039/d4nr00652f.
ABSTRACT
The regulation of physiochemical behaviors by changing molecular weights is an important cornerstone of polymer physics. However, similar correlations between molecular weights and properties have not been discovered in inorganic ionic compounds. In this work, we prepared a calcium carbonate specimen with a semiflexible chain topology analogous to those of polymers. The molecular weights of the calcium carbonate chains, which ranged from 3400 to 54â¯100 Da, were directly correlated to their physiochemical behaviors, including gel point, zero shear viscosity, and plateau modulus. The calcium carbonate chains showed similar polymeric characteristics, including shear thinning, thixotropy, entropic elasticity, and viscoelasticity. These features agreed with recent theories and formulas in polymer physics textbooks. On the basis of this understanding, the mechanical properties of calcium carbonate-based gels could be altered by changing their molecular weights. This study could represent a fusion of inorganic chemistry and polymer physics with similar molecular weight-dependent behaviors and material properties, establishing an alternative pathway for designing future inorganic materials.
ABSTRACT
The hierarchical assembly of nanoapatite within a type I collagen matrix was achieved through biomimetic mineralization in vitro, cooperatively regulated by non-collagenous proteins and small biomolecules. Here, we demonstrated that IP6 could significantly promote intrafibrillar mineralization in two- and three-dimensional collagen models through binding to collagen fibrils via hydrogen bonds (the interaction energy â¼10.21 kJ mol-1), as confirmed by the FTIR spectra and isothermal experimental results. In addition, we find that IP6 associated with dental collagen fibrils can also enhance the remineralization of calcium-depleted dentin and restore its mechanical properties similar to the natural dentin within 4 days. The promoting effect is mainly due to the chemical modification of IP6, which alters the interfacial physicochemical properties of collagen fibrils, strengthening the interaction of calcium phosphate minerals and mineral ions with collagen fibrils. This strategy of interfacial regulation to accelerate the mineralization of collagen fibrils is essential for dental repair and the development of a clinical product for the remineralization of hard tissue.
Subject(s)
Dentin , Dentin/chemistry , Dentin/metabolism , Humans , Tooth Remineralization , Collagen/chemistry , Collagen/metabolism , Spectroscopy, Fourier Transform Infrared , Calcium Phosphates/chemistry , Hydrogen Bonding , Collagen Type I/chemistry , Collagen Type I/metabolism , AnimalsABSTRACT
The phosphorylated noncollagenous proteins (NCPs) play a vital role in manipulating biomineralization, while the mechanism of phosphorylation of NCPs in intrafibrillar mineralization of collagen fibril has not been completely deciphered. Poly(vinylphosphonic acid) (PVPA) and sodium trimetaphosphate (STMP) as templating analogs of NCPs induce hierarchical mineralization in cooperation with indispensable sequestration analogs such as polyacrylic acid (PAA) via polymer-induced liquid-like precursor (PILP) process. Herein, STMP-Ca and PVPA-Ca complexes are proposed to achieve rapid intrafibrillar mineralization through polyelectrolyte-Ca complexes pre-precursor (PCCP) process. This strategy is further verified effectively for remineralization of demineralized dentin matrix both in vitro and in vivo. Although STMP micromolecule fails to stabilize amorphous calcium phosphate (ACP) precursor, STMP-Ca complexes facilely permeate into intrafibrillar interstices and trigger phase transition of ACP to hydroxyapatite within collagen. In contrast, PVPA-stabilized ACP precursors lack liquid-like characteristic and crystallize outside collagen due to rigid conformation of PVPA macromolecule, while PVPA-Ca complexes infiltrate into partial intrafibrillar intervals under electrostatic attraction and osmotic pressure as evidenced by intuitionistic 3D stochastic optical reconstruction microscopy (3D-STORM). The study not only extends the variety and size range of polyelectrolyte for PCCP process but also sheds light on the role of phosphorylation for NCPs in biomineralization.
Subject(s)
Calcium Phosphates , Collagen Type I , Polyvinyls , Calcium Phosphates/chemistry , Polyvinyls/chemistry , Collagen Type I/chemistry , Collagen Type I/metabolism , Polyphosphates/chemistry , Animals , Acrylic Resins/chemistry , Dentin/chemistry , Dentin/metabolism , Phosphorylation , Humans , Vinyl Compounds , OrganophosphonatesABSTRACT
Bone is the most common site of metastasis, and although low proliferation and immunoediting at the early stage make existing treatment modalities less effective, the microenvironment-inducing behaviour could be a target for early intervention. Here we report on a spatiotemporal coupling interaction between tumour cells and osteoclasts, and named the tumour-associated osteoclast 'tumasteoclast'-a subtype of osteoclasts in bone metastases induced by tumour-migrasome-mediated cytoplasmic transfer. We subsequently propose an in situ decoupling-killing strategy in which tetracycline-modified nanoliposomes encapsulating sodium bicarbonate and sodium hydrogen phosphate are designed to specifically release high concentrations of hydrogen phosphate ions triggered by tumasteoclasts, which depletes calcium ions and forms calcium-phosphorus crystals. This can inhibit the formation of migrasomes for decoupling and disrupt cell membrane for killing, thereby achieving early prevention of bone metastasis. This study provides a research model for exploring tumour cell behaviour in detail and a proof-of-concept for behaviour-targeting strategy.
Subject(s)
Bone Neoplasms , Osteoclasts , Bone Neoplasms/secondary , Bone Neoplasms/metabolism , Bone Neoplasms/drug therapy , Bone Neoplasms/prevention & control , Osteoclasts/drug effects , Osteoclasts/metabolism , Osteoclasts/pathology , Animals , Humans , Mice , Cell Line, Tumor , Tumor Microenvironment/drug effects , Liposomes/chemistry , FemaleABSTRACT
In situ AFM observations show that when PILP droplets contact a surface, their initial properties are either a liquid with a high interfacial tension (350 mJ m-2) or a soft gel-like material with a low modulus (less than 0.2 MPa). These findings suggest that PILP may initially be liquid-like to infiltrate collagen fibrils, enabling the production of interpenetrating composites, and/or become viscoelastic, to provide a means for moulding minerals.
ABSTRACT
Living organisms in nature, such as magnetotactic bacteria and eggs, generate various organic-inorganic hybrid materials, providing unique functionalities. Inspired by such natural hybrid materials, researchers can reasonably integrate biomaterials with living organisms either internally or externally to enhance their inherent capabilities and generate new functionalities. Currently, the approaches to enhancing organismal function through biomaterial intervention have undergone rapid development, progressing from the cellular level to the subcellular or multicellular level. In this review, we will concentrate on three key strategies related to biomaterial-guided bioenhancement, including biointerface engineering, artificial organelles, and 3D multicellular immune niches. For biointerface engineering, excess of amino acid residues on the surfaces of cells or viruses enables the assembly of materials to form versatile artificial shells, facilitating vaccine engineering and biological camouflage. Artificial organelles refer to artificial subcellular reactors made of biomaterials that persist in the cytoplasm, which imparts cells with on-demand regulatory ability. Moreover, macroscale biomaterials with spatiotemporal regulation characters enable the local recruitment and aggregation of cells, denoting multicellular niche to enhance crosstalk between cells and antigens. Collectively, harnessing the programmable chemical and biological attributes of biomaterials for organismal function enhancement shows significant potential in forthcoming biomedical applications.
ABSTRACT
Reactive Oxygen Species (ROS) refers to a highly reactive class of oxidizing species that have the potential to induce cellular apoptosis and necrosis. Cuproptosis, a type of cell death, is primarily associated with the effects of copper ions. However, the specific relationship between ROS, cuproptosis, and osteosarcoma (OS) remains relatively unexplored. Additionally, there is limited research on the use of cuproptosis in conjunction with oxidative stress for treating OS and inhibiting tumor-induced bone destruction. To address these gaps, a novel treatment approach has been developed for OS and neoplastic bone destruction. This approach involves the utilization of glutathione (GSH) and pH-responsive organic-inorganic mesoporous silica nanoparticles@Cu2S@oxidized Dextran (short for MCD). The MCD material demonstrates excellent cytocompatibility, osteogenesis, tumor suppression, and the ability to inhibit osteoclast formation. The specific mechanism of action involves the mitochondria of the MCD material inhibiting key proteins in the tricarboxylic acid (TCA) cycle. Simultaneously, the generation of ROS promotes this inhibition and leads to alterations in cellular energy metabolism. Moreover, the MCD biomaterial exhibits promising mild-temperature photothermal therapy in the second near-infrared (NIR-II) range, effectively mitigating tumor growth and OS-induced bone destruction in vivo.
ABSTRACT
As a result of the non-directionality of ionic bonds, oppositely charged ions always assemble into closely packed clusters or crystals rather than linear structured ionic species. Here, we generated a series of linear calcium carbonate chains, (Ca2+CO32-)n, with an orientated directionality of the ionic interactions. The formation of these ionic chains with long-range ordered ionic interactions was originally induced by the dipole orientation of the ions and subsequently preserved by capping agents. According to the appropriately established folding-capping model, rational control of the capping effect can regulate the length of the (Ca2+CO32-)n chain within 100 nm, corresponding to n ≤ 250. Our discovery overturns the current understanding of ionic bonding in chemistry and opens a way to control the assembly of inorganic ions at molecular scale, pushing forward a fusion of molecular compounds and ionic compounds that share similar topological control.
ABSTRACT
Amphiphilic biomolecules are abundant in mineralization front of biological hard tissues, which play a vital role in osteogenesis and dental hard tissue formation. Amphiphilic biomolecules function as biosurfactants, however, their biosurfactant role in biomineralization process has never been investigated. This study, for the first time, demonstrates that aggregated amorphous calcium phosphate (ACP) nanoparticles can be reversed into dispersed ultrasmall prenucleation clusters (PNCs) via breakdown and dispersion of the ACP nanoparticles by a surfactant. The reduced surface energy of ACP@TPGS and the electrostatic interaction between calcium ions and the pair electrons on oxygen atoms of C-O-C of D-α-tocopheryl polyethylene glycol succinate (TPGS) provide driving force for breakdown and dispersion of ACP nanoparticles into ultrasmall PNCs which promote in vitro and in vivo biomimetic mineralization. The ACP@TPGS possesses excellent biocompatibility without any irritations to oral mucosa and dental pulp. This study not only introduces surfactant into biomimetic mineralization field, but also excites attention to the neglected biosurfactant role during biomineralization process.
Subject(s)
Nanoparticles , Surface-Active Agents , Biomineralization , Biomimetics , Calcium Phosphates/chemistry , Polyethylene Glycols , Nanoparticles/chemistryABSTRACT
Despite significant efforts utilizing advanced technologies, the contentious debate surrounding the intricate mechanism underlying collagen fibril mineralization, particularly with regard to amorphous precursor infiltration and phase transformation, persists. This work proposes an amorphous calcium phosphate (ACP)-mediated pathway for collagen fibril mineralization and utilizing stochastic optical reconstruction microscopy technology, and has experimentally confirmed for the first time that the ACP nanoparticles can infiltrate inside collagen fibrils. Subsequently, the ACP-mediated phase transformation occurs within collagen fibrils to form HAP crystallites, and significantly enhances the mechanical properties of the mineralized collagen fibrils compared to those achieved by the calcium phosphate ion (CPI)-mediated mineralization and resembles the natural counterpart. Furthermore, demineralized dentin can be effectively remineralized through ACP-mediated mineralization, leading to complete restoration of its mechanical properties. This work provides a new paradigm of collagen mineralization via particle-mediated phase transformation, deepens the understanding of the mechanism behind the mineralization of collagen fibrils, and offers a new strategy for hard tissue repair.
Subject(s)
Collagen , Extracellular Matrix , Collagen/metabolism , Extracellular Matrix/metabolism , Calcium PhosphatesABSTRACT
Alloys often combine different metals to generate superior mechanical properties. However, it is challenging to prepare high mechanical strength minerals with similar strategies. Using calcium carbonate (CaC) and calcium phosphate (CaP) as examples, this work synthesizes a group of compounds with the chemical formulas Ca(CO3 )x (PO4 )2(1- x )/3 (0 < x < 1, CaCPs) by cross-linking ionic oligomers. Unlike mixtures, these CaCPs exhibit a single temperature for the phase transition from amorphous to crystallized CaC (calcite) and CaP (hydroxyapatite). By heat-induced synchronous crystallization, dual-phase CaC/CaP with continuous crystallized boundaries are resembled to alloy-like minerals (ALMs). The mechanical properties of the ALMs are adjusted by tailoring their chemical compositions to reach a hardness of 5.6 GPa, which exceed those of control calcite and hydroxyapatite samples by 430% and 260%, respectively. This strategy expands the chemical scope of inorganic materials and holds promise for preparing high-performance minerals.
ABSTRACT
The strategy of using tumor cells to construct whole-cell cancer vaccines has received widespread attention. However, the limited immunogenicity of inactivated tumor cells and the challenge of overcoming immune suppression in solid tumors have hindered the application of whole-cell-based cancer immune therapy. Inspired by the regulatory effects of MnO2 and spatiotemporal control capability of material layers in cell surface engineering, we developed a manganese (Mn)-mineralized tumor cell, B16F10@MnO2, by inactivating B16F10 melanoma cells with KMnO4 to generate manganese-mineralized tumor cells. The cell-based composite was formed by combining amorphous MnO2 with the membrane structure of cells based on the redox reaction between KMnO4 and tumor cells. The MnO2 layer induced a stronger phagocytosis of ovalbumin (OVA)-expressing tumor cells by antigen presenting cells than formaldehyde-fixed cells did, resulting in specific antigen-presentation in vitro and in vivo and subsequent immune responses. Intratumoral therapy with B16F10@MnO2 inhibited B16F10 tumor growth. Moreover, the infiltration of CD8+ T cells within B16F10 solid tumors and the proportion of central memory T cells both increased in B16F10@MnO2 treated tumor-bearing mice, indicating enhanced adaptive immunity. This study provides a convenient and effective method to improve whole-cell-based anti-tumor therapy.
Subject(s)
Cancer Vaccines , Melanoma, Experimental , Mice , Animals , CD8-Positive T-Lymphocytes , Manganese , Manganese Compounds/pharmacology , Melanoma, Experimental/therapy , Oxides/pharmacology , Immunotherapy/methodsABSTRACT
Photosynthetic energy conversion for high-energy chemicals generation is one of the most viable solutions in the quest for sustainable energy towards carbon neutrality. Microalgae are fascinating photosynthetic organisms, which can directly convert solar energy into chemical energy and electrical energy. However, microalgal photosynthetic energy has not yet been applied on a large scale due to the limitation of their own characteristics. Researchers have been inspired to couple microalgae with synthetic materials via biomimetic assembly and the resulting microalgae-material hybrids have become more robust and even perform new functions. In the past decade, great progress has been made in microalgae-material hybrids, such as photosynthetic carbon dioxide fixation, photosynthetic hydrogen production, photoelectrochemical energy conversion and even biochemical energy conversion for biomedical therapy. The microalgae-material hybrid offers opportunities to promote artificially enhanced photosynthesis research and synchronously inspires investigation of biotic-abiotic interface manipulation. This review summarizes current construction methods of microalgae-material hybrids and highlights their implication in energy and health. Moreover, we discuss the current problems and future challenges for microalgae-material hybrids and the outlook for their development and applications. This review will provide inspiration for the rational design of the microalgae-based semi-natural biohybrid and further promote the disciplinary fusion of material science and biological science.
ABSTRACT
Non-collagenous proteins (NCPs) in the extracellular matrix (ECM) of bone and dentin are known to play a critical regulatory role in the induction of collagen fibril mineralization and are embedded in hyaluronic acid (HA), which acts as a water-retaining glycosaminoglycan and provides necessary biochemical and biomechanical cues. Our previous study demonstrated that HA could regulate the mineralization degree and mechanical properties of collagen fibrils, yet its kinetics dynamic mechanism on mineralization is under debate. Here, we further investigated the role of HA on collagen fibril mineralization and the possible mechanism. The HA modification can significantly promote intrafibrillar collagen mineralization by reducing the electronegativity of the collagen surface to enhance calcium ions (Ca2+) binding capacity to create a local higher supersaturation. In addition, the HA also provides additional nucleation sites and shortens the induction time of amorphous calcium phosphate (ACP)-mediated hydroxyapatite (HAP) crystallization, which benefits mineralization. The acceleration effect of HA on intrafibrillar collagen mineralization is also confirmed in collagen hydrogel and in vitro dentin remineralization. These findings offer a physicochemical view of the regulation effect of carbohydrate polymers in the body on biomineralization, the fine prospect for an ideal biomaterial to repair collagen-mineralized tissues.
ABSTRACT
Conductive nano-materials and electrical stimulation (ES) have been recognized as a synergetic therapy for ordinary excitable tissue repair. It is worth noting that hard tissues, such as bone tissue, possess bioelectrical properties as well. However, insufficient attention is paid to the synergetic therapy for bone defect regeneration via conductive biomaterials with ES. Here, a novel nano-conductive hydrogel comprising calcium phosphate-PEDOT:PSS-magnesium titanate-methacrylated alginate (CPM@MA) was synthesized for electro-inspired bone tissue regeneration. The nano-conductive CPM@MA hydrogel has demonstrated excellent electroactivity, biocompatibility, and osteoinductivity. Additionally, it has the potential to enhance cellular functionality by increasing endogenous transforming growth factor-beta1 (TGF-ß1) and activating TGF-ß/Smad2 signaling pathway. The synergetic therapy could facilitate intracellular calcium enrichment, resulting in a 5.8-fold increase in calcium concentration compared to the control group in the CPM@MA ES + group. The nano-conductive CPM@MA hydrogel with ES could significantly promote electro-inspired bone defect regeneration in vivo, uniquely allowing a full repair of rat femoral defect within 4 weeks histologically and mechanically. These results demonstrate that our synergistic strategy effectively promotes bone restoration, thereby offering potential advancements in the field of electro-inspired hard tissue regeneration using novel nano-materials with ES.
Subject(s)
Calcium , Hydrogels , Animals , Rats , Osteogenesis , Bone Regeneration , Bone and BonesABSTRACT
Material-based tactics have attracted extensive attention in driving the functional evolution of organisms. In aiming to design steerable bioartificial organisms to scavenge pathogenic waterborne viruses, we engineer Paramecium caudatum (Para), single-celled microorganisms, with a semiartificial and specific virus-scavenging organelle (VSO). Fe3O4 magnetic nanoparticles modified with a virus-capture antibody (MNPs@Ab) are integrated into the vacuoles of Para during feeding to produce VSOs, which persist inside Para without impairing their swimming ability. Compared with natural Para, which has no capture specificity and shows inefficient inactivation, the VSO-engineered Para (E-Para) specifically gathers waterborne viruses and confines them inside the VSOs, where the captured viruses are completely deactivated because the peroxidase-like nano-Fe3O4 produces virus-killing hydroxyl radicals (â¢OH) within acidic environment of VSO. After treatment, magnetized E-Para is readily recycled and reused, avoiding further contamination. Materials-based artificial organelles convert natural Para into a living virus scavenger, facilitating waterborne virus clearance without extra energy consumption.
Subject(s)
Viruses , Hydroxyl Radical , Peroxidase , Peroxidases , Antibodies, ViralABSTRACT
Although organic-inorganic hybrid materials have played indispensable roles as mechanical1-4, optical5,6, electronic7,8 and biomedical materials9-11, isolated organic-inorganic hybrid molecules (at present limited to covalent compounds12,13) are seldom used to prepare hybrid materials, owing to the distinct behaviours of organic covalent bonds14 and inorganic ionic bonds15 in molecular construction. Here we integrate typical covalent and ionic bonds within one molecule to create an organic-inorganic hybrid molecule, which can be used for bottom-up syntheses of hybrid materials. A combination of the organic covalent thioctic acid (TA) and the inorganic ionic calcium carbonate oligomer (CCO) through an acid-base reaction provides a TA-CCO hybrid molecule with the representative molecular formula TA2Ca(CaCO3)2. Its dual reactivity involving copolymerization of the organic TA segment and inorganic CCO segment generates the respective covalent and ionic networks. The two networks are interconnected through TA-CCO complexes to form a covalent-ionic bicontinuous structure within the resulting hybrid material, poly(TA-CCO), which unifies paradoxical mechanical properties. The reversible binding of Ca2+-CO32- bonds in the ionic network and S-S bonds in the covalent network ensures material reprocessability with plastic-like mouldability while preserving thermal stability. The coexistence of ceramic-like, rubber-like and plastic-like behaviours within poly(TA-CCO) goes beyond current classifications of materials to generate an 'elastic ceramic plastic'. The bottom-up creation of organic-inorganic hybrid molecules provides a feasible pathway for the molecular engineering of hybrid materials, thereby supplementing the classical methodology used for the manufacture of organic-inorganic hybrid materials.