Phase‐Transited Lysozyme as a Universal Route to Bioactive Hydroxyapatite Crystalline Film

A key factor for successful design of bioactive complex, organic–inorganic hybrid biomaterials is the facilitation and control of adhesion at interfaces, as many current synthetic biomaterials are inert, lacking interfacial bioactivity. In this regard, the development of a simple, unified way to biofunctionalize diverse organic and inorganic materials toward biomineralization remains a critical challenge. In this report, a universal biomimetic mineralization route that can be applied to virtually any type and morphology of scaffold materials is provided to induce nucleation and growth of hydroxyapatite (HAp) crystals based on phase‐transited lysozyme (PTL) coating. Surface‐anchored abundant functional groups in the PTL enrich the interface with strongly bonded calcium ions, facilitating the formation of HAp crystals in simulated body fluid with the morphology and alignment being similar to that observed in natural HAp in mineralized tissues. By the adhesion of amyloid contained in the PTL, such protein assembly could readily integrate HAp on ceramics, metals, semiconductors, and synthetic polymers irrespective of their size and morphology, with robust bonding stability and corresponding ultralow wear extent under normal bone pressure. This strategy successfully improves the in vivo osteoconductivity of Ti‐based implant, underpinning the expectation for such biomaterial in future biointerface and tissue engineering.     

Biomimetic Mineralized Organic–Inorganic Hybrid Macrofiber with Spider Silk‐Like Supertoughness

Spider silk fibers (SSF) have a hierarchical structure composed of proteins with highly repetitive sequences and biomineralization is sophisticated in hierarchical organic–inorganic constructions. By using inorganic hydroxyapatite (HAP) and organic polyvinyl alcohol (PVA) to simulate the rigid crystalline and flexible amorphous protein blocks of SSF, respectively, biomimetic mineralization is herein attempted for the large‐scale preparation of SSF‐like macrofibers with a hierarchical ordered structure, a superhigh tensile strength of 949 ± 38 MPa, a specific toughness of 296 ± 12 J g^?1, and a stretch ability of 80.6%. The hybrid macrofibers consist of microfibers, and their outstanding performance (e.g., extreme tolerance to temperatures ranging from ?196 to 80 °C and superior ability to inhibit the transverse growth of cracks) is attributed to the hierarchical arrangement as well as the organic–inorganic integrated structure within the oriented mineralized polymer chains. The biomineralization‐inspired technique provides a promising tactic that can be used to synthesize functional organic–inorganic fibers that are structurally complex and, furthermore, industrially manufacture SSF‐like artificial fibers with a supertoughness.     

Variations in Atomic Disorder in Biogenic Carbonate Hydroxyapatite Using the Infrared Spectrum Grinding Curve Method

Biogenic carbonate hydroxyapatite crystals are inherently disordered at the atomic level due mainly to the substitutions of various ions in the crystal structure, and, in the case of the bone family of materials, to the fact that these very small crystals have a very large surface‐to‐bulk ratio. Characterization of the extent of disorder is of much interest, as this relates to the stability and hence solubility of the crystals. Here the infrared spectrometry grinding curve approach developed for calcite, is adapted to carbonate hydroxyapatites. The infrared splitting factor is plotted against the full width at half height of the strong phosphate absorption peak as a function of increased grinding of the sample. By doing so, the contribution of particle size to the shape of the peaks is better separated from the contribution of atomic disorder to peak shape. It is shown that differences in disorder exist between dentine, cementum, and bone crystals which could reflect crystal size and/or atomic defects within the crystal. It is als shown that systematic differences exist between enamel samples from different taxa, which we assume only reflects atomic disorder differences within these large crystals. The method can be used to characterize atomic disorder in natural hydroxyapatites, as well as in the many different types of synthetic hydroxyapatites used for biomedical implants.     

Cover Picture:Transparent Zeolite–Polymer Hybrid Materials with Adaptable Properties (Adv. Funct. Mater. 14/2007)

On p. 2298, Gion Calzaferri and co‐workers of the University of Bern, Switzerland report on a new, simple preparation procedure for highly transparent zeolite‐polymer hybrid materials and polymer covered zeolite L monolayers. The thus‐obtained new transparent host–guest inorganic–organic hybrid materials offer fascinating novel possibilities for the development of optical devices such as lenses, special mirrors, filters, polarizer, grids, optical storage devices, and windows. We report here on a simple preparation procedure for highly transparent zeolite‐polymer hybrid materials and polymer covered zeolite L monolayers. Wrapping up zeolites containing, e.g., dye molecules as guest species with alkoxysilane derivatives results in an efficient dispersion of the nano particles into the organic liquid monomer. The following copolymerisation process leads to a hard, insoluble and transparent material containing zeolites. Optical properties such as colour, luminescence, refractive index or photochromism can be adapted by simply changing the type and amount of the guest in the zeolite crystals, while transparency is maintained.     

Hierarchical Calcite Crystals with Occlusions of a Simple Polyelectrolyte Mimic Complex Biomineral Structures

Biominerals are complex inorganic‐organic structures that often show excellent mechanical properties. Here a bio‐inspired study of a remarkably simple synthetic system is presented in which only one charged polymer additive (poly(sodium 4‐styrenesulfonate)) is able to induce hierarchical structuring of calcite similar to biominerals. The interaction of the negatively charged polymer with the nucleation and growth of the mineral, in particular via selective adsorption to internal and external (001) facets of the calcite lattice, implies structural features from the micrometer down to the nanometer level. The crystals exhibit a distinct rounded morphology and a controlled orientation. Moreover, the polymer molecules are occluded within the crystals with different concentrations in well‐defined regions. This leads to the induction of a mesoscale structure based on 100 nm sized mineral building blocks with granular substructure and rough surface, as well as small modifications of the crystallographic structure. Such a combination of hierarchically organized structural features has previously only been reported for biogenic calcite, which is typically grown in a complex process involving multiple organic additives. It is also shown that the organic occlusions in the calcite‐PSS hybrid crystals strongly affect the mechanical performance, as known for some biominerals.     

Macroscopic Properties of Biomimetic Ceramics Are Governed by the Molecular Recognition at the Bioorganic–Inorganic Interface

Bioinspired materials design aims for high‐performing composite materials based on natural biomineralization processes and biomineral architectures. A key component to the research is the bioorganic–inorganic interface, one of the most crucial parameters for controlling the material properties. In this study, genetically engineered phages expressing an inorganic‐binding peptide for the molecular recognition of a ceramic material is exploited to generate thin film multilayer assemblies, with the phage template as minority component. The bioorganic–inorganic interface in the ceramic (zinc oxide, ZnO) multilayer systems is strengthened by the ZnO‐binding motif HSSHH of a peptide to increase Young's modulus and hardness. Applying a point‐mutated version of the peptide, DSSHH, which modulates the interface forces, shows an increased fracture toughness without deteriorating the Young's modulus and the hardness. Molecular matching of the organic phase and its modulation in order to form a specific interface is shown to be important in controlling material properties like in natural biominerals. With this tool in hand, it is not only possible to imitate the structure of biominerals but also to genetically control the molecular recognition of bioorganic molecules to induce macroscopic effects in synthetic composite materials.     

Multiluminescent Hybrid Organic/Inorganic Nanotubular Structures: One‐Pot Fabrication of Tricolor (Blue–Red–Purple) Luminescent Parallepipedic Organic Superstructure Grafted with Europium Complexes

This article focuses on an innovative one‐pot fabrication of organic/inorganic hybrid parallepipedic tubes with rectangular cavities displaying multicolor luminescence. Firstly, using a novel back‐to‐back coupled 2,6‐di‐pyrazol‐1‐ylpyridine ligand, blue‐emitting several‐micrometer‐long (ca. 50 μm) parallepipedic organic nanotubes with rectangular cavities were fabricated in THF/water via supramolecular (H‐bonding and π–π stacking) and solvent‐assisted self‐assembly. Secondly, in the same pot, the ligand molecules available on the surface of the ligand nanotubes were reacted with Eu(tta)₃ molecules at the solid/liquid interface to form a layer of red‐emitting Eu(III) complex coating on the inner and outer surface of the tubes. The resultant organic/inorganic hybrid parallepipedic nanotubes fabricated using this novel bottom‐up one‐pot technique display tricolor (blue–red–purple) luminescence, i.e., blue and red dual emission from the organic ligand and the Eu(III) complex, respectively, and a purple color due to the mixing of the two colors. This simple technique signifies an innovative and important method in the development of bottom‐up nanotechnology of multiluminescent organic/inorganic hybrid nanotubes.     

Inch‐Size Single Crystal of a Lead‐Free Organic–Inorganic Hybrid Perovskite for High‐Performance Photodetector

Large‐size crystals of organic–inorganic hybrid perovskites (e.g., CH₃NH₃PbX₃, X = Cl, Br, I) have gained wide attention since their spectacular progress on optoelectronic technologies. Although presenting brilliant semiconducting properties, a serious concern of the toxicity in these lead‐based hybrids has become a stumbling block that limits their wide‐scale applications. Exploring lead‐free hybrid perovskite is thus highly urgent for high‐performance optoelectronic devices. Here, a new lead‐free perovskite hybrid (TMHD)BiBr₅ (TMHD = N,N,N,N‐tetramethyl‐1,6‐hexanediammonium) is prepared from facile solution process. Emphatically, inch‐size high‐quality single crystals are successfully grown, the dimensions of which reach up to 32 × 24 × 12 mm³. Furthermore, the planar arrays of photodetectors based on bulk lead‐free (TMHD)BiBr₅ single crystals are first fabricated, which shows sizeable on/off current ratios (≈10³) and rapid response speed (τ_rise = 8.9 ms and τ_decay = 10.2 ms). The prominent device performance of (TMHD)BiBr₅ strongly underscores the lead‐free hybrid perovskite single crystals as promising material candidates for optoelectronic applications.     

Citrate‐Based Tannin‐Bridged Bone Composites for Lumbar Fusion

Conventional bone composites consistently fail to mimic the chemical composition and integrated organic/inorganic structure of natural bone, lacking sufficient mechanics as well as inherent osteoconductivity and osteoinductivity. Through a facile surface coating process, the strong adhesive, tannic acid (TA), is adhered to the surface of the natural bone component, hydroxyapatite (HA), with and without the immobilization of in situ formed silver nanoparticles. Residual functional groups available on the immobilized TA substituents are subsequently covalently linked to the citrate‐based biodegradable polymer, poly(octamethylene citrate) (POC), effectively bridging the organic and inorganic phases. Due to the synergistic effects of the tannin and citrate components, the obtained citrate‐based tannin‐bridged bone composites (CTBCs) exhibit vastly improved compression strengths up to 323.0 ± 21.3 MPa compared to 229.9 ± 15.6 MPa for POC‐HA, and possess tunable degradation profiles, enhanced biomineralization performance, favorable biocompatibility, increased cell adhesion and proliferation, as well as considerable antimicrobial activity. In vivo study of porous CTBCs using a lumbar fusion model further confirms CTBCs' osteoconductivity and osteoinductivity, promoting bone regeneration. CTBCs possess great potential for bone regeneration applications while the immobilized TA additionally preserves surface bioconjugation sites to further tailor the bioactivity of CTBCs.     

Room‐Temperature Tailoring of Vertical ZnO Nanoarchitecture Morphology for Efficient Hybrid Polymer Solar Cells

A ZnO nanoarchitecture, i.e., ZnO nanosheet (NS) framework, is demonstrated to be a promising electron acceptor and direct electron transport matrix for polymer‐inorganic hybrid solar cells. The ZnO NS framework is constructed on nanoneedles/indium tin oxide substrate via a room‐temperature chemical bath deposition (RT CBD). The framework morphology can be simply tailored by varying the concentration of precursor solution in the RT CBD. The ZnO nanoarchitecture with an appropriate free space between the NSs is consequently demonstrated to facilitate poly(3‐hexylthiophene) (P3HT) infiltration, resulting in superior interface properties, i.e., more efficient charge separation and less charge recombination, in the hybrid. Moreover, apart from the characteristics similar to the ZnO nanorod (NR) array, including vertical feature and single crystalline structure, the ZnO NS framework exhibits a slightly larger absorption edge and a faster electron transport rate. A notable efficiency of 0.88% is therefore attained in the ZnO NS‐P3HT hybrid solar cell, which is higher than that of the ZnO NR‐P3HT hybrid solar cell.     

Biomimetic Ultralight,Highly Porous,Shape‐Adjustable,and Biocompatible 3D Graphene Minerals via Incorporation of Self‐Assembled Peptide Nanosheets

Hybrid nanomaterials with tailored functions, consisting of self‐assembled peptides, are intensively applied in nanotechnology, tissue engineering, and biomedical applications due to their unique structures and properties. Herein, a peptide‐mediated biomimetic strategy is adopted to create the multifunctional 3D graphene foam (GF)‐based hybrid minerals. First, 2D peptide nanosheets (PNSs), obtained by self‐assembling a motif‐specific peptide molecule (LLVFGAKMLPHHGA), are expected to exhibit biofunctionality, such as the biomimetic mineralization of hydroxyapatite (HA) minerals. Subsequently, the noncovalent conjugation of PNSs onto GF support is utilized to form 3D GF‐PNSs hybrid scaffolds, which are suitable for the growth of HA minerals. The fabricated biomimetic 3D GF‐PNSs‐HA minerals exhibit adjustable shape, superlow weight (0.017 g cm^?3), high porosity (5.17 m² g^?1), and excellent biocompatibility, proving potential applications in both bone tissue engineering and biomedical engineering. To the best of the authors' knowledge, it is the first time to combine 2D PNSs and GF to fabricate 3D organic–inorganic hybrid scaffold. Further development of these hybrid GF‐PNSs scaffolds can potentially lead to materials used as matrices for drug delivery or bone tissue engineering as proven via successful 3D scaffold formation exhibiting interconnected pore‐size structures suitable for vascularization and medium transport.     

Perovskite‐Based Phototransistors and Hybrid Photodetectors

In the past several years, organic–inorganic hybrid perovskites and all inorganic perovskites have attracted enormous research interest in a variety of optoelectronic applications including solar cells, light‐emitting diodes, semiconductor lasers, and photodetectors for their plenty of appealing electrical and optoelectrical properties. Benefiting from the inherent amplification function of transistors and the pronounced photogating effect, perovskite‐based phototransistors and hybrid photodetectors can provide very high photoresponsivity and gain, rendering them highly promising for some specific applications especially ultrasensitive light detection. A review on the recent progress of phototransistors and hybrid photodetectors using perovskites as light‐sensitive materials is presented. The efforts and development in 3D and 2D perovskite‐based phototransistors, and perovskite/functional material (e.g., graphene, 2D semiconductors, organic semiconductors, and other semiconductors) heterojunction‐based hybrid photodetectors are introduced and discussed systematically. Some processing techniques for optimizing device performance are also addressed. In the final section, a conclusion of the research achievements is presented and possible challenges as well as outlook are provided to guide future activity in this research field.     

Biomaterials that regulate growth factor activity via bioinspired interactions

Growth factor activity is localized within the natural extracellular matrix (ECM) by specific non-covalent interactions with core ECM biomolecules, such as proteins and proteoglycans. Recently, these interactions have inspired us and others to develop synthetic biomaterials that can non-covalently regulate growth factor activity for tissue engineering applications. For example, biomaterials covalently or non-covalently modified with heparin glycosaminoglycans can augment growth factor release strategies. In addition, recent studies demonstrate that biomaterials modified with heparin-binding peptides can sequester cell-secreted heparin proteoglycans and, in turn, sequester growth factors and regulate stem cell behavior. Another set of studies show that modular versions of growth factor molecules can be designed to interact with specific components of natural and synthetic ECMs, including collagen and hydroxyapatite. In addition, layer-by-layer assemblies of GAGs and other natural polyelectrolytes retain growth factors at a cell-material interface via specific non-covalent interactions. This review will detail the various bioinspired strategies being used to non-covalently localize growth factor activity within biomaterials, and will highlight in vivo examples of the efficacy of these materials to promote tissue regeneration.     

Advanced Theragenerative Biomaterials with Therapeutic and Regeneration Multifunctionality

All tissues and organs can be affected by diseases, and treatments for these diseases can cause damage to surrounding healthy tissues and organs. Therefore, treatment is required that involves disease therapy alongside tissue/organ regeneration. The design, construction, and biomedical applications of biomaterial platforms with both disease‐therapeutic and tissue‐regeneration multifunctionalities are in demand, which are herein referred to as theragenerative (abbreviation of therapy and regeneration) biomaterials. Due to the rapid development of theragenerative biomaterials in versatile biomedical applications, this progress report aims to summarize, discuss, and highlight the rational construction of distinctive theragenerative biomaterials with intrinsic therapeutic performance and tissue‐regeneration bioactivity. Based on the intrinsic response to either external physical triggers (e.g., photonic response or magnetic‐field response) or endogenous disease microenvironments (e.g., mild acidity or overexpressed hydrogen peroxide) and tissue‐regeneration bioactivity, these theragenerative biomaterials are extensively explored in various biomedical fields, including bone‐tumor therapy/regeneration, bone antibacterial therapy/regeneration, skin‐tumor therapy/regeneration, skin antibacterial therapy/regeneration, breast‐tumor therapy/adipose‐tissue regeneration, and osteoarticular‐tuberculosis therapy/bone‐tissue regeneration. The challenges faced and future developments of these distinctive theragenerative biomaterials are discussed, as are methods for further promoting their clinical translation.     

Hydroxyapatite/Mesoporous Graphene/Single‐Walled Carbon Nanotubes Freestanding Flexible Hybrid Membranes for Regenerative Medicine

Freestanding flexible membranes based on biocompatible calcium phosphates are of great interest in regenerative medicine. Here, the authors report the first synthesis of well‐aligned biomimetic hexagonal bars of hydroxyapatite (HAp) on flexible, freestanding mesoporous graphene/single‐walled carbon nanotubes (MG/SWCNT) hybrid membranes. The chemical composition and surface morphology of the HAp coating resemble those of biological apatite. Nitrogen doping and oxygen plasma etching of the MG/SWCNT membranes increase the density of nucleation sites and yield more uniform coatings. This novel membrane favors the attachment and proliferation of human fetal osteoblast (hFOB) osteoprogenitor cells. When soaked in simulated body fluid, enhanced in vitro biomineralization occurs on the hybrid membranes. This hybrid membrane holds great promise in biomedical applications such as patches and strips for spine fusion, bone repair, and restoration of tooth enamel.     

Crystal Growth of Calcium Carbonate in Hydrogels as a Model of Biomineralization

In recent years, the prevalence of hydrogel‐like organic matrices in biomineralization has gained attention as a route to synthesizing a diverse range of crystalline structures. Here, examples of hydrogels in biological, as well as synthetic, bio‐inspired systems are discussed. Particular attention is given to understanding the physical versus chemical effects of a broad range of hydrogel matrices and their role in directing polymorph selectivity and morphological control in the calcium carbonate system. Finally, recent data regarding hydrogel‐matrix incorporation into the growing crystals is discussed and a mechanism for the formation of these single‐crystal composite materials is presented.     

Development of a Multifunctional Platform Based on Strong,Intrinsically Photoluminescent and Antimicrobial Silica‐Poly(citrates)‐Based Hybrid Biodegradable Elastomers for Bone Regeneration

Biodegradable biomaterials with intrinsically multifunctional properties such as high strength, photoluminescent ability (bioimaging monitoring), and antimicrobial activity (anti‐infection), as well as high osteoblastic differentiation ability, play a critical role in successful bone tissue regeneration. However, fabricating a biomaterial containing all these functions is still a challenge. Here, urethane cross‐linked intrinsically multifunctional silica‐poly(citrate) (CMSPC)‐based hybrid elastomers are developed by first one‐step polymerization and further chemical crosslinked using isocyanate. CMSPC hybrid elastomers demonstrate a high modulus of 976 ± 15 MPa, which is superior compared with most conventional poly(citrate)‐based elastomers. Hybrid elastomers show strong and stable intrinsic photoluminescent ability (emission 400–600 nm) due to the incorporation of silica phase. All elastomers exhibit high inherent antibacterial properties against Staphylococcus aureus. In addition, CMSPC hybrid elastomers significantly enhance the proliferation and metabolic activity of osteoblasts (MC3T3‐E1). CMSPC hybrid elastomers significantly promote the osteogenic differentiation of MC3T3‐E1 by improving alkaline phosphatase activity and calcium biomineralization deposits, as well as expressions of osteoblastic genes. These hybrid elastomers also show a minimal inflammatory response indicated by subcutaneous transplantation in vivo. These optimized structure and multifunctional properties make this hybrid elastomer highly promising for bone tissue regeneration and antiinfection and bioimaging applications.     

Black‐Phosphorus‐Incorporated Hydrogel as a Conductive and Biodegradable Platform for Enhancement of the Neural Differentiation of Mesenchymal Stem Cells

Conductive hydrogel scaffolds have important applications for electroactive tissue repairs. However, the development of conductive hydrogel scaffolds tends to incorporate nonbiodegradable conductive nanomaterials that will remain in the human body as foreign matters. Herein, a biodegradable conductive hybrid hydrogel is demonstrated based on the integration of black phosphorus (BP) nanosheets into the hydrogel matrix. To address the challenge of applying BP nanosheets in tissue engineering due to its intrinsic instability, a polydopamine (PDA) modification method is developed to improve the stability. Moreover, PDA modification also enhances interfacial bonding between pristine BP nanosheets and the hydrogel matrix. The incorporation of polydopamine‐modified black phosphorous (BP@PDA) nanosheets into the gelatin methacryloyl (GelMA) hydrogels significantly enhances the electrical conductivity of the hydrogels and improves the cell migration of mesenchymal stem cells (MSCs) within the 3D scaffolds. On the basis of the gene expression and protein level assessments, the BP@PDA‐incorporated GelMA scaffold can significantly promote the differentiation of MSCs into neural‐like cells under the synergistic electrical stimulation. This strategy of integrating biodegradable conductive BP nanomaterials within a biocompatible hydrogel provides a new insight into the design of biomaterials for broad applications in tissue engineering of electroactive tissues, such as neural, cardiac, and skeletal muscle tissues.     

Bioinspired Mineral–Organic Bone Adhesives for Stable Fracture Fixation and Accelerated Bone Regeneration

The use of hydrogel‐based bone adhesives has the potential to revolutionize the clinical treatment of bone repairs. However, severe deficiencies remain in current products, including cytotoxicity concerns, inappropriate mechanical strength, and poor fixation performance in wet biological environments. Inspired by the unique roles of glue molecules in the robust mechanical strength and fracture resistance of bone, a design strategy is proposed using novel mineral–organic bone adhesives for strong water‐resistant fixation and guided bone tissue regeneration. The system leveraged tannic acid (TA) as a phenolic glue molecule to spontaneously co‐assemble with silk fibroin (SF) and hydroxyapatite (HA) in order to fabricate the inorganic–organic hybrid hydrogel (named SF@TA@HA). The combination of the strong affinity between SF and TA along with sacrificial coordination bonds between TA and HA significantly improves the toughness and adhesion strength of the hydrogel by increasing the amount of energy dissipation at the nanoscale. This in turn facilitated adequate and stable fixation of bone fracture in wet biological environments. Furthermore, SF@TA@HA promotes the regeneration of bone defects at an early stage in vivo. This work presents a type of bioinspired bone adhesive that is able to provide stable fracture fixation and accelerated bone regeneration during the bone remodeling process.     

Thermodynamic Aspects of Molluscan Shell Ultrastructural Morphogenesis

Over the years, molluscan shells have become an exemplar model system to study the process of mineral formation by living organisms, the process of biomineralization. Typically, the shells consist of a number of mineralized ultrastructural motifs, each exhibiting a specific mineral‐organic composite architecture. These are made of calcium carbonate building blocks having a well‐defined three‐dimensional morphology that is significantly different from the shape of inorganically formed counterparts. Shell ultrastructures are known to form via a biologically controlled extracellular mineralization pathway in which the organism has no direct control over mineral formation. The cellular tissue, responsible for shell biomineralization, forms an organic framework and sets‐up the physical conditions necessary for the deposition of a specific morphology, whereas the growth of the mineral part of the shell proceeds spontaneously via the process of self‐assembly. In this feature article, the ability to employ thermodynamic models from classical materials science to describe the process of self‐assembly and structural evolution of a variety of shell architectures is reviewed. Having the potential to offer an analytical framework to express ultrastructure formation in time and in space, these models not only provide a deeper insight into shell biomineralization, but also suggest tools for novel composite materials design.