In Situ Porous Structures: A Unique Polymer Erosion Mechanism in Biodegradable Dipeptide-based Polyphosphazene and Polyester Blends Producing Matrices for Regenerative Engineering

Synthetic biodegradable polymers serve as temporary substrates that accommodate cell infiltration and tissue in-growth in regenerative medicine. To allow tissue in-growth and nutrient transport, traditional three-dimensional (3D) scaffolds must be prefabricated with an interconnected porous structure. Here we demonstrated for the first time a unique polymer erosion process through which polymer matrices evolve from a solid coherent film to an assemblage of microspheres with an interconnected 3D porous structure. This polymer system was developed on the highly versatile platform of polyphosphazene-polyester blends. Co-substituting a polyphosphazene backbone with both hydrophilic glycylglycine dipeptide and hydrophobic 4-phenylphenoxy group generated a polymer with strong hydrogen bonding capacity. Rapid hydrolysis of the polyester component permitted the formation of 3D void space filled with self-assembled polyphosphazene spheres. Characterization of such self-assembled porous structures revealed macropores (10-100 μm) between spheres as well as micro- and nanopores on the sphere surface. A similar degradation pattern was confirmed in vivo using a rat subcutaneous implantation model. 12 weeks of implantation resulted in an interconnected porous structure with 82-87% porosity. Cell infiltration and collagen tissue in-growth between microspheres observed by histology confirmed the formation of an in situ 3D interconnected porous structure. It was determined that the in situ porous structure resulted from unique hydrogen bonding in the blend promoting a three-stage degradation mechanism. The robust tissue in-growth of this dynamic pore forming scaffold attests to the utility of this system as a new strategy in regenerative medicine for developing solid matrices that balance degradation with tissue formation.     

Biomimetic Structures: Biological Implications of Dipeptide‐Substituted Polyphosphazene–Polyester Blend Nanofiber Matrices for Load‐Bearing Bone Regeneration

Successful bone regeneration benefits from three‐dimensional (3D) bioresorbable scaffolds that mimic the hierarchical architecture and mechanical characteristics of native tissue extracellular matrix (ECM). A scaffold platform that integrates unique material chemistry with nanotopography while mimicking the 3D hierarchical bone architecture and bone mechanics is reported. A biocompatible dipeptide polyphosphazene‐polyester blend is electrospun to produce fibers in the diameter range of 50–500 nm to emulate dimensions of collagen fibrils present in the natural bone ECM. Various electrospinning and process parameters are optimized to produce blend nanofibers with good uniformity, appropriate mechanical strength, and suitable porosity. Biomimetic 3D scaffolds are created by orienting blend nanofiber matrices in a concentric manner with an open central cavity to replicate bone marrow cavity, as well as the lamellar structure of bone. This biomimicry results in scaffold stress–strain curve similar to that of native bone with a compressive modulus in the mid‐range of values for human trabecular bone. Blend nanofiber matrices support adhesion and proliferation of osteoblasts and show an elevated phenotype expression compared to polyester nanofibers. Furthermore, the 3D structure encourages osteoblast infiltration and ECM secretion, bridging the gaps of scaffold concentric walls during in vitro culture. The results also highlight the importance of in situ ECM secretion by cells in maintaining scaffold mechanical properties following scaffold degradation with time. This study for the first time demonstrates the feasibility of developing a mechanically competent nanofiber matrix via a biomimetic strategy and the advantages of polyphosphazene blends in promoting osteoblast phenotype progression for bone regeneration.     

The Implications of Polymer Selection in Regenerative Medicine: A Comparison of Amorphous and Semi‐Crystalline Polymer for Tissue Regeneration

Biodegradable polymeric scaffolds are being investigated as scaffolding materials for use in regenerative medicine. While the in vivo evaluation of various three‐dimensional (3D), porous, biodegradable polymeric scaffolds has been reported, most studies are ≤3 months in duration, which is typically prior to bulk polymer degradation, a critical event that may initiate an inflammatory response and inhibit tissue formation. Here, a 6 month in vitro degradation and corresponding in vivo studies that characterized scaffold changes during complete degradation of an amorphous, 3D poly(lactide‐co‐glycolide)(3D‐PLAGA) scaffold and near‐complete degradation of a semi‐crystalline3D‐PLAGA scaffold are reported. Using sintered microsphere matrix technology, constructs were fabricated in a tubular shape, with the longitudinal axis void and a median pore size that mimicked the architecture of native bone. Long‐term quantitative measurements of molecular weight, mechanical properties, and porosity provided a basis for theorization of the scaffold degradation process. Following implantation in a critical size ulnar defect model, histological analysis and quantitative microCT indicated early solubilization of the semi‐crystalline polymer created an acidic microenvironment that inhibited mineralized tissue formation. Thus, the use of amorphous over semi‐crystalline PLAGA materials is advocated for applications in regenerative medicine.     

Densely Interconnected Porous BN Frameworks for Multifunctional and Isotropically Thermoconductive Polymer Composites

Ideal materials for modern electronics packaging should be highly thermoconductive. This may be achieved through designing multifunctional polymer composites. Such composites may generally be achieved via effective embedment of functional inorganic fillers into desirable polymeric bodies. Herein, two types of high‐performance 3D h‐BN porous frameworks (3D‐BN), namely, h‐BN nanorod‐assembled networks and nanosheet‐interconnected frameworks, are successfully created via an in situ carbothermal reduction chemical vapor deposition substitution reaction using carbon‐based nanorod‐interconnected networks as templates. These 3D‐BN porous materials with densely interlinked frameworks, excellent mechanical robustness and integrity, highly isotropous and multiple heat transfer paths, enable reliable fabrications of diverse 3D‐BN/polymer porous composites. The composites exhibit combinatorial multifunctional properties, such as excellent mechanical strength, light weight, ultralow coefficient of thermal expansion, highly isotropic thermal conductivities (≈26–51 multiples of pristine polymers), relatively low dielectric constants and super‐low dielectric losses, and high resistance to softening at elevated temperatures. In addition, the regarded 3D‐BN frameworks are easily recycled from their polymer composites, and may be reliably reutilized for multifunctional reuse. Thus, these materials should be valuable for new‐era advanced electronic packaging and related applications.     

Fabrication of Reversibly Crosslinkable, 3‐Dimensionally Conformal Polymeric Microstructures

Multifaceted porous materials were prepared through careful design of star polymer functionality and properties. Functionalized core crosslinked star (CCS) polymers with a low glass transition temperature (T_g) based on poly(methyl acrylate) were prepared having a multitude of hydroxyl groups at the chain ends. Modification of these chain ends with 9‐anthracene carbonyl chloride introduces the ability to reversibly photocrosslink these systems after the star polymers were self‐assembled by the breath figure technique to create porous, micro‐structured films. The properties of the low T_g CCS polymer allow for the formation of porous films on non‐planar substrates without cracking and photo‐crosslinking allows the creation of stabilized honeycomb films while also permitting a secondary level of patterning on the film, using photo‐lithographic techniques. These multifaceted porous polymer films represent a new generation of well‐defined, 3D microstructures.     

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.     

White‐Emitting Conjugated Polymer/Inorganic Hybrid Spheres: Phenylethynyl and 2,6‐Bis(pyrazolyl)pyridine Copolymer Coordinated to Eu(tta)3

The synthesis of two cyan color (blue and green emission) displaying high molecular weight 2,6‐bis(pyrazolyl)pyridine‐co‐octylated phenylethynyl conjugated polymers (CPs) is presented. The conjugated polymers are solution‐processed to prepare spin coated thin films and self‐assembled nano/microscale spheres, exhibiting cyan color under UV. Additionally, the metal coordinating ability of the 2,6‐bis(pyrazolyl)pyridine available on the surface of the CP films and spheres is exploited to prepare red emitting Eu(III) metal ion containing conjugated polymer (MCCP) layer. The fabricated hybrid (CP/MCCP) films and spheres exhibit bright white‐light under UV exposure. The Commission Internationale de l'Eclairage (CIE) coordinates are found to be (x = 0.33, y = 0.37) for hybrid films and (x = 0.30, y = 0.35) for hybrid spheres. These values are almost close to the designated CIE coordinates for ideal white‐light color (x = 0.33, y = 0.33). This easy and efficient fabrication technique to generate white‐color displaying films and nano/microspheres signify an important method in bottom‐up nanotechnology of conjugated polymer based hybrid solid state assemblies.     

Highly Porous Crosslinkable PLA‐PNB Block Copolymer Scaffolds

Poly(lactic acid) (PLA)‐block‐poly(norbornene) (PNB) copolymers which bear photocrosslinkable cinnamate side‐chains are synthesized by combining the ring‐opening metathesis polymerization (ROMP) of norbornenes with the ring‐opening polymerization (ROP) of lactides. Highly porous 3D scaffolds with tunable pore sizes ranging from 20 to 300 µm are fabricated through liquid–solid phase separation. Scaffolds with an average pore size around 250 µm, which are under investigation as bone grafting materials, are reproducibly obtained from freeze‐drying 5% w/v benzene solutions of PLA‐b‐PNB copolymers at −10 °C. As a demonstration of the impact of photocrosslinking of cinnamate side‐chains, scaffolds are exposed to UV radiation for 8 h, resulting in a 33% increase in the compressive modulus of the polymeric scaffold. The foams and the methodology described herein represent a new strategy toward polymeric scaffolds with potential for use in regenerative medicine applications.     

Functional and Well‐Defined β‐Sheet‐Assembled Porous Spherical Shells by Surface‐Guided Peptide Formation

Polypeptides have attracted widespread attention as building blocks for complex materials due to their ability to form higher‐ordered structures such as β‐sheets. However, the ability to precisely control the formation of well‐defined β‐sheet‐assembled materials remains challenging as β‐sheet formation tends to lead to ill‐defined and unprocessable aggregates. This work reports a simple, rapid, and robust strategy to form well‐defined peptide β‐sheet‐assembled shells (i.e., hollow spheres) by employing surface‐initiated N‐carboxyanhydride ring‐opening polymerization under a highly efficient surface‐driven approach. The concept is demonstrated by the preparation of enzyme‐degradable rigid shell architectures composed of H‐bonded poly(L‐valine) (PVal) grafts with porous and sponge‐like surface morphology. The porous PVal‐shells exhibit a remarkable and unprecedented ability to non‐covalently entrap metal nanoparticles, proteins, drug molecules, and biorelevant polymers, which could potentially lead to a diverse range of biodegradable and functional platforms for applications ranging from therapeutic delivery to organic catalysis.     

Inside Front Cover: Fine Control of the Wettability Transition Temperature of Colloidal‐Crystal Films: From Superhydrophilic to Superhydrophobic (Adv. Funct. Mater. 2/2007)

A facile strategy for finely controlling the wettability transition temperature of colloidal‐crystal films from superhydrophilic to superhydrophobic is demonstrated by Song and co‐workers on p. 219. The films are assembled from poly(styrene‐n‐butyl acrylate–acrylic acid) latex spheres. The wettability transition temperature of the films is tuned by adjusting the n‐butyl acrylate/styrene balance. This approach offers flexibile fabrication of colloidal crystals with tunable wettability, and can be further extended to general materials. A facile strategy for finely controlling the wettability transition temperature of colloidal‐crystal films from superhydrophilic (water contact angle, CA, 0°) to superhydrophobic (water CA, 150.5°) is demonstrated. The colloidal‐crystal films are assembled from poly(styrene‐n‐butyl acrylate–acrylic acid) amphiphilic latex spheres. The wettability transition temperature of the films can be well tuned by adjusting the n‐butyl acrylate/styrene balance of the latex spheres. Superhydrophobic films are achieved when assembled at 90, 80, 70, 60, 40, or even 20 °C. This approach offers the flexibility of fabricating colloidal crystals with desired and tunable wettability, and can be further extended to general materials, opening up new perspectives in controlling the wettability behavior by chemical composition.     

MOF Nano‐Vesicles and Toroids: Self‐Assembled Porous Soft‐Hybrids for Light Harvesting

Metal‐organic vesicular and toroid nanostructures of Zn(OPE)·2H₂O are achieved by coordination‐directed self‐assembly of oligo‐phenyleneethynylenedicarboxylic acid (OPEA) as a linker with Zn(OAc)₂ by controlling the reaction parameters. Self‐assembled nanostructures are characterized by powder X‐ray diffraction, field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), and adsorption study. The amphiphilic nature of the coordination‐polymer with long alkyl chains renders different soft vesicular and toroidal nanostructures. The permanent porosity of the framework is established by gas adsorption study. Highly luminescent 3D porous framework is exploited for Froster's resonance energy transfer (FRET) by encapsulation of a suitable cationic dye ( DSMP ) which shows efficient funneling of excitation energy. These results demonstrate the dynamic and soft nature of the MOF, resulting in unprecedented vesicular and toroidal nanostructures with efficient light harvesting applications.     

Inverted‐Colloidal‐Crystal Hydrogel Matrices as Three‐Dimensional Cell Scaffolds

Successful engineering of functional tissues requires the development of three‐dimensional (3D) scaffolds that can provide an optimum microenvironment for tissue growth and regeneration. A new class of 3D scaffolds with a high degree of organization and unique topography is fabricated from polyacrylamide hydrogel. The hydrogel matrix is molded by inverted colloidal crystals made from 104 μm poly(methyl methacrylate) spheres. The topography of the scaffold can be described as hexagonally packed 97 μm spherical cavities interconnected by a network of channels. The scale of the long‐range ordering of the cavities exceeds several millimeters. In contrast to analogous material in the bulk, hydrogel shaped as an inverted opal exhibits much higher swelling ratios; its swelling kinetics is an order of magnitude faster as well. The engineered scaffold possesses desirable mechanical and optical properties that can facilitate tissue regeneration while allowing for continuous high‐resolution optical monitoring of cell proliferation and cell–cell interaction within the scaffold. The scaffold biocompatibility as well as cellular growth and infiltration within the scaffold were observed for two distinct human cell lines which were seeded on the scaffold and were tracked microscopically up to a depth of 250 μm within the scaffold for a duration of up to five weeks. Ease of production, a unique 3D structure, biocompatibility, and optical transparency make this new type of hydrogel scaffold suitable for most challenging tasks in tissue engineering.     

3D Porous N‐Doped Graphene Frameworks Made of Interconnected Nanocages for Ultrahigh‐Rate and Long‐Life Li–O2 Batteries

The inferior rate capability and poor cycle stability of the present Li–O₂ batteries are still critical obstacles for practice applications. Configuring novel and integrated air electrode materials with unique structure and tunable chemical compositions is one of the efficient strategies to solve these bottleneck problems. Herein, a novel strategy for synthesis of 3D porous N‐doped graphene aerogels (NPGAs) with frameworks constructed by interconnected nanocages with the aid of polystyrene sphere@polydopamine is reported. The interconnected nanocages as the basic building unit of graphene sheets are assembled inside the skeletons of 3D graphene aerogels, leading to the 3D NPGA with well‐developed interconnected channels and the full exposure of electrochemically active sites. Benefiting from such an unique structure, the as‐made NPGA delivers a high specific capacity, an excellent rate capacity of 5978 mA h g^?1 at 3.2 A g^?1, and long cycle stability, especially at a large current density (54 cycles at 1 A g^?1), indicative of boosted rate capability and cycle life as air electrodes for Li–O₂ batteries. More importantly, based on the total mass of C+Li₂O₂, a gravimetric energy density of 2400 W h kg^?1 for the NPGA–O₂//Li cell is delivered at a power density of 1300 W kg^?1.     

Enhanced Optical Properties and Opaline Self‐Assembly of PPV Encapsulated in Mesoporous Silica Spheres

A new poly(p‐phenylenevinylene) (PPV) composite material has been developed by the incorporation of insoluble PPV polymer chains in the pores of monodisperse mesoporous silica spheres through an ion‐exchange and in situ polymerization method. The polymer distribution within the resultant colloidal particles is characterized by electron microscopy, energy dispersive X‐ray microanalysis, powder X‐ray diffraction, and nitrogen adsorption. It was found that the polymer was selectively incorporated into the mesopores of the silica host and was well distributed throughout the body of the particles. This confinement of the polymer influences the optical properties of the composite; these were examined by UV–vis and fluorescence spectroscopy and time‐correlated single‐photon counting. The results show a material that exhibits an extremely high fluorescence quantum yield (approaching 85%), and an improved resistance to oxidative photobleaching compared to PPV. These enhanced optical properties are further complemented by the overall processability of the colloidal material. In marked contrast to the insolubility of PPV, the material can be processed as a stable colloidal dispersion, and the individual composite spheres can be self‐assembled into opaline films using the vertical deposition method. The bandgap of the opal can be engineered to overlap with the emission band of the polymer, which has significant ramifications for lasing.     

Protein‐Release Behavior of Self‐Assembled PEG–β‐Cyclodextrin/PEG–Cholesterol Hydrogels

This paper reports on the degradation and protein release behavior of a self‐assembled hydrogel system composed of β‐cyclodextrin‐ (βCD) and cholesterol‐derivatized 8‐arm star‐shaped poly(ethylene glycol) (PEG₈). By mixing βCD‐ and cholesterol‐derivatized PEG₈ (molecular weights 10, 20 and 40 kDa) in aqueous solution, hydrogels with different rheological properties are formed. It is shown that hydrogel degradation is mainly the result of surface erosion, which depends on the network swelling stresses and initial crosslink density of the gels. This degradation mechanism, which is hardly observed for other water‐absorbing polymer networks, leads to a quantitative and nearly zero‐order release of entrapped proteins. This system therefore offers great potential for protein delivery.     

Highly Porous Polymer Aerogel Film‐Based Triboelectric Nanogenerators

A novel class of high performance polymer porous aerogel film‐based triboelectric nanogenerators (A‐NGs) is demonstrated. The A‐NGs, made of a pair of highly porous polymer films, exhibit much higher triboelectric outputs than the corresponding dense polymer film‐based triboelectric nanogenerators (D‐NGs) under the same mechanical stress. The triboelectric outputs of the A‐NGs increase significantly with increasing porosity, which can be attributed to the increase in contact area and the electrostatic induction in the porous structure, thereby leading to additional charges on the porous surface. Remarkably, the A‐NG fabricated using porous chitosan aerogel film paired with the most porous polyimide (with a porosity of 92%) aerogel film demonstrates a very high voltage of 60.6 V and current of 7.7 µA, corresponding to a power density of 2.33 W m^?2, which is sufficient to power 22 blue light‐emitting‐diodes (LEDs). This is the first report on triboelectric nanogenerators (TENGs) employing porous polymer aerogel films as both positive and negative materials to enhance triboelectric outputs. Furthermore, enhancing the tribopositive polarity of the cellulose aerogel film via silanization using aminosilane can dramatically improve the triboelectric performance. Therefore, this study provides new insights into investigating porous materials with tunable triboelectric polarities for high performance TENGs.     

Hemoglobin‐CdTe‐CaCO3@Polyelectrolytes 3D Architecture: Fabrication,Characterization, and Application in Biosensing

A Hemoglobin‐CdTe‐CaCO₃@polyelectrolyte 3D architecture is synthesized by a stepwise layer‐by‐layer method and is further used to fabricate an electrochemistry biosensor. While the calcium carbonate (CaCO₃) microsphere acts as an effective host for the loading of cadmium telluride (CdTe) quantum dots due to its channel‐like structure, the polyelectrolyte layers further increase the loading amount and help in the formation of a thick and uniform quantum‐dot “shell”, which not only improves the stability of the spheres in water, but also contributes to the fast and effective direct electron transfer between the protein redox center and the macroscopic electrode. The materials are characterized and compared, and the possible mechanism for the direct electrochemistry phenomenon is hypothesized. Our work not only provides a facile and effective route for the preparation of quantum‐dot‐loaded spheres, but also sets an example of how the structure of functional materials can be tuned and related to their applications. In addition, it is one of the few examples of using CaCO₃ microspheres in quantum‐dot loading and biosensing.     

Dual Electrostatic Assembly of Graphene Encapsulated Nanosheet‐Assembled ZnO‐Mn‐C Hollow Microspheres as a Lithium Ion Battery Anode

Graphene encapsulated nanosheet‐assembled ZnO‐Mn‐C hierarchical hollow microspheres are produced through a simple yet effective dual electrostatic assembly strategy, followed by a heating treatment in inert atmosphere. The modification of graphene sheets, metal Mn, and in situ carbon leads to form 3D interconnected conductive framework as electron highways. The hollow structure and the open configuration of hierarchical microspheres guarantee good structural stability and rapid ionic transport. More importantly, according to the density functional theory calculations, the oxygen vacancies in the hierarchical microspheres would cause an imbalanced charge distribution and thus the formation of local in‐plane electric fields around oxygen vacancy sites, which is beneficial for the ionic/electronic transport during cycling. Due to this multiscale coordinated design, the as‐fabricated graphene encapsulated nanosheet‐assembled ZnO‐Mn‐C hierarchical hollow microspheres demonstrate good lithium storage properties in terms of high reversible capacity (1094 mA h g^?1 at 100 mA g^?1), outstanding high‐rate long‐term cycling stability (843 mA h g^?1 after 1000 cycles at 2000 mA g^?1), and remarkable rate capability (422 mA h g^?1 after total 1600 cycles at 5000 mA g^?1).     

Porous Polymer Films with Gradient‐Refractive‐Index Structure for Broadband and Omnidirectional Antireflection Coatings

Porous polymer films that can be employed for broadband and omnidirectional antireflection coatings are successfully shown. These films form a gradient‐refractive‐index structure and are achieved by spin‐coating the solution of a polystyrene‐block‐poly(methyl methacrylate) (PS‐b‐PMMA)/PMMA blend onto an octadecyltrichlorosilane (OTS)‐modified glass substrate. Thus, a gradient distribution of PMMA domains in the vertical direction of the entire microphase‐separated film is obtained. After those PMMA domains are removed, a PS porous structure with an excellent gradient porosity ratio in the vertical direction of the film is formed. Glass substrates coated with such porous polymer film exhibit both broadband and omnidirectional antireflection properties because the refractive index increases gradually from the top to the bottom of the film. An excellent transmittance of >97% for both visible and near‐infrared (NIR) light is achieved in these gradient‐refractive‐index structures. When the incident angle is increased, the total transmittance for three different incident angles is improved dramatically. Meanwhile, the film possesses a color reproduction character in the visible light range.     

Inside Front Cover: One‐Pot Synthesis and Hierarchical Assembly of Hollow Cu2O Microspheres with Nanocrystals‐Composed Porous Multishell and Their Gas‐Sensing Properties (Adv. Funct. Mater. 15/2007)

On p. 2766, Qinshan Zhu and co‐workers report on multishell hollow Cu₂O microspheres that are synthesized by a facile and one‐pot solvothermal route. A two‐step organization process, in which hollow microspheres of Cu₂(OH)₃NO₃ are formed first followed by reduction to Cu₂O by glutamic acid, leads to the special multishell and hollow microstructures. Interestingly, a Cu₂O gas sensor fabricated with the multishell microspheres shows a much higher sensitivity to ethanol than solid Cu₂O microspheres. Hierarchical assembly of hollow microstructures is of great scientific and practical value and remains a great challenge. This paper presents a facile and one‐pot synthesis of Cu₂O microspheres with multilayered and porous shells, which were organized by nanocrystals. The time‐dependent experiments revealed a two‐step organization process, in which hollow microspheres of Cu₂(OH)₃NO₃ were formed first due to the Ostwald ripening and then reduced by glutamic acid, the resultant Cu₂O nanocrystals were deposited on the hollow intermediate microspheres and organized into finally multishell structures. The special microstructures actually recorded the evolution process of materials morphologies and microstructures in space and time scales, implying an intermediate‐templating route, which is important for understanding and fabricating complex architectures. The Cu₂O microspheres obtained were used to fabricate a gas sensor, which showed much higher sensitivity than solid Cu₂O microspheres.