A Hierarchical Janus Nanofibrous Membrane Combining Direct Osteogenesis and Osteoimmunomodulatory Functions for Advanced Bone Regeneration

An ideal guided bone regeneration membrane (GBRM) is expected not only to perform barrier function, but also to enhance osteogenesis and resist bacteria infection. However, currently available membranes have limited bioactivities. To address this challenge, a Janus GBRM (JGM) is designed and fabricated by sequential fractional electrospinning here. The random gelatin fibers loaded with hydroxyapatite (HAP) are designed as the inner face to promote the osteoblasts’ adhesion, proliferation, and osteogenic differentiation, meanwhile the aligned poly(caprolactone) (PCL) nanofibers loaded with poly(methacryloxyethyltrimethyl ammonium chloride-co-2-Aminoethyl 2-methylacrylate hydrochloride) (P(DMC-AMA)) are designed as the outer layer to resist epithelia invasion and bacterial infection. In vitro assays reveal that the inner face displays enhanced osteogenic effects, meanwhile the outer surface can regulate the epithelia to spread along the aligned direction and kill the contacted bacteria. Interestingly, the outer face can induce macrophages to polarize toward the M2 phenotype, thus manipulating a favorable osteoimmune environment. These results suggest that the JGM simultaneously meets the critical requirements of barrier, osteogenic, antibacterial, and osteoimmunomodulatory functions. Consequently, the JGM shows better in vivo bone tissue regeneration performance than the commercial Bio-Gide membrane. This work provides a novel platform to design multi-functional membranes/scaffolds, displaying great potential applications in tissue engineering.     

Multifunctional Modification of SIS Membrane with Chimeric Peptides to Promote Its Antibacterial,Osteogenic, and Healing-Promoting Abilities for Applying to GBR

Guided bone regeneration (GBR) technology is the most widely used and stable method for bone defect repair. However, infectious bone defect limits the application of this technique. Herein, a small intestinal submucosa (SIS) membrane modified by chimeric peptides as a new type of GBR membrane is developed for efficacious tissue regeneration. Based on the main components of SIS membrane are I and III collagen, collagen binding peptides TKKTLRT and KELNLVY sequences are used to construct chimeric peptides with healing-promoting peptide Hst1 or antibacterial osteogenic peptide JH8194, so as to realize the specifically target of SIS. This method achieves the fast and efficient multifunctional modification of SIS membrane. The chimeric peptides modified SIS (pSIS) membrane has satisfactory biocompatibility and a certain degree of antibacterial activity. Moreover, pSIS promotes the osteogenic related factors expression of rat bone mesenchymal stem cells and demonstrates great bone regeneration in rat skull defect model. Furthermore, pSIS accelerates the migration of oral epithelial cells in vitro and activate integrin α3β1 signal pathway contribute to wound healing. This study presents a novel biomaterial design of GBR membrane, specifically for the treatment of infectious bone defects.     

Multifunctional DNA Hydrogels with Hydrocolloid-Cotton Structure for Regeneration of Diabetic Infectious Wounds

Currently, diabetic infectious wound treatments remain a significant challenge for regenerative medicine due to the unicity of clinical dressings, which lack systemic multifunctional wound dressings with high absorbability, customizable shape, rapid self-healing, guiding tissue regeneration, and restoring physiological functions. Here, a multifunctional DNA hydrogel is conveniently obtained through grafting DNA units and polyethyleneimine dynamic cross-linking and doped heating function black phosphorus quantum dots. The obtained DNA hydrogel features excellent exudate absorption performance, adjustable heating ability, mechanical behavior, self-healing ability, writability, tissue adhesion, and antibacterial properties. The incorporation of procyanidin B2 (OPC B2) endows the DNA hydrogels with renowned scavenging free radicals and antioxidant properties. Furthermore, the DNA hydrogel dressing can promote the transformation of macrophages from pro-inflammatory M1 into repairing M2 phenotype, keeping the wound in a stable remodeled state. Astonishingly, the DNA hydrogel dressing can activate neurons to transform into a repair state, accelerating skin nerve regeneration and angiogenesis. Beyond that, it can recruit myeloid cells to activate the adaptive immune response, enhancing the ability of DNA hydrogel dressing to promote tissue regeneration, thereby promoting hair follicle and hair regeneration. Therefore, this advanced collaborative strategy provides an effective method for cascade management of clinical guided tissue regeneration.     

Oxygen Self-Sufficient Nanoplatform for Enhanced and Selective Antibacterial Photodynamic Therapy against Anaerobe-Induced Periodontal Disease

The hypoxic microenvironment, continuous oxygen consumption, and poor excitation light penetration depth during antimicrobial photodynamic therapy (aPDT) tremendously hinder the effects on bacterial inactivation. Herein, a smart nanocomposite with oxygen-self-generation is presented for enhanced and selective antibacterial properties against anaerobe-induced periodontal diseases. By encapsulating Fe₃O₄ nanoparticles, Chlorin e6 and Coumarin 6 in the amphiphilic silane, combined light (red and infrared) stimulated aPDT is realized due to the increased conjugate structure, the corresponding red-shifted absorption, and the magnetic navigation performance. To address the hypoxic microenvironment problem, further modification of MnO₂ nanolayer on the composites is carried out, and catalytical activity is involved for the decomposition of hydrogen peroxide produced in the metabolic processing, providing sufficient oxygen for aPDT in infection sites. Experiments in the cellular level and animal model proved that the rising oxygen content could effectively relieve the hypoxia in a periodontal pocket and enhance the ROS production, remarkably boosting aPDT efficacy. The increasing local level of oxygen also shows the selective inhibition of pathogenic and anaerobic bacteria, which determines the success of periodontitis treatment. Therefore, this finding is promising for combating anaerobic pathogens with enhanced and selective properties in periodontal diseases, even in other bacteria-induced infections, for future clinical application.     

Mechanically Strong and Multifunctional Hybrid Hydrogels with Ultrahigh Electrical Conductivity

Stretchable conductive hydrogels with simultaneous high mechanical strength/modulus, and ultrahigh, stable electrical conductivity are ideal for applications in soft robots, artificial skin, and bioelectronics, but to date, they are still very challenging to fabricate. Herein, sandwich-structured hybrid hydrogels based on layers of aramid nanofibers (ANFs) reinforced polyvinyl alcohol (PVA) hydrogels and a layer of silver nanowires (AgNWs)/PVA are fabricated by electrospinning combined with vacuum-assisted filtration. The hybrid ANF-PVA hydrogels exhibit excellent mechanical properties with the tensile modulus of 10.7–15.4 MPa, tensile strength of 3.3–5.5 MPa, and fracture energy up to 5.7 kJ m⁻², primarily attributed to the strong hydrogen bonding interactions between PVA and ANFs and in-plane alignment of the fibrous structure. Rational design of heterogeneous structure endows the hydrogels with ultrahigh apparent electrical conductivity of 1.66 × 10⁴ S m⁻¹, among the highest electrical conductivities ever reported so far for conductive hydrogels. More importantly, this ultrahigh conductivity remains constant upon a broad range of applied strains from 0–90% and over 500 stretching cycles. Furthermore, the hydrogels exhibit excellent Joule heating and electromagnetic interference shielding performances due to the ultrahigh electrical conductivity. These mechanically strong, hybrid hydrogels with ultrahigh and strain-invariant electrical conductivity represent great promises for many important applications such as flexible electronics.     

A Rubberlike Stretchable Fibrous Membrane with Anti‐Wettability and Gas Breathability

The fabrication of a stable, anti‐wetting surface is a very challenging issue in surface chemistry. In general, superhydrophobicity highly depends on the surface structure. Moreover, mechanical deformation of the surface structure can produce dramatic changes in the surface wetting state, and in some cases, may even result in a complete loss of the surface's unique wettability. However, the study of stable surfaces under mechanical deformation conditions has been limited to flexible surfaces or small strain. Here, a mechanically stable superhydrophobic membrane is presented, which possesses high stretchability and gas breathability. The membrane, which consists of an elastic polyurethane fibrous matrix coated with polyaniline hairy nanostructures and polytetrafluoroethylene, exhibites excellent superhydrophobic properties under ≥300% strain. The breathability and wettability of the membrane is examined by examining various static and dynamic wetting parameters. The robust membrane maintaines its anti‐wettability (water contact angle ≈160°, hysteresis ≈10°) for 1000 stretching cycles. It is also determined that the stretchable and superhydrophobic surface suppresses the fragmentation and rebound of impact droplets, compared with rigid superhydrophobic surfaces. Finally, underwater gas sensing is demonstrated as a novel application.     

Synthesis and Fabrication of Multifunctional Nanocomposites: Stable Dispersions of Nanoparticles Tethered with Short,Dense and Polydisperse Polymer Brushes in Poly(methyl methacrylate)

This paper presents a melt‐processable multifunctional nanocomposite material that shows highly controlled tunability in refractive index, glass transition temperature (T_g) and energy bandgap. ZnO quantum dots tethered with polymer brushes are melt‐blended into the matrix polymer, giving rise to multiple functionalities in the nanocomposites. Brush–matrix polymer interactions are important in determining the ability of polymer‐grafted nanoparticles to disperse in a polymer melt, of which graft density (σ), brush (N) and matrix (P) polymer lengths are the critical parameters. It is generally assumed that long polymer brushes (N > P) and an optimum graft density are necessary to achieve a good dispersion. Here it is demonstrated that nanoparticles tethered with short, dense and polydisperse polymer brushes via radical copolymerization can exhibit a stable, fine dispersion in the polymer melt. The quality of the dispersion of the nanoparticles is characterized by measuring physical properties that are sensitive to the state of the dispersion. This synthesis method presents a general approach for the inexpensive and high‐throughput fabrication of high quality, melt‐blendable nanocomposites that incorporate functional nanoparticles, paving the way for wider application of high performance nanocomposites.     

High Yield Electrosynthesis of Hydrogen Peroxide from Water Using Electrospun CaSnO3@Carbon Fiber Membrane Catalysts with Abundant Oxygen Vacancy

Hydrogen peroxide (H₂O₂) production by electrochemical two-electron water oxidation reaction (2e-WOR) is a promising approach, where high-performance electrocatalysts play critical roles. Here, the synthesis of nanostructured CaSnO₃ confined in conductive carbon fiber membrane with abundant oxygen vacancy (O_V) as a new generation of 2e-WOR electrocatalyst is reported. The CaSnO₃@carbon fiber membrane can be directly used as a self-standing electrode, exhibiting a record-high H₂O₂ production rate of 39.8 µmol cm⁻² min⁻¹ and a selectivity of ≈90% (at 2.9 V vs reversible hydrogen electrode). The CaSnO₃@carbon fiber membrane design improves not only the electrical conductivity and stability of catalysts but also the inherent activity of CaSnO₃. Density functional theory calculation further indicates the crucial role of O_V in increasing the adsorption free energy toward oxygen intermediates associated with the competitive four-electron water oxidation reaction pathway, thus enhancing the activity and selectivity of 2e-WOR. The findings pave a new avenue to the rational design of electrocatalysts for H₂O₂ production from water.     

A Multifunctional Coating Strategy for Promotion of Immunomodulatory and Osteo/Angio-Genic Activity

Building of multifunctional coatings in a more effective way is crucial for meeting the multilevel requirements of regenerative medicine. Herein, inspired by diatom and mussel, a specific but universal approach is proposed for building multifunctional coatings on slow-degradable and fast-degradable scaffolds or various substrates by using epigallocatechin gallate (EGCG) and polyethyleneimine (PEI) as bridges of silicon coupling. The results reveal that the polyphenol EGCG facilitates silica precipitation and coating topological morphology in synergy with PEI, and realizes antioxidant and immunomodulatory effects. The introduction of EGCG and the release of silicon ions present effective modulation of the immune microenvironment and remarkable promotion of angiogenesis and osteogenesis. The EGCG/silica coating strategy demonstrates a promising perspective for designing multifunctional coatings and optimizing tissue regeneration and reconstruction.     

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.     

Scalable Construction of Multifunctional Protection Layer with Low-Cost Water Glass for Robust and High-Performance Zinc Anode

Zinc ion batteries (ZIBs) have recently attracted tremendous interest for being low-cost, environmentally benign, and high energy density. However, the large-scale practical application of ZIBs is hampered by well-known undesirable dendrite growth and serious side reactions of the Zn anode during the long-term cycling process. Herein, a multifunctional water-glass artificial protection layer with enormous Si─O functional groups is constructed on Zn anode through a simple spin-coating method. The theoretical and experimental investigation suggests that the as-constructed interface with rich Si─O hydrophilic functional groups on Zn anode could facilitate the even distribution of electric field distribution and homogeneous wettability, navigate uniform zinc deposition/stripping along the (002) plane, and subsequently lead to well-suppressed dendrite growth and effective prohibition of oxygen-involved corrosion. Consequently, the water glass-modified anode achieves highly reversible Zn plating/stripping over 1500 h at a high current density of 10 mA cm⁻² in symmetrical cells, and a high capacity retention ratio of 79.4% at the current density of 5 A g⁻¹ in full cells paired with V₂O₅ cathode. This proposed water glass coating layer design is cheap, up-scalable, and facile, which could substantially accelerate the rapid commercialization of zinc anodes and unleash the full potential of renewable ZIBs for next-generation large-scale energy storage.     

A General Strategy to Fabricate Flexible Oxide Ceramic Nanofibers with Gradient Bending-Resilience Properties

Inorganic materials assembled with rigid elements such as crystals or graphitized carbon generally show brittleness and hardness. However, it is found that both TiO₂ ceramic crystal nanofibers (NFs) and carbon NFs show superior flexibility, in which the former are surprisingly knottable and the latter exhibit excellent bending-resilience property. The different flexure mechanisms are revealed by fabricating composite NFs of these two constituents and find that the carbon NFs can be recovered to the original states after releasing the external force, while the bending-resilience is weakened and the softness of the composite NFs is enhanced upon increasing the TiO₂ content. The graphitized carbon can store mechanical deformation energy that enables the NFs with bending-resilience, while both the homogeneous interfaces between TiO₂ crystals and the heterogeneous interfaces between TiO₂ and carbon can alleviate stress concentration, which reduce the flexural modulus of the composite NFs. By filling different contents of elastic carbon into TiO₂ NFs, a series of flexible NFs that exhibit gradient bending-resilience properties are fabricated. This study provides a deeper understanding of the mechanical properties of inorganic materials.     

Comparison of organic photovoltaic with graphene oxide cathode and anode buffer layers

In this report, we present inverted organic solar cells integrating solution-processed aluminum doped zinc oxide (AZO) and trilayer graphene oxide (GO) as an electron selective and anode buffer layers, respectively. The polymers in this inverted architecture are PCDTBT, PBDTTPD and PCBM as an electron donor and acceptor, respectively and the photovoltaic performance were recorded at 300 K under 100 mW/cm² light intensity. The characteristics of PCDTBT and PBDTTPD-based inverted solar cells were: open-circuit voltages (V_oc’s) 0.74 and 0.70 V, short-circuit current densities (J_sc’s) −12.09 and −12.06 mA/cm², fill factors (FFs) of 60.73% and 60.03%, with an overall power conversion efficiencies (PCEs) of about 5.46% and 5.07%. The fabricated inverted cells show better performances compared to conventional structure reference cells.     

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.     

Lineage‐Specific Commitment of Stem Cells with Organic and Graphene Oxide–Functionalized Nanofibers

Controlling the differentiation to certain lineages is the main goal of current stem cell research, which might exploit new routes based on the interaction of cells with nanomaterials. Here it is shown that primary neurospheres from dental pulp stem cells grown on combinatorial surfaces with different fibrous morphology and graphene oxide functionalization exhibit different differentiation propensity. The developed materials strongly influence the stem cell fate, as highlighted by morphological, immunofluorescence, molecular biology, and functional analyses. Instructive cues lead to the increased expression of markers that are characteristic of selective differentiation into osteoblasts, glial cells, fibroblasts, and neurons even in basal medium conditions, and randomly oriented fibers are found to revert neuronal precommitment and to trigger osteoblastic differentiation. Graphene oxide coatings lead instead to the relatively enhanced expression of genes typical of either glial or neuronal commitment, depending on the underlying nanofibrous morphology. The mechanisms addressing cell fate are investigated, highlighting the correlation of wetting anisotropy and protein adsorption capacity of different surfaces, ultimate cell conformational changes reflected by skeletal and nuclear elongation, and directed cell commitment. Cues from the different surfaces are therefore lineage‐specific, unveiling remarkable potentialities for cellular programming by means of nanomaterials.     

Aligned PCL Fiber Conduits Immobilized with Nerve Growth Factor Gradients Enhance and Direct Sciatic Nerve Regeneration

Topographical guidance and chemotaxis are crucial factors for peripheral nerve regeneration. This study describes the preparation of highly aligned poly(ε‐caprolactone) (PCL) fiber conduits coated with a concentration gradient of nerve growth factor (NGF) (A/G‐PCL) using a newly designed electrospinning receiving device. The A/G‐PCL conduits are confirmed in vitro to enhance and attract the neurite longitudinal growth of dorsal root ganglion (DRG) neurons toward their high‐concentration gradient side. In vivo, the A/G‐PCL conduits are observed to direct a longitudinal stronger attraction of axons and migration of Schwann cells in 15 mm rat sciatic nerve defects. At 12 weeks, rats transplanted with A/G‐PCL conduits show satisfactory morphological and functional improvements in g‐ratio, total number, and area of myelinated nerve fibers as well as the sciatic function index, compound muscle action potentials, and muscle wet weight ratio as compared to aligned PCL fibers conduits with uniform NGF (A/U‐PCL). The performance of A/G‐PCL is similar to that of autografts. Moreover, mRNA‐seq and RT‐PCR results reveal that Rap1, MAPK, and cell adhesion molecules signaling pathways are closely associated with axon chemotactic response and attraction. Altogether, by combining structural guidance with axon chemotaxis, the NGF‐gradient/aligned PCL fiber conduits represent a promising approach for peripheral nerve defect repair.     

Nanofibrous Composite with Tailorable Electrical and Mechanical Properties for Cardiac Tissue Engineering

Cardiac tissue engineering is a promising strategy to prevent functional deterioration or even to enhance cardiac function upon myocardial infarction. Here, electrospun fiber mats containing different combinations of electrically conductive polyaniline, collagen, and/or hyaluronic acid are assessed regarding material properties and compatibility with cardiomyocyte attachment and function. Microstructure analysis reveals that collagen fiber mats contain a wide range of fiber diameters after crosslinking (from ≈300 nm to ≈5 µm); all other fiber mats contain fibers in the range of ≈120 to ≈300 nm. Fiber mats exhibit comparable electrical conductivity to and greater mechanical properties than the native human myocardium, which is considered beneficial. Cell–matrix interaction analysis utilizing postnatal rat cardiomyocytes reveals that the fiber mats are non‐cytotoxic and permit cell attachment and contraction. Fiber mats containing collagen (9.89%), hyaluronic acid (1.1%), and polyaniline (PANi, 1.34%) exhibit the most favorable properties with longer contraction time, higher contractile amplitude, and lower beating rates. Improved contraction is accompanied by increased connexin 43 expression. Importantly, this fiber mat is a suitable material for human‐induced pluripotent stem cell–derived cardiomyocytes regarding cytotoxicity, cell attachment, and function. Collectively, these data demonstrate that fiber mats made of collagen, hyaluronic acid, and polyaniline are promising materials for cardiac tissue engineering.     

Four Birds with One Stone: A Multifunctional Polypeptide Nanocomposite to Unify Ferroptosis,Nitric Oxide,and Photothermia for Amplifying Antitumor Immunity

Tumor metastasis and relapse mainly results in therapy failure and becomes a big challenge in oncology. Immunogenic cell death (ICD) of tumors mediated immunotherapy (IT) is attracting widely for solving that problem although achieving sufficient ICD and strong immune response is challenging for nanoparticles-based cancer IT. Herein, a multifunctional polypeptide coordinate nanocomposite that possesses near infrared photothermia (PT) and responsive releases of nitric oxide (NO) and iron ions is constructed, which synergistically kills cancer cells and highly prohibits metastatic 4T1 cells invasion and migration by PT-boosted NO release and ferroptosis (FT). Remarkably, triple FT-NO-PT treatment amplifies the ICD effects and outperforms combo/monotherapy FT-PT and FT in cancer cells and tumors, which further activates dendritic cells maturation, and primed CD4⁺T and CD8⁺T cells immune responses and memory effects, playing four birds with one stone (i.e., FT-NO-PT-IT). The PCSFG-based FT-NO-PT not only fully eradicates 4T1 primary tumors, but also induces strong ICD, immune priming, and memory effects to reject rechallenged 4T1 tumors and inhibit malignant tumor metastasis, demonstrating synergistic amplified ICD effects with strong cell immunities and memory effects by a unified FT-NO-PT-IT.