Magnesium Gradient-Based Hierarchical Scaffold for Dual-Lineage Regeneration of Osteochondral Defect

Osteochondral regeneration remains a great challenge due to the limited self-healing ability and the complexity of its hierarchical structure and composition. Mg²⁺ and hypoxia are two effective modulators in boosting chondrogenesis. To this end, a double-layered scaffold (D) consisting of a hydrogel layer on a porous cryogel is fabricated to mimic the hierarchical structure of osteochondral tissue. An Mg²⁺ gradient is incorporated into the double-layered scaffold with hypoxia-mimicking deferoxamine (DFO) embedded in the hydrogel (D-Mg-DFO), which remarkably augments the dual-lineage regeneration of both cartilage and subchondral bone. The higher Mg²⁺ supplementation from the upper hydrogel, associated with its hypoxia-mimicking situation and small pore size, exhibits promotive effects on chondrogenic differentiation. The lower Mg²⁺ supplementation from the bottom cryogel, associated with its interconnected macroporous structure, achieves multiple contributions in stem cell migration from bone marrow cavity, matrix mineralization, and osteogenesis. Furthermore, rabbits’ trochlea osteochondral defects are established to evaluate the regenerative outcome. Compared to control scaffolds containing only Mg²⁺ or DFO, the D-Mg-DFO scaffold presents the best regenerative effect under the synergistic contribution of multiple factors. Overall, this work provides a new design of scaffold toward an effective repair of cartilage defect.     

Integrated and Bifunctional Bilayer 3D Printing Scaffold for Osteochondral Defect Repair

Bioinspired scaffolds with two distinct regions resembling stratified anatomical architecture provide potential strategies for osteochondral defect repair and are studied in preclinical animals. However, delamination of the two layers often causes tissue disjunction between the regenerated cartilage and subchondral bone, leading to few commercially available clinical applications. This study develops an integrated poly(ε-caprolactone) (PCL)-based scaffold for repairing osteochondral defects. An extracellular matrix (ECM)-incorporated 3D printing composite scaffold (ECM/PCL) coated with ECM hydrogel (E-co-E/PCL) is fabricated as the upper layer, and magnesium oxide nanoparticles coated with polydopamine (MgO@PDA)-incorporated composite scaffold (MD/PCL) is fabricated using 3D printing as the bottom layer. The physicochemical and mechanical properties of the bilayer scaffold meet the requirements in designing and fabricating the osteochondral scaffold, especially a strong interface possessed between the two layers. By in vitro study, the integrated scaffold stimulates proliferation, chondrogenic differentiation, and osteogenic differentiation of human bone mesenchymal stem cells. Moreover, the integrated bilayer scaffold exhibits well repair ability to facilitate simultaneous regeneration of cartilage and subchondral bone after implanting into the osteochondral defect in rats. In addition, cartilage “tidemarks” completely regenerated after 12 weeks of implantation of the bilayer scaffold, which indicates no tissue disjunctions formed between the regenerated cartilage and subchondral bone.     

Direct 3D Printing of High Strength Biohybrid Gradient Hydrogel Scaffolds for Efficient Repair of Osteochondral Defect

The emerging 3D printing technique allows for tailoring hydrogel‐based soft structure tissue scaffolds for individualized therapy of osteochondral defects. However, the weak mechanical strength and uncontrollable swelling intrinsic to conventional hydrogels restrain their use as bioinks. Here, a high‐strength thermoresponsive supramolecular copolymer hydrogel is synthesized by one‐step copolymerization of dual hydrogen bonding monomers, N‐acryloyl glycinamide, and N‐[tris(hydroxymethyl)methyl] acrylamide. The obtained copolymer hydrogels demonstrate excellent mechanical properties—robust tensile strength (up to 0.41 MPa), large stretchability (up to 860%), and high compressive strength (up to 8.4 MPa). The rapid thermoreversible gel ? sol transition behavior makes this copolymer hydrogel suitable for direct 3D printing. Successful preparation of 3D‐printed biohybrid gradient hydrogel scaffolds is demonstrated with controllable 3D architecture, owing to shear thinning property which allows continuous extrusion through a needle and also immediate gelation of fluid upon deposition on the cooled substrate. Furthermore, this biohybrid gradient hydrogel scaffold printed with transforming growth factor beta 1 and β‐tricalciumphosphate on distinct layers facilitates the attachment, spreading, and chondrogenic and osteogenic differentiation of human bone marrow stem cells (hBMSCs) in vitro. The in vivo experiments reveal that the 3D‐printed biohybrid gradient hydrogel scaffolds significantly accelerate simultaneous regeneration of cartilage and subchondral bone in a rat model.     

3D Molecularly Functionalized Cell‐Free Biomimetic Scaffolds for Osteochondral Regeneration

Clinically, cartilage damage is frequently accompanied with subchondral bone injuries caused by disease or trauma. However, the construction of biomimetic scaffolds to support both cartilage and subchondral bone regeneration remains a great challenge. Herein, a novel strategy is adopted to realize the simultaneous repair of osteochondral defects by employing a self‐assembling peptide hydrogel (SAPH) FEFEFKFK (F, phenylalanine; E, glutamic acid; K, lysine) to coat onto 3D‐printed polycaprolactone (PCL) scaffolds. Results show that the SAPH‐coated PCL scaffolds exhibit highly improved hydrophilicity and biomimetic extracellular matrix (ECM) structures compared to PCL scaffolds. In vitro experiments demonstrate that the SAPH‐coated PCL scaffolds promote the proliferation and osteogenic differentiation of rabbit bone mesenchymal stem cells (rBMSCs) and maintain the chondrocyte phenotypes. Furthermore, 3% SAPH‐coated PCL scaffolds significantly induce simultaneous regeneration of cartilage and subchondral bone after 8‐ and 12‐week implantation in vivo, respectively. Mechanistically, by virtue of the enhanced deposition of ECM in SAPH‐coated PCL scaffolds, SAPH with increased stiffness facilitates and remodels the microenvironment around osteochondral defects, which may favor simultaneous dual tissue regeneration. These findings indicate that the 3% SAPH provides efficient and reliable modification on PCL scaffolds and SAPH‐coated PCL scaffolds appear to be a promising biomaterial for osteochondral defect repair.     

3D Superelastic Scaffolds Constructed from Flexible Inorganic Nanofibers with Self‐Fitting Capability and Tailorable Gradient for Bone Regeneration

Repair of bone defects with irregular shapes or at soft tissue insertion sites faces a huge challenge. Scaffolds capable of adapting to bone cavities, generating stiffness gradients, and inducing osteogenesis are necessary. Herein, a superelastic 3D ceramic fibrous scaffold is developed by assembly of intrinsically rigid, structurally flexible electrospun SiO₂ nanofibers with chitosan as bonding sites (SiO₂ NF‐CS) via a lyophilization technique. SiO₂ NF‐CS scaffolds exhibit excellent elasticity (full recovery from 80% compression), fast recovery rate (>500 mm min^?1), and good fatigue resistance (>10 000 cycles of compression) in an aqueous medium. SiO₂ NF‐CS scaffolds induce human mesenchymal stem cell (hMSC) elongation and differentiation into osteoblasts. In vivo self‐fitting capability is demonstrated by implanting compressed SiO₂ NF‐CS scaffolds into different shaped mandibular defects in rabbits, with a spontaneous recovery and full filling of defects. Rat calvarial defect repair validates enhanced bone formation and vascularization by cell (hMSC) histomorphology analysis. Further, subchondral bone scaffolds with gradations in SiO₂ nanofibers are developed, leading to a stiffness gradient and spatially chondrogenic and osteogenic differentiation of hMSCs. This work presents a type of 3D ceramic fibrous scaffold, which can closely match bone defects with irregular shapes or at different implant sites, and is promising for clinical translation.     

Phase-Separated Polyzwitterionic Hydrogels with Tunable Sponge-Like Structures for Stable Solar Steam Generation

Solar steam generation (SSG) through hydrogel-based evaporators has shown great promise for freshwater production. However, developing hydrogel-based evaporators with stable SSG performance in high-salinity brines remains challenging. Herein, phase-separated polyzwitterionic hydrogel-based evaporators are presented with sponge-like structures comprising interconnected pores for stable SSG performance, which are fabricated by photopolymerization of sulfobetaine methacrylate (SBMA) in water-dimethyl sulfoxide (DMSO) mixed solvents. It is shown that driven by competitive adsorption, the structures of the resulting poly(sulfobetaine methacrylate) (PSBMA) hydrogels can be readily tuned by the volume ratio of DMSO to achieve phase separation. The optimized phase-separated PSBMA hydrogels, combining the unique anti-polyelectrolyte effects of polyzwitterionic hydrogels, demonstrate a rapid water transport capability in brines. After introducing photothermal polypyrrole particles on the surface of the phase-separated PSBMA hydrogel evaporators, a stable water evaporation rate of ≈2.024 kg m⁻² h⁻¹ and high solar-to-vapor efficiency of ≈97.5% in a 3.5 wt.% brine are obtained under simulated solar light irradiation (1.0 kW m⁻²). Surprisingly, the evaporation rates remain stable even under high-intensity solar irradiation (2.0 kW m⁻²). It is anticipated that the polyzwitterionic hydrogel evaporators with sponge-like porous structures will contribute to developing SSG technology for high-salinity seawater applications.     

3D Printing of Bilineage Constructive Biomaterials for Bone and Cartilage Regeneration

Owing to the different biological properties of articular cartilage and subchondral bone, it remains significant challenge to construct a bi‐lineage constructive scaffold. In this study, manganese (Mn)‐doped β‐TCP (Mn‐TCP) scaffolds with varied Mn contents are prepared by a 3D‐printing technology. The effects of Mn on the physicochemical properties, bioactivity, and corresponding mechanism for stimulating osteochondral regeneration are systematically investigated. The incorporation of Mn into β‐TCP lowers the lattices parameters and crystallization temperatures, but improves the scaffold density and compressive strength. The ionic products from Mn‐TCP significantly improve the proliferation of both rabbit chondrocytes and mesenchymal stem cells (rBMSCs), as well as promote the differentiation of chondrocytes and rBMSCs. The in vivo study shows that Mn‐TCP scaffolds distinctly improve the regeneration of subchondral bone and cartilage tissues as compared to TCP scaffolds, upon transplantation in rabbit osteochondral defects for 8 and 12 weeks. The mechanism is closely related to the Mn²⁺ ions significantly stimulated the proliferation and differentiation of chondrocytes through activating HIF pathway and protected chondrocytes from the inflammatory osteoarthritis environment by activating autophagy. These findings suggest that 3D‐printing of Mn‐containing scaffolds with improved physicochemical properties and bilineage bioactivities represents an intelligent strategy for regenerating osteochondral defects.     

Thermochemotherapy Meets Tissue Engineering for Rheumatoid Arthritis Treatment

Rheumatoid arthritis (RA) is an autoimmune disease that progresses from inflammation to cartilage destruction. Inspired by the similar characteristics of inflammatory granulation tissue to those of tumors, the newly emerged tumor therapy called thermochemotherapy is proposed to treat RA. Meanwhile, the repair of cartilage injury via tissue engineering is paid attention simultaneously. A first-line antirheumatic drug (MTX; methotrexate) and transforming growth factor β1 (TGF-β1) are loaded in nano-Fe₃O₄ composite chitosan-polyolefin to construct a multifunctional hydrogel (DN-Fe-MTX-TGFβ1). The mechanical properties of the hydrogel are equivalent to that of articular cartilage to guarantee its role as a scaffold. A long-term release ability and the magnetocaloric properties of the hydrogel assure its effect to provide sustained local thermochemotherapy. The effective ability of the hydrogel for both anti-inflammation and cartilage repair is demonstrated. This work indicates a promising way to combine thermochemotherapy and tissue engineering for the effective treatment of RA for the first time.     

Injectable,Self-Contained,Subaqueously Cross-Linking Laminous Adhesives for Biophysical-Chemical Modulation of Osteochondral Microenvironment

Current osteochondral (OC) defect repair approaches using premade scaffolds face clinical limitations due to invasiveness, weak integrity, and/or insufficient interfacial bonding. An injectable hydrophobic laminous adhesive is developed that rapidly photocross-link subaqueously and forms robust bi-layered structure that orchestrates biophysical-chemical cues for stimulating OC repair. Liquid hydrophobic photo-cross-linkable poly (lactide-co-propylene glycol-co-lactide) dimethacrylates (P_mL_nDMA) are adopted as cartilage phase and P_mL_nDMA encapsulating methacrylated hydroxyapatite nanoparticles (P_mL_nDMA/MH) as the mineralized subchondral bone phase. Both phases exhibit strong interfacial bonding due to the presence of “CC”. Mechanotransduction and growth factor-mediated signaling pathways are enchanced by matching the mechanical properties of two phases to native cartilage and bone via systematical modulation of the adhesives’ composition and encapsulated growth factors’ release profile. This enhances mesenchymal stem cells’ commitment to corresponding chondrocytes and osteoblasts to augment OC repair in vitro and in vivo, and ultimately benefits patients suffering from OC fracture, osteoarthritis, and osteoporosis.     

Large Cumulative Capacity Enabled by Regulating Lithium Plating with Metal–Organic Framework Layers on Porous Carbon Nanotube Scaffolds

The high specific capacity of lithium metal is ideal to meet the current demand in rechargeable batteries but lithium dendrites and irreversible volume expansions are major hurdles. 3D lithium host materials can alleviate these problems by lowering the current density with large surface areas and accommodating lithium metal in their pores. However, lithium dendrites are persistently observed because of sluggish lithium-ion diffusion through tortuous pores, resulting in clogging and thereby dendrite growth. Herein, layered metal–organic frameworks (MOFs) are deposited on carboxylated carbon nanotube (CNT) scaffolds via coordination bonding. The MOF layer on the outside of the CNT scaffold has augmented lithium insertion into the porous scaffolds (24 mAh cm⁻² at 8 mA cm⁻²) and lithium plating/stripping lifetime (over 1700 h with 20 mAh cm⁻² cycle⁻¹). MOF has pores large enough for lithium ions to permeate through, and its electronically insulating property creates capacitive effects, distributing lithium ions over the surface of the MOF layer to avoid dendrite growth and clogging during lithium plating. Outstanding volumetric and gravimetric capacities (≈940 mAh cm⁻³ and ≈980 mAh g⁻¹) along with exceptional cumulative capacity (≈4.9 Ah cm⁻²) are obtained. This promising approach can store lithium without dendrites to deliver high energy densities required for the current rechargeable batteries.     

A Bi‐Lineage Conducive Scaffold for Osteochondral Defect Regeneration

Because cartilage and bone tissues have different lineage‐specific biological properties, it is challenging to fabricate a single type of scaffold that can biologically fulfill the requirements for regeneration of these two lineages simultaneously within osteochondral defects. To overcome this challenge, a lithium‐containing mesoporous bioglass (Li‐MBG) scaffold is developed. The efficacy and mechanism of Li‐MBG for regeneration of osteochondral defects are systematically investigated. Histological and micro‐CT results show that Li‐MBG scaffolds significantly enhance the regeneration of subchondral bone and hyaline cartilage‐like tissues as compared to pure MBG scaffolds, upon implantation in rabbit osteochondral defects for 8 and 16 weeks. Further investigation demonstrates that the released Li+ ions from the Li‐MBG scaffolds may play a key role in stimulating the regeneration of osteochondral defects. The corresponding mechanistic pathways involve Li+ ions enhancing the proliferation and osteogenic differentiation of bone mesenchymal stem cells (BMSCs) through activation of the Wnt signalling pathway, as well as Li+ ions protecting chondrocytes and cartilage tissues from the inflammatory osteoarthritis (OA) environment through activation of autophagy. These findings suggest that the incorporation of Li+ ions into bioactive MBG scaffolds is a viable strategy for fabricating bi‐lineage conducive scaffolds that enhance regeneration of osteochondral defects.     

A Self-Thickening and Self-Strengthening Strategy for 3D Printing High-Strength and Antiswelling Supramolecular Polymer Hydrogels as Meniscus Substitutes

3D printing of high-strength and antiswelling hydrogel-based load-bearing soft tissue scaffolds with similar geometric shape to natural tissues remains a great challenge owing to insurmountable trade-off between strength and printability. Herein, capitalizing on the concentration-dependent H-bonding-strengthened mechanism of supramolecular poly(N-acryloyl glycinamide) (PNAGA) hydrogel, a self-thickening and self-strengthening strategy, that is, loading the concentrated NAGA monomer into the thermoreversible low-strength PNAGA hydrogel is proposed to directly 3D printing latently H-bonding-reinforced hydrogels. The low-strength PNAGA serves to thicken the concentrated NAGA monomer, affording an appropriate viscosity for thermal-assisted extrusion 3D printing of soft PNAGA hydrogels bearing NAGA monomer and initiator, which are further polymerized to eventually generate high-strength and antiswelling hydrogels, due to the reconstruction of strong H-bonding interactions from postcompensatory PNAGA. Diverse polymer hydrogels can be printed with self-thickened corresponding monomer inks. Further, the self-thickened high-strength PNAGA hydrogel is printed into a meniscus, which is implanted in rabbit's knee as a substitute with in vivo outcome showing an appealing ability to efficiently alleviate the cartilage surface wear. The self-thickening strategy is applicable to directly printing a variety of polymer-hydrogel-based tissue engineering scaffolds without sacrificing mechanical strength, thus circumventing problems of printing high-strength hydrogels and facilitating their application scope.     

Polymer Fiber Scaffolds for Bone and Cartilage Tissue Engineering

Successful regeneration of weight‐bearing bone defects and critical‐sized cartilage defects remains a major challenge in clinical orthopedics. In the past decades, biodegradable polymer materials with biomimetic chemical and physical properties have been rapidly developed as ideal candidates for bone and cartilage tissue engineering scaffolds. Due to their unique advantages over other materials of high specific‐surface areas, suitable mechanical strength, and tailorable characteristics, scaffolds made of polymer fibers have been increasingly used for the repair of bone and cartilage defects. This Review summarizes the preparation and compositions of polymer fibers, as well as their characteristics. More importantly, the applications of polymer fiber scaffolds with well‐designed structures or unique properties in bone, cartilage, and osteochondral tissue engineering have been comprehensively highlighted. On the whole, such a comprehensive summary affords constructive suggestions for the development of polymer fiber scaffolds in bone and cartilage tissue engineering.     

A Diagnostic and Therapeutic Hydrogel to Promote Vascularization via Blood Sugar Reduction for Wound Healing

Chronic hyperglycemic damage is a major problem that undermines diabetic wound healing. By combining treatment and diagnosis together, blood glucose concentration can be monitored real-time through medical imaging devices and precise interventions can be carried out at the right time to promote diabetic wound repair. In this study, an injectable self-healing hyaluronic acid hydrogel is constructed using Schiff base reaction, and nanoenzymes (GOx-MnO₂) synthesized by condensation reaction, along with vascular endothelial growth factor (VEGF)-nanobubbles produced by double emulsification method, are loaded into the hydrogel, thus constructing an innovative diagnostic and therapeutic hydrogel system (US@GOx@VEGF hydrogel, UGV hydrogel). While monitoring glucose concentration in real-time, the system delivers VEGF through ultrasound in a precise and noninvasive way to deplete glucose. The UGV hydrogel integrates both processes of diagnosis and treatment, effectively releases VEGF through blasts triggered by ultrasound. Apart from this, this new trauma patch is capable of monitoring Mn²⁺ values ranging from 0.5 m to 7.8 × 10⁻³ m and glucose levels from 100 × 10⁻³ to 3 × 10⁻³ m , through magnetic resonance imaging. In summary, the hydrogel realizes real-time monitoring of glucose level, maintains glucose homeostasis through noninvasive intervention, and rapidly promotes the repair of diabetic skin defects, opening up a new path for chronic wound management.     

A Bifunctional Biomaterial with Photothermal Effect for Tumor Therapy and Bone Regeneration

Malignant bone tumor is one of the major bone diseases. The treatment of such a bone disease typically requires the removal of bone tumor and regeneration of tumor‐initiated bone defects simultaneously. To address this issue, it is required that implanted biomaterials should combine the bifunctions of both therapy and regeneration. In this work, a bifunctional graphene oxide (GO)‐modified β‐tricalcium phosphate (GO‐TCP) composite scaffold combining a high photothermal effect with significantly improved bone‐forming ability is prepared by 3D‐printing and surface‐modification strategies. The prepared GO‐TCP scaffolds exhibit excellent photothermal effects under the irradiation of 808 nm near infrared laser (NIR) even at an ultralow power density of 0.36 W cm^?2, while no photothermal effects are observed for pure β‐TCP scaffolds. The photothermal temperature of GO‐TCP scaffolds can be effectively modulated in the range of 40–90 °C by controlling the used GO concentrations, surface‐modification times, and power densities of NIR. The distinct photothermal effect of GO‐TCP scaffolds induces more than 90% of cell death for osteosarcoma cells (MG‐63) in vitro, and further effectively inhibits tumor growth in mice. Meanwhile, the prepared GO‐TCP scaffolds possess the improved capability to stimulate the osteogenic differentiation of rabbit bone mesenchymal stem cells (rBMSCs) by upregulating bone‐related gene expression, and significantly promote new bone formation in the bone defects of rabbits as compared to pure β‐TCP scaffolds. These results successfully demonstrate that the prepared GO‐TCP scaffolds have bifunctional properties of photothermal therapy and bone regeneration, which is believed to pave the way to design and fabricate novel implanting biomaterials in combination of therapy and regeneration functions.     

Zwitterionic Gradient Double-Network Hydrogel Membranes with Superior Biofouling Resistance for Sustainable Osmotic Energy Harvesting

Developing ion-selective membranes with anti-biofouling property and biocompatibility is highly crucial in harvesting osmotic energy in natural environments and for future biomimetic applications. However, the exploration of membranes with these properties in osmotic energy conversion remain largely unaddressed. Herein, a tough zwitterionic gradient double-network hydrogel membrane (ZGDHM) with excellent biofouling resistance and cytocompatibility for sustainable osmotic energy harvesting is demonstrated. The ZGDHM, composed of negatively charged 2-acrylamido-2-methylpropanesulfonic acid (AMPS) as the first scaffold network and zwitterionic sulfobetaine acrylamide (SBAA) as the second network, is prepared by a two-step photopolymerization, thus creating continuous gradient double-network nanoarchitecture and then remarkably enhanced mechanical properties. As verified by the experiments and simulations, the gradient nanoarchitecture endows the hydrogel membrane with apparent ionic diode effect and space-charge-governed transport property, thus facilitating directional ion transport. Consequently, the ZGDHM can achieve a power density of 5.44 W m⁻² by mixing artificial seawater and river water, surpassing the commercial benchmark. Most importantly, the output power can be promoted to an unprecedented value of 49.6 W m⁻² at the mixing of salt-lake water and river water, nearly doubling up most of the existing nanofluidic membranes. This study paves a new avenue toward developing ultrahigh-performance osmotic energy harvesters for biomimetic applications.     

Injectable In Situ Induced Robust Hydrogel for Photothermal Therapy and Bone Fracture Repair

Malignant bone tumors are often accompanied by osteolytic destruction and severe pathological fractures. Current therapeutic strategies can largely inhibit tumor proliferation, but the high recurrence rate of tumors and related bone defects remain a significant challenge. This study aims to address these issues by developing a novel near-infrared (NIR) light-responsive and a mechanically strong hydrogel that offers excellent photothermal tumor therapy and bone fracture repair capabilities. The as-prepared hydrogel exhibits good biocompatibility and an ultra-strong photothermal effect due to the formation of a complex network with up-conversion lanthanide-Au hybrid nanoparticles and alginate molecules. A subcutaneous tumor model is used to demonstrate that tumors can be efficiently eradicated via local photothermal treatment, where there is no tumor recurrence within the observation period. Moreover, the injected hydrogel becomes mechanically strong due to in situ Ca²⁺ crosslinking, which provides a supportive matrix to promote the repair of bone defects via stabilization of the fractured bone structure. The high photothermal effect and robust support offered by this single material demonstrate the potential of using the proposed hydrogel for the simultaneous treatment of bone tumor removal and bone healing.     

4D Printing of Multi-Responsive Membrane for Accelerated In Vivo Bone Healing Via Remote Regulation of Stem Cell Fate

Dynamic regulation of substrate micro-structures is an effective strategy to control stem cell fate in tissue engineering. Translating this into in vivo tissue repair in a clinical setting remains challenging, which requires precise temporal control of multi-scale structural features. Using 4D printing technique, a multi-responsive bilayer morphing membrane consisting of a shape memory polymer (SMP) layer and a hydrogel layer, is fabricated. The SMP layer is featured with responsive surface micro-structures, which can switch the phase between proliferation and differentiation precisely, thus promoting the bone formation. The hydrogel layer endows the membrane with the ability to digitally regulate its 3D geometry, matching the specific macroscopic bone shape in clinical scenario. The authors’ in vivo experiments show that the 4D shape-shifting membrane exhibits over 30% improvement in new bone formation in comparison to a reference membrane with static micro-structure. More importantly, the 4D membrane can conformally wrap a bone defect model in a non-invasive way and this strategy can be extended to repairs involving complex tissue defects.     

3D Printed Enzyme-Functionalized Scaffold Facilitates Diabetic Bone Regeneration

Patients with diabetes mellitus (DM) suffer from a high risk of fractures and poor bone healing ability. Surprisingly, no effective therapy is available to treat diabetic bone defect in clinic. Here, a 3D printed enzyme-functionalized scaffold with multiple bioactivities including osteogenesis, angiogenesis, and anti-inflammation in diabetic conditions is proposed. The as-prepared multifunctional scaffold is constituted with alginate, glucose oxidase (GOx), and catalase-assisted biomineralized calcium phosphate nanosheets (CaP@CAT NSs). The GOx inside scaffolds can alleviate the hyperglycemia environment by catalyzing glucose and oxygen into gluconic acid and hydrogen peroxide (H₂O₂). Both the generated H₂O₂ as well as the overproduced H₂O₂ in DM can be scavenged by CaP@CAT NSs, while the initiated hypoxic microenvironment stimulates neovascularization. Moreover, the incorporation of CaP@CAT NSs not only enhance the mechanical property of the scaffolds, but also facilitate bone regeneration by the degraded Ca²⁺ and PO₄³⁻ ions. The remarkable in vitro and in vivo outcomes demonstrate that enzymes functionalized scaffolds can be an effective strategy for enhancing bone tissue regeneration in diabetic conditions, underpinning the potential of multifunctional scaffolds for diabetic bone regeneration.     

Homogeneous Li+ Flux Distribution Enables Highly Stable and Temperature-Tolerant Lithium Anode

3D carbon hosts can enable low-stress Li metal anodes (LMAs) with improved structural and interfacial stability. However, the uneven Li⁺ flux and large concentration polarization, resulting from intrinsically poor Li affinity and limited porosity of carbon scaffolds, make the precise control of Li plating/stripping still one the key challenges facing advanced LMAs. Here it is demonstrated that a lightweight carbon scaffold, featuring parallel-aligned porous fibers, can work well for homogeneous Li⁺ flux distribution and reduced concentration gradient to form a stable solid electrolyte interphase, and then synergistically guide smooth Li nucleation/growth even at low temperatures. As a result, the obtained LMAs delivers a high areal capacity up to 15 mAh cm⁻², ultralong lifespan (4800 cycles at 4 mA cm⁻²) with very low voltage hysteresis of ≈21 mV, a high practically available specific capacity of 863.9 mAh g⁻¹ after 1000 cycles, and a long-term stable behavior at low-temperature operation. As coupling with the commercial LiNi_1/3Co_1/3Mn_1/3O₂ cathodes and common carbonate-based electrolyte, the corresponding practical cells also possess an ultralong lifespan and outstanding low-temperature functionality. This study not only presents an advanced carbon host candidate but also sheds new light on crucial design principles of carbon scaffolds for practically feasible rechargeable metal batteries.