Release Of Bioactive Ions Research Articles

OBTAINING AND TESTING OF MG-CA-SR BIODEGRADABLE MATERIALS USED IN MEDICINE

Biodegradable magnesium (Mg), calcium (Ca), and strontium (Sr) alloys have garnered significant interest in regenerative medicine due to their unique mechanical properties, biocompatibility, and controlled degradation combination. These materials are particularly promising for temporary implants, such as orthopedic screws, plates, and cardiovascular stents, as they eliminate the need for secondary surgical removal and provide osteogenic benefits through the release of bioactive ions. Despite their potential, the clinical implementation of Mg-Ca-Sr alloys faces several challenges, including precise control of degradation rates to match tissue healing, optimization of biocompatibility to prevent inflammatory responses, and addressing the complexities of industrial production for consistent quality and performance. Future research directions focus on employing advanced technologies like nano-engineering and 3D printing to tailor the properties of these alloys for specific applications. Long-term in vivo studies are critical for understanding their behavior in biological environments while combining these alloys with ceramics or polymers could create hybrid materials with enhanced mechanical strength and degradation control. Additionally, artificial intelligence offers opportunities to optimize material design and predict clinical outcomes. Mg-Ca-Sr alloys are promising to transform the landscape of biodegradable implants, address current limitations, and improve patient outcomes through innovative materials and fabrication techniques.

Demonstrating the potential of bioactive glass-infused electrospun PVB fibrous patches in atopic dermatitis moisturizing therapy

Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disorder characterized by pruritic and eczematous lesions. Current treatment modalities often focus on symptomatic relief through topical moisturizers to restore impaired skin barrier function. Bioactive glasses, such as 45S5 and 59S compositions, have gained attention for their potential therapeutic applications in dermatological conditions due to their biocompatibility, bioactivity, and ability to promote wound healing. In this study, we explore the feasibility and efficacy of utilizing electrospun polyvinyl butyral (PVB) fibrous patches infused with bioactive glass particles as a novel approach for moisturizing therapy in AD. The electrospun PVB fibrous patches were fabricated through a simple and scalable electrospinning technique, incorporating bioactive glass particles. Physicochemical properties, including morphology, mechanical strength, and bioactive properties, were characterized using scanning electron microscopy (SEM), tensile testing, and in- vitro bioactivity. Additionally, the protein absorption kinetics of the fibrous patches were evaluated. Furthermore, in-vitro hemocompatibility, cell viability studies and live/dead assay were conducted to assess the biocompatibility of the bioactive glass-infused PVB fibrous patches. Our findings demonstrate that the incorporation of bioactive glass particles into electrospun PVB fibrous patches confers enhanced mechanical properties and sustained release of bioactive ions, providing a promising platform for prolonged moisturizing therapy.

A poly (lactic-co-glycolic acid) self-pumping Janus dressing with bidirectional biofluid transport for diabetic wound healing via anti-bacteria and pro-angiogenesis

Diabetic wound healing poses a substantial challenge owing to bacterial infections, insufficient angiogenesis, and excessive exudates. Currently, most of the clinical dressings used for diabetic wounds are still conventional dressings such as gauze. In this study, a three-layer Janus dressing was developed via continuous electrostatic spinning. The top-layer was composed of polylactic acid-glycolic acid and hydroxyapatite doped with silver ions and silicate. The hydrophobic top-layer prevented the adhesion of foreign bacteria. The mid-layer was composed of polyethylene glycol, polylactic acid-glycolic acid and hydroxyapatite doped with silver ions and silicate facilitated exudate absorption and bioactive ion release. The modified sub-layer containing polylactic acid-glycolic acid, hydroxyapatite doped with silver ions and silicate and sodium alginate microspheres enabled both the transport of wound exudate from the wound bed to dressing and the backflow of bioactive silver ions and silicate to the wound bed, thereby reducing infection and stimulating angiogenesis. Through in vivo and in vivo experiments, the Janus dressing showed to have antimicrobial, angiogenic, and exudate-control properties that accelerate healing in diabetic wounds. As a novel dressing, the multifunctional, self-pumping Janus wound dressing with bi-directional biofluidic transport offers a new approach to diabetic wound healing.

On-demand engineered double-network gelatin/silicate composited hydrogels with enhanced wet adhesion and stable release of bioactive ion for promoting wound healing

Silicate bioceramics have demonstrated great potential in hydrogel dressings for wound healing due to their special origins of promoting endothelial cell angiogenesis and inhibiting apoptosis of cardiomyocyte. However, there are still some deficiencies, such as insufficient biological activity, instability of silicate ion release, and lower wet adhesion on wounds with tissue exudate, limiting their further clinical applications. Herein, inspired by mussels, a multifunctional double-network hydrogel (FS/PAM-Gel-PDA) wound dressing composited gelatin with silicate ceramic powder with satisfactory wet adhesion, stable release of bioactive ions, hemostasis, and the ability of promoting vascular regeneration was engineered through specifically grafting dopamine to gelatin and introducing ferrous silicate ceramic powder into the hydrogel. The comprehensive experimental results substantiate that the FS/PAM-Gel-PDA has wet-adhesion strength of up to 21.78 kPa, and remains stably adherent to porcine myocardial tissues intuitively after bending, twisting, soaking in water, and stretching. The test results of ion release behavior in vitro show that the oxidation and agglomeration of ferrous silicate ceramic powder can be effectively inhibited by using dopamine to form an antioxidant layer on the surface of ceramic powder, and thus, the stable release of Fe2+ and SiO44− effective ions can be realized. The animal experiment exhibits that FS/PAM-Gel-PDA can achieve rapid hemostasis in the lethal liver defect model. Meanwhile, the FS/PAM-Gel-PDA reveals the remarkable ability to promote wound healing in a full-thickness skin injury model, which can obviously accelerate skin re-epithelialization. To sum up, the FS/PAM-Gel-PDA has excellent wet adhesion and stable release of active ions to accelerate angiogenesis, which shows great potential in promoting wound healing.Graphical

3D Printed Pedicle Screws with Microarc Oxidation Ceramic Interfaces Enhance Osteointegration and Orthopedic Fixation Feasibility.

Effective osteointegration is of great importance for pedicle screws in spinal fusion surgeries. However, the lack of osteoinductive activity of current screws diminishes their feasibility for osteointegration and fixation, making screw loosening a common complication worldwide. In this study, Ti-6Al-4V pedicle screws with full through-hole design were fabricated via selective laser melting (SLM) 3D printing and then deposited with porous oxide coatings by microarc oxidation (MAO). The porous surface morphology of the oxide coating and the release of bioactive ions could effectively support cell adhesion, migration, vascularization, and osteogenesis in vitro. Furthermore, an in vivo goat model demonstrated the efficacy of modified screws in improving bone maturation and osseointegration, thus providing a promising method for feasible orthopedic internal fixation.

Three‐dimensional bioprinting biphasic multicellular living scaffold facilitates osteochondral defect regeneration

AbstractDue to tissue lineage variances and the anisotropic physiological characteristics, regenerating complex osteochondral tissues (cartilage and subchondral bone) remains a great challenge, which is primarily due to the distinct requirements for cartilage and subchondral bone regeneration. For cartilage regeneration, a significant amount of newly generated chondrocytes is required while maintaining their phenotype. Conversely, bone regeneration necessitates inducing stem cells to differentiate into osteoblasts. Additionally, the construction of the osteochondral interface is crucial. In this study, we fabricated a biphasic multicellular bioprinted scaffold mimicking natural osteochondral tissue employing three‐dimensional (3D) bioprinting technology. Briefly, gelatin‐methacryloyl (GelMA) loaded with articular chondrocytes and bone marrow mesenchymal stem cells (ACs/BMSCs), serving as the cartilage layer, preserved the phenotype of ACs and promoted the differentiation of BMSCs into chondrocytes through the interaction between ACs and BMSCs, thereby facilitating cartilage regeneration. GelMA/strontium‐substituted xonotlite (Sr‐CSH) loaded with BMSCs, serving as the subchondral bone layer, regulated the differentiation of BMSCs into osteoblasts and enhanced the secretion of cartilage matrix by ACs in the cartilage layer through the slow release of bioactive ions from Sr‐CSH. Additionally, GelMA, serving as the matrix material, contributed to the reconstruction of the osteochondral interface. Ultimately, this biphasic multicellular bioprinted scaffold demonstrated satisfactory simultaneous regeneration of osteochondral defects. In this study, a promising strategy for the application of 3D bioprinting technology in complex tissue regeneration was proposed.

Selective ion doping core-shell bioceramic fiber-derived granules readily tuning biodegradation and initiating osteoporotic bone defect repair

Osteoporotic bone defect repair is one of the challenges in orthopedics because there are no preferable biomaterials to readily initiate new bone regeneration in critical-size pathological bone damage. Our previous studies revealed that core–shell Ca-phosphate/silicate microspheres can tune time-evolving biodegradation, which is beneficial for modulating bone repair. Herein, we expanded this strategy to develop core–shell-type 5 % Sr- and 8 % Zn-doped wollastonite fiber-derived granules with different porosities (0 %, 10 %, 20 %) in the shell layer. Physicochemical analyses indicated that granules with higher porosity in the shell layer exhibited more appreciable Sr and Zn ion release and biodissolution in vitro. Osteoporotic femoral bony defects in rabbits were used to verify the osteogenic efficacy of the core–shell granules. The granules with 10 % porosity could initiate more osteogenesis within 6 weeks, and the new bone tissue could grow into the defect region, while the new bone tissue only migrated into the periphery pores under the other granule conditions. Histological evaluation also revealed appreciable new bone ingrowth in the granules with 10 % porosity, whereas the other implant groups had limited new bone tissue. These findings demonstrate that bone repair initiation can be enhanced by finely designed local porosity in specific components of core–shell bioceramic fiber-tailoring granules to control bioactive ion release and osteo-stimulation in vivo; moreover, such bioceramic fabrication is promising for developing osteo-stimulative implants to resolve clinically challenging bone defect repair.

Biological and Mechanical Performance of Dual-Setting Brushite-Silica Gel Cements.

Bone defects resulting from trauma, diseases, or surgical procedures pose significant challenges in the field of oral and maxillofacial surgery. The development of effective bone substitute materials that promote bone healing and regeneration is crucial for successful clinical outcomes. Calcium phosphate cements (CPCs) have emerged as promising candidates for bone replacement due to their biocompatibility, bioactivity, and ability to integrate with host tissues. However, there is a continuous demand for further improvements in the mechanical properties, biodegradability, and bioactivity of these materials. Dual setting of cements is one way to improve the performance of CPCs. Therefore, silicate matrices can be incorporated in these cements. Silicate-based materials have shown great potential in various biomedical applications, including tissue engineering and drug delivery systems. In the context of bone regeneration, silicate matrices offer unique advantages such as improved mechanical stability, controlled release of bioactive ions, and enhanced cellular responses. Comprehensive assessments of both the material properties and biological responses of our samples were conducted. Cytocompatibility was assessed through in vitro testing using osteoblastic (MG-63) and osteoclastic (RAW 264.7) cell lines. Cell activity on the surfaces was quantified, and scanning electron microscopy (SEM) was employed to capture images of the RAW cells. In our study, incorporation of tetraethyl orthosilicate (TEOS) in dual-curing cements significantly enhanced physical properties, attributed to increased crosslinking density and reduced pore size. Higher alkoxysilyl group concentration improved biocompatibility by facilitating greater crosslinking. Additionally, our findings suggest citrate's potential as an alternative retarder due to its positive interaction with the silicate matrix, offering insights for future dental material research. This paper aims to provide an overview of the importance of silicate matrices as modifiers for calcium phosphate cements, focusing on their impact on the mechanical properties, setting behaviour, and biocompatibility of the resulting composites.

Biomimetically ordered ultralong hydroxyapatite nanowires-based hierarchical hydrogel scaffold with osteoimmunomodulatory and osteogenesis abilities for augmenting bone regeneration

Artificial construction of tissue engineering implants with bone-mimicking structure and osteogenic function is of great significance for bone regeneration, but it remains a formidable challenge. Herein, inspired by natural bone, a biomimetically hierarchical hydrogel scaffold with highly ordered arrangement and multi-layered concentric circular structure is constructed by a convenient free-injection method for osteoimmunomodulation and bone defect regeneration. Ultralong hydroxyapatite nanowires act as skeleton unit to assemble into the hierarchically ordered nanowire bundles and further hybridization with hyaluronic acid methacrylate and loading with layered double hydroxide nanosheets to form the stable biomimetic scaffold. The biomimetic scaffold exhibits anisotropic structure, high water content and porosity, mechanical robustness, and sustained release of bioactive ions. In particular, the excellent biocompatibility together with ordered topography and biochemical cue can guide recruitment and directional migration of stem cells, and effectively promote osteogenic differentiation and vascularization in vitro. Moreover, the biomimetic scaffold induces M2 phenotype polarization of macrophages, thus creating a favorable osteoimmune environment. The in vivo study proves that the biomimetic scaffold can attenuate inflammation, promote vascularized ossification, and further accelerate new bone formation. This study provides an innovative strategy to construct multifunctional anisotropic biomaterials for bone tissue engineering.

Single-Atom Cu Nanozyme-Loaded Bone Scaffolds for Ferroptosis-Synergized Mild Photothermal Therapy in Osteosarcoma Treatment.

The rapid multiplication of residual tumor cells and poor reconstruction quality of new bone are considered the major challenges in the postoperative treatment of osteosarcoma. It is a promising candidate for composite bone scaffold which combines photothermal therapy (PTT) and bone regeneration induction for the local treatment of osteosarcoma. However, it is inevitable to damage the normal tissues around the tumor due to the hyperthermia of PTT, while mild heat therapy shows a limited effect on antitumor treatment as the damage can be easily repaired by stress-induced heat shock proteins (HSP). This study reports a new type of single-atom Cu nanozyme-loaded bone scaffolds, which exhibit exceptional photothermal conversion properties as well as peroxidase and glutathione oxidase mimicking activities in vitro experiments. This leads to lipid peroxidation (LPO) and reactive oxygen species (ROS) upregulation, ultimately causing ferroptosis. The accumulation of LPO and ROS also contributes to HSP70 inactivation, maximizing PTT efficiency against tumors at an appropriate therapeutic temperature and minimizing the damage to surrounding normal tissues. Further, the bone scaffold promotes bone regeneration via a continuous release of bioactive ions (Ca2+, P5+, Si4+, and Cu2+). The results of in vivo experiments reveal that scaffolds inhibit tumor growth and promote bone repair.

Blow-Spun Si3N4-Incorporated Nanofibrous Dressing with Antibacterial, Anti-Inflammatory, and Angiogenic Activities for Chronic Wound Treatment

The effective and safe healing of chronic wounds, such as diabetic ulcers, presents a significant clinical challenge due to the adverse microenvironment in the wound that hinders essential processes of wound healing, including angiogenesis, inflammation resolution, and bacterial control. Therefore, there is an urgent demand for the development of safe and cost-effective multifunctional therapeutic dressings. Silicon nitride, with its distinctive antibacterial properties and bioactivities, shows great potential as a promising candidate for the treatment of chronic wounds. In this study, a silicon nitride-incorporated collagen/chitosan nanofibrous dressing (CCS) were successfully fabricated using the solution blow spinning technique (SBS). SBS offers compelling advantages in fabricating uniform nanofibers, resulting in a three-dimensional fluffy nanofibrous scaffold that creates an optimal wound healing environment. This blow-spun nanofibrous dressing exhibits excellent hygroscopicity and breathability, enabling effective absorption of wound exudate. Importantly, the incorporated silicon nitride within the fibers triggers surface chemical reactions in the aqueous environment, leading to the release of bioactive ions that modulate the wound microenvironment. Here, the CCS demonstrated exceptional capabilities in absorbing wound exudate, facilitating water vapor transmission, and displaying remarkable antibacterial properties in vitro and in a rat infected wound model (up to 99.7%, 4.5 × 107 CFU/cm2 for Staphylococcus aureus). Furthermore, the CCS exhibited an enhanced wound closure rate, angiogenesis, and anti-inflammatory effects in a rat diabetic wound model, compared to the control group without silicon nitride incorporation.Graphical abstract

Cuprorivaite/hardystonite/alginate composite hydrogel with thermionic effect for the treatment of peri-implant lesion.

Peri-implant lesion is a grave condition afflicting numerous indi-viduals with dental implants. It results from persistent periodontal bacteria accumulation causing inflammation around the implant site, which can primarily lead to implant loosening and ultimately the implant loss. Early-stage peri-implant lesions exhibit symptoms akin to gum disease, including swelling, redness and bleeding of the gums surrounding the implant. These signs indicate infection and inflammation of the peri-implant tissues, which may result in bone loss and implant failure. To address this problem, a thermionic strategy was applied by designing a cuprorivaite-hardystonite bioceramic/alginate composite hydrogel with photothermal and Cu/Zn/Si multiple ions releasing property. This innovative approach creates a thermionic effect by the release of bioactive ions (Cu2+ and Zn2+ and ) from the composite hydrogel and the mild heat environment though the photothermal effect of the composite hydrogel induced by near-infrared light irradiation. The most distinctive advantage of this thermionic effect is to substantially eliminate periodontal pathogenic bacteria and inhibit inflammation, while simultaneously enhance peri-implant osseointegration. This unique attribute renders the use of this composite hydrogel highly effective in significantly improving the survival rate of implants after intervention in peri-implant lesions, which is a clinical challenge in periodontics. This study reveals application potential of a new biomaterial-based approach for peri-implant lesion, as it not only eliminates the infection and inflammation, but also enhances the osteointegration of the dental implant, which provides theoretical insights and practical guidance to prevent and manage early-stage peri-implant lesion using bioactive functional materials.

Nano-laponite encapsulated coaxial fiber scaffold promotes endochondral osteogenesis.

Osteoinductive supplements without side effects stand out from the growth factors and drugs widely used in bone tissue engineering. Lithium magnesium sodium silicate hydrate (laponite) nanoflake is a promising bioactive component for bone regeneration, attributed to its inherent biosafety and effective osteoinductivity. Up to now, the in vivo osteogenic potential and mechanisms of laponite-encapsulated fibrous membranes remain largely unexplored. This study presents a unique method for homogeneously integrating high concentrations of laponite RDS into a polycaprolactone (PCL) matrix by dispersing laponite RDS sol into the polymer solution. Subsequently, a core-shell fibrous membrane (10RP-PG), embedding laponite-loaded PCL in its core, was crafted using coaxial electrospinning. The PCL core's slow degradation and the shell's gradient degradation enabled the sustained release of bioactive ions (Si and Mg) from laponite. In vivo studies on a critical-sized calvarial bone defect model demonstrated that the 10RP-PG membrane markedly enhanced bone formation and remodeling by accelerating the process of endochondral ossification. Further transcriptome analysis suggested that osteogenesis in the 10RP-PG membrane is driven by Mg and Si from endocytosed laponite, activating pathways related to ossification and endochondral ossification, including Hippo, Wnt and Notch. The fabricated nanocomposite fibrous membranes hold great promise in the fields of critical-sized bone defect repair.

Dual-core-component multiphasic bioceramic granules with selective-area porous structures facilitating bone tissue regeneration and repair.

Ca-phosphate/-silicate ceramic granules have been widely studied because their biodegradable fillers can enhance bone defect repair accompanied with bioactive ion release and material degradation; however, it is a challenge to endow bioceramic composites with time-dependent ion release and highly efficient osteogenesis in vivo. Herein, we prepared dual-core-type bioceramic granules with varying chemical compositions beneficial for controlling ion release and stimulating osteogenic capability. Core-shell-structured bioceramic granules (P8-Sr4@Zn3, P8-Sr4@TCP, and P8-Sr4@HAR) composed of 8% P- and 4% Sr-substituting wollastonite (P8, Sr4) dual core components and different shell components, such as 3% Zn-substituting wollastonite (Zn3), β-tricalcium phosphate (β-TCP), and hardystonite (HAR), were prepared by cutting extruded core-shell fibers through dual-core ternary nozzles, followed by high-temperature sintering post-treatment. The experimental results showed that nonstoichiometric wollastonite core components contributed to more biologically active ion release in Tris buffer in vitro, and the sparingly dissolvable shell component readily maintained the granule morphology in vivo; thus, such bioceramic implants can adjust new bone growth and material degradation over time. In particular, bioceramic granules encapsulated by the TCP shell exhibited the most appreciable osteogenic capacity and expected biodegradation, which was mostly favorable for bone repair in critical bone defects. It is reasonable to consider that this new multiphasic bioceramic granule design is versatile for developing next-generation implants for various bone damage repairs.

Bioactive Ion-Based Switchable Supercapacitors

Switchable supercapacitors enable a reversible electrically driven uptake and release of bioactive ions by polarizing nanoporous carbon electrodes. In this work we demonstrate the first example of a bioactive ion-based switchable supercapacitor. Based on choline chloride and nanoporous carbons with defined porosity we unravel the mechanism of physisorption vs. electrosorption by nuclear magnetic resonance, Raman, and impedance spectroscopy. Weak physisorption leads to pronounced electrically driven electrolyte depletion enabling the release and capture of electrolyte ions in highly controllable and reversible manner. A new 4-terminal device structure is proposed, with a main capacitor and a smaller inserted detective capacitor for monitoring bioactive ions electrosorption in situ. Controlling the ion concentration in a printed switchable supercapacitor based on bioactive ions realizes switching down to 8.3% residual capacity.The exploration of electrically driven adsorption mechanisms in printable microdevices will open an avenue of manipulating bioactive ions for the further application of drug delivery, neuromodulation, or neuromorphic devices. Figure 1

Alendronate-decorated strontium-containing bioactive glass nanoparticles with dual osteogenic and anti-osteoclastic effects for osteoporosis

Bioactive glass (BG) has emerged as a promising material for bone regeneration. In this study, strontium-doped bioactive glass nanoparticles loaded with alendronate (A-SrBG) were fabricated and characterized to evaluate their potential for bone regeneration in osteoporosis. A-SrBG nanoparticles have excellent bioactivity, inducing apatite mineralization and achieving sustained release of bioactive ions in vitro. Moreover, A-SrBG nanoparticles could promote the differentiation of osteoblasts while inhibiting the differentiation of osteoclasts by preventing RANKL-induced activation of the NF-κB and mevalonate pathways. A-SrBG nanoparticles could be phagocytosed into the cells and present in the cytoplasm, which could enhance the efficiency of ALN. When implanted in vivo, A-SrBG discs promoted the regeneration of new bone. The results demonstrated that the ability of A-SrBG to dually regulate both osteogenesis and osteoclastogenesis makes it a promising candidate for the reconstruction of bone defects in osteoporosis.

3D-Printed Composite Bioceramic Scaffolds for Bone and Cartilage Integrated Regeneration.

Osteoarthritis may result in both cartilage and subchondral bone damage. It is a significant challenge to simultaneously repair cartilage due to the distinct biological properties between cartilage and bone. Here, strontium copper tetrasilicate/β-tricalcium phosphate (Wesselsite[SrCuSi4O10]/Ca3(PO4)2, WES-TCP) composite scaffolds with different WES contents (1, 2, and 4 wt %) were fabricated via a three-dimensional (3D) printing method for the osteochondral regeneration. The physicochemical properties and biological activities of the scaffolds were systematically investigated. 2WES-TCP (WES-TCP with 2 wt % WES) composite scaffolds not only improved the compressive strength but also enhanced the proliferation of both rabbit bone mesenchymal stem cells (rBMSCs) and chondrocytes, as well as their differentiation. The in vivo study further confirmed that WES-TCP scaffolds significantly promoted the regeneration of both bone and cartilage tissue in rabbit osteochondral defects compared with pure TCP scaffolds owing to the sustained and controlled release of bioactive ions (Si, Cu, and Sr) from bioactive scaffolds. These results show that 3D-printed WES-TCP scaffolds with bilineage bioactivities take full advantage of the bifunctional properties of bioceramics to reconstruct the complex osteochondral interface, which broadens the approach to engineering therapeutic platforms for biomedical applications.

Copper Ion-Modified Germanium Phosphorus Nanosheets Integrated with an Electroactive and Biodegradable Hydrogel for Neuro-Vascularized Bone Regeneration.

Severe bone defects accompanied by vascular and peripheral nerve injuries represent a huge orthopedic challenge and are often accompanied by the risk of infection. Thus, biomaterials with antibacterial and neurovascular regeneration properties are highly desirable. Here, a newly designed biohybrid biodegradable hydrogel (GelMA) containing copper ion-modified germanium-phosphorus (GeP) nanosheets, which act as neuro-vascular regeneration and antibacterial agents, is designed. The copper ion modification process serves to improve the stability of the GeP nanosheets and offers a platform for the sustained release of bioactive ions. Study findings show that GelMA/GeP@Cu has effective antibacterial properties. The integrated hydrogel can significantly boost the osteogenic differentiation of bone marrow mesenchymal stem cells, facilitate angiogenesis in human umbilical vein endothelial cells, and up-regulate neural differentiation-related proteins in neural stem cells in vitro. In vivo, in the rat calvarial bone defect mode, the GelMA/GeP@Cu hydrogel is found to enhance angiogenesis and neurogenesis, eventually contributing to bone regeneration. These findings indicate that in the field of bone tissue engineering, GelMA/GeP@Cu can serve as a valuable biomaterial for neuro-vascularized bone regeneration and infection prevention.

Mg‐CS/HA Microscaffolds Display Excellent Biodegradability and Controlled Release of Si and Mg Bioactive Ions to Synergistically Promote Vascularized Bone Regeneration

AbstractFor bone defect repair, it is critical to utilize biomaterials with pro‐angiogenic properties to enhance osteogenesis. Hydroxyapatite (HA)‐based materials widely used in clinical applications have shown much potential for bone repair. However, their predominant calcium phosphate (CaP) composition and poor biodegradability limit their angiogenic potential and hence osteogenic efficiency of HA‐based materials. Here, a magnesium ion‐doped calcium silicate/HA composite microscaffold (Mg‐CS/HA) is fabricated to enhance angiogenesis and osteogenic efficiency for bone repair. Incorporation of CS improved the biodegradability of the Mg‐CS/HA microscaffold, which could simultaneously release Si and Mg bioactive ions during the early stage of implantation, synergistically enhancing angiogenesis and osteogenic efficiency. In co‐culture systems, the synergistic effects of Si and Mg ions promote the “osteogenesis‐angiogenesis coupling effect.” In vivo, the Mg‐CS/HA microscaffold could significantly promote reconstruction of the vascular network and bone regeneration. This study thus provides a new strategy for coordinated release of bioactive ions to achieve synergistic effects on vascularized bone regeneration by HA‐based bone implant materials.

Core-shell-typed selective-area ion doping wollastonite bioceramic fibers enhancing bone regeneration and repair in situ

Silicate-based bioceramics are being received great attention because of its potential osteostimulative properties in facilitating bone regeneration. Meanwhile, foreign ion doping in bioceramics is a versatile strategy for regulating the biological performances. Herein we developed the new core-shell-typed wollastonite bioceramic fibers (Zn8@Mg10) with 8% Zn and 10% Mg selective-area doping. It was found that the fibrous diameter of Zn-doped core layer could be finely tuned by the extrusion force through the coaxially aligned bi-nozzle system and thus the ultralong bioceramic fibers with different core-shell thickness ratios (2:4, 3:3; 4:2) could be fabricated after sintering treatment. The Zn8@Mg10 fibers exhibited tailorable Zn and Mg ion release and more controllable bio-dissolution in vitro in comparison with the mechanically mixed Zn8/Mg10 fibers. The osteogenic efficacy of core-shell fibers was validated in femoral bony defect in rabbits. The fibers with equal core/shell thickness (3:3) showed more appreciable osteogenic capability after 8 weeks and the new bone tissue could grow into the entire defected region, while the Zn8/Mg10 group only presented new bone at the boundary. Histological examination also indicated more appreciable bone formation in the core-shell fiber groups, whereas less new bone ingrowth was observed in the Zn8/Mg10 group. These findings indicate that bone repair can be enhanced by component distribution design to control bioactive ion release and osteostimulation in vivo. It is demonstrated that selective-area ions doping bioceramics can be translated to a core-shell-structuring strategy through layer thickness adjustment and fiber fabrication with strong clinical translation.