A Surface-Mediated Biomimetic Porous Polyether-Ether-Ketone Scaffold for Regulating Immunity and Promoting Osteogenesis.

The repair of critical-sized bone defects remains a major challenge for clinical orthopedic surgery. Here, we develop a surface biofunctionalized three-dimensional (3D) porous polyether-ether-ketone (PEEK) scaffold that can simultaneously promote osteogenesis and regulate macrophage polarization. The scaffold is created using polydopamine (PDA)-assisted immobilization of silk fibroin (SF) and the electrostatic self-assembly of nanocrystalline hydroxyapatite (nano-HA) on a 3D-printed porous PEEK scaffold. The SF/nano-HA functionalized surface provides a bone-like microenvironment for osteoblastic cells' adhesion, proliferation, mineralization and osteogenic differentiation. Moreover, the biofunctionalized surface can effectively drive macrophages polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Integrin ß1-specific cell-matrix binding and the activation of Ca2+ receptor-mediated signaling pathway play critical roles in the regulation of macrophage polarization. Compared with the as-printed scaffold, the SF/nano-HA functionalized porous PEEK scaffold induces minimal inflammatory response, enhanced angiogenesis, and substantial new bone formation, resulting in improved osseointegration in vivo. This study not only develops a promising candidate for bone repair but also demonstrates a facile surface biofunctionalization strategy for orthopedic implants to improve osseointegration by stimulating osteogenesis and regulating immunity.

Peek@ZIF-8(CEL) as a Novel Bone Implant for Large Defect Repair and Enhanced Bone Healing via a Long-Term Stable Bioactive Releaser.

The repair of large bone defects poses a significant challenge in orthopedics. Polyetheretherketone (PEEK) is a promising bone substitute, while it suffers a lack of bioactivity. Although several studies have been performed to further improve the bioactivities of PEEK by various surface modifications, PEEK offering long-term, multifaceted biofunctionalities remains still desired. In this study, we introduced metal-organic frameworks (MOFs), specifically ZIF-8 loaded with celecoxib (ZIF-8(CEL)), onto the PEEK surface through dopamine adhesion. The resulting PEEK@ZIF-8(CEL) aims to achieve long-term stable release of Zn ions and CEL for enhanced bone integration. Material characterization and biological experiments confirmed the successful integration of ZIF-8(CEL) onto PEEK and its positive biomedical effects, including creating a positive bone immunological environment and promoting bone growth. This study demonstrates the potential of PEEK@ZIF-8(CEL) as a novel repair material for large bone defects, offering a promising alternative in orthopedic applications.

Harnessing chemical functionality of xylan hemicellulose towards carbohydrate polymer-based pH/magnetic dual-responsive nanocomposite hydrogel for drug delivery.

This study reports a pH/magnetic dual-responsive hemicellulose-based nanocomposite hydrogel with nearly 100 % carbohydrate polymer-based and biodegradable polymer compositions for drug delivery. We synthesized pure Fe3O4 magnetic nanoparticles (Fe3O4 MNPs) using a co-precipitation method, then engineering xylan hemicellulose (XH), acrylic acid, poly(ethylene glycol) diacrylate, and Fe3O4 to synthesize the pH/magnetic dual-responsive hydrogel (Fe3O4@XH-Gel), through graft polymerization on XH with in-situ doping Fe3O4 MNPs initiated by the ammonium persulfate/tetramethylethylenediamine redox system. Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (1H NMR), X-ray diffractometry (XRD), scanning electron microscopy and energy dispersive spectrometer (SEM-EDS), high-resolution transmission electron microscopy (HRTEM), Brunauer-Emmett-Teller (BET), swelling gravimetric analysis, vibrating sample magnetometer (VSM) were employed to analyze the hydrogel's chemical structures, morphologies, pH-responsive behaviors, and magnetic responsiveness characteristics, mechanical and rheological properties, as well as cytotoxicity and biodegradability. The results indicate that the Fe3O4@XH-Gel exhibited excellent dual responsiveness to pH and magnetism. Furthermore, an emphasis was placed on the in-depth analysis of the pH response mechanism. Finally, we utilized this cutting-edge hydrogel to investigate the controlled-release behavior of two model drugs, Acetylsalicylic acid and Theophylline. The hydrogel demonstrated exceptional controlled release attributes, positioning it as a potential carrier for targeted drug delivery, particularly to the gastrointestinal conditions.

A multifunctional biogenic films and coatings from synergistic aqueous dispersion of wood-derived suberin and cellulose nanofibers.

Here, biogenic and multifunctional active food coatings and packaging with UV shielding and antimicrobial properties were structured from the aqueous dispersion of an industrial byproduct, suberin, which was stabilized with amphiphilic cellulose nanofibers (CNF). The dual-functioning CNF, synthesized in a deep eutectic solvent, functioned as an efficient suberin dispersant and reinforcing agent in the packaging design. The nanofibrillar percolation network of CNF provided a steric hindrance against the coalescence of the suberin particles. The low CNF dosage of 0.5 wt% resulted in dispersion with optimal viscosity (208.70 Pa.s), enhanced stability (instability index of <0.001), and reduced particle size (9.37 ± 2.43 µm). The dispersion of suberin and CNF was further converted into self-standing films with superior UV-blocking capability, good thermal stability, improved hydrophobicity (increase in water contact angle from 61° ± 0.15 to 83° ± 5.11), and antimicrobial properties against gram-negative bacteria. Finally, the synergistic bicomponent dispersions were demonstrated as fruit coatings for bananas and packaging for strawberries to promote their self-life. The coatings and packaging considerably mitigated fruit deterioration and improved their freshness by preventing moisture loss and microbial attack. This sustainable approach is expected to pave the way toward advanced, biogenic, and active food packaging based on widely available bioresources.

Aqueous Processable One-Dimensional Polypyrrole Nanostructured by Lignocellulose Nanofibril: A Conductive Interfacing Biomaterial.

One-dimensional (1D) nanomaterials of conductive polypyrrole (PPy) are competitive biomaterials for constructing bioelectronics to interface with biological systems. Synergistic synthesis using lignocellulose nanofibrils (LCNF) as a structural template in chemical oxidation of pyrrole with Fe(III) ions facilitates surface-confined polymerization of pyrrole on the nanofibril surface within a submicrometer- and micrometer-scale fibril length. It yields a core-shell nanocomposite of PPy@LCNF, wherein the surface of each individual fibril is coated with a thin nanoscale layer of PPy. A highly positive surface charge originating from protonated PPy gives this 1D nanomaterial a durable aqueous dispersity. The fibril-fibril entanglement in the PPy@LCNFs facilely supported versatile downstream processing, e.g., spray thin-coating on glass, flexible membranes with robust mechanics, or three-dimensional cryogels. A high electrical conductivity in the magnitude of several to 12 S·cm-1 was confirmed for the solid-form PPy@LCNFs. The PPy@LCNFs are electroactive and show potential cycling capacity, encompassing a large capacitance. Dynamic control of the doping/undoping process by applying an electric field combines electronic and ionic conductivity through the PPy@LCNFs. The low cytotoxicity of the material is confirmed in noncontact cell culture of human dermal fibroblasts. This study underpins the promises for this nanocomposite PPy@LCNF as a smart platform nanomaterial in constructing interfacing bioelectronics.

Surface modifications of titanium dental implants with strontium eucommia ulmoides to enhance osseointegration and suppress inflammation.

BACKGROUND: Titanium (Ti) is now widely used as implant material due to its excellent mechanical properties and superior biocompatibilities, while its inert bioactivities might lead to insufficient osseointegration, and limit its performance in dental applications. METHODS: We introduced a robust and simple approach of modifying titanium surfaces with polysaccharide complexes. Titanium samples were subjected to hydrothermal treatment to create a uniform porous structure on the surface, followed by coating with a bioinspired and self-assembly polydopamine layer. Strontium Eucommia Ulmoides Polysaccharide (EUP-Sr) complexes are then introduced to the polydopamine-coated porous titanium. Multiple morphological and physiochemical characterizations are employed for material evaluation, while cell proliferation and gene expression tests using macrophages, primary alveolar bone osteoblasts, and vascular endothelial cells are used to provide an overall insight into the functions of the product. The significances of statistical differences were analyzed using student's t-test. RESULTS: Microscopic and spectrometric characterizations confirmed that the Ti surface formed a porous structure with an adequate amount of EUP-Sr loading. The attachment was attributed to hydrogen bonding between the ubiquitous glycosidic linkage of the polysaccharide complex and the ring structure of polydopamine, yet the loaded EUP-Sr complex can be gradually released, consequently benefiting the neighboring microenvironment. Cell experiments showed no cytotoxicity of the material, and the product showed promising anti-inflammation, osseointegration, and angiogenesis properties, which were further confirmed by in vivo evaluations. CONCLUSION: We believe the EUP-Sr modified titanium implant is a promising candidate to be used in dental applications with notable osteoimmunomodulation and angiogenesis functions. And the novel technique proposed in this study would benefit the modification of metal/inorganic surfaces with polysaccharides for future research.

The development of novel multifunctional drug system 7,8-DHF@ZIF-8 and its potential application in bone defect healing.

Physical exercise has long been considered an essential regulator of bone formation. Recent studies have shown that brain-derived neurotrophic factor (BDNF) is an important cytokine released during physical exercise to promote osteogenic differentiation and facilitate the bone defect healing process. In this study, we developed a multifunctional system 7,8-DHF@ZIF-8, which combines the superior osteogenesis and angiogenesis properties of ZIF-8 and the unique capability of 7,8-DHF to mimic the function of BDNF to compensate for the routine physical exercise missed during the bone defect period. Various material characterizations were performed to confirm the successful synthesis of 7,8-DHF@ZIF-8. Drug release experiments suggested that 7,8-DHF@ZIF-8 could achieve slow diffusive release under physiological conditions within seven days. In vitro cell experiments indicated that low concentrations of ZIF-8 and 7,8-DHF@ZIF-8 could significantly promote the proliferation of MC3T3-E1 cells. Moreover, as proved by RT-QPCR analysis, incorporating 7,8-DHF into ZIF-8 could further enhance osteogenesis and angiogenesis-related gene expression. Therefore, we believe that the multifunctional drug system 7,8-DHF@ZIF-8 should have promising applications to facilitate bone defect healing.

Strontium-modified porous polyetheretherketone with the triple function of osteogenesis, angiogenesis, and anti-inflammatory for bone grafting.

Polyetheretherketone (PEEK) is a potential bone repair material because of its stable chemical and good mechanical properties. However, the biological inertness of PEEK limits its clinical application. Sr2+ has multi biological functions, including promoting bone formation and blood vessel regeneration and inhibiting inflammation. In this paper, PEEK was modified with Sr2+ with the purpose to construct PEEK bone graft material with triple functions of osteogenesis, angiogenesis, and anti-inflammatory. The results showed that Sr-modified PEEK could stably release Sr2+ for a long time in the PBS solution, and indeed could promote the proliferation and differentiation of osteoblasts, promote angiogenesis, and inhibit inflammation. Therefore, it is believed that this multifunctional PEEK with Sr2+ should show great promise for clinical applications in bone repair.

Water-soluble polysaccharides promoting production of redispersible nanocellulose.

To date, the energy-intensive production and high-water content severely limits nanocellulose applications on a large scale off-site. In this study, adding water-soluble polysaccharides (PS) to achieve an integrated process of water-redispersible nanocellulose production was well established. The addition of PS, in particular carboxymethylated-galactoglucomannan (cm-GGM), facilitates fibre fibrillation enabling homogenization at a higher solid content at 1.5 wt% compared with around 0.4 wt% for neat fibre. More importantly, the addition of cm-GGM saved 73 % energy in comparison without PS addition. Good water redispersibility of thus-prepared nanocellulose was validated in viewpoints of size distribution, morphology, viscosity and film properties as compared with neat nanocellulose. The tensile strength and optical transmittance of nanocellulose films increased to 116 MPa and 77 % compared to those without PS addition of 62 MPa and 74 %, respectively. Collectively, this study provides a new avenue for large-volume production of redispersible nanocellulose at a high solid content with less energy-consumption.

A cannabidiol-containing alginate based hydrogel as novel multifunctional wound dressing for promoting wound healing.

In addition to preventing infection and promoting angiogenesis, novel hydrogel dressings are highly expected to possess the potential to scavenge reactive oxygen species (ROS) and reduce inflammatory responses during the wound healing process. In this study, we designed and fabricated a hydrogel dressing (CBD/Alg@Zn) containing cannabidiol (CBD) based on the ion crosslinked interaction between Zn2+ ions and the alginate polymer (Alg). The as-fabricated hydrogel exhibited a suitable swelling ratio, sufficient thermal stability, and stable rheological property. In vitro biological activity experiments indicated that the hydrogel has good biocompatibility, antibacterial activity, and angiogenesis properties. Moreover, it could significantly scavenge DPPH (2,2-diphenyl-1-picrylhydrazyl) free radicals and reduce the inflammatory response. In vivo studies revealed that the CBD/Alg@Zn hydrogel significantly facilitated the wound healing process by controlling the inflammatory infiltration, promoting collagen deposition and the granulation tissue, and benefiting the formation of blood vessels. We, therefore, suggested that CBD/Alg@Zn hydrogel should be a potential candidate material for wound dressing and skin tissue engineering.

Surface Modification of Poly(ether ether ketone) by Simple Chemical Grafting of Strontium Chondroitin Sulfate to Improve its Anti-Inflammation, Angiogenesis, Osteogenic Properties.

Besides inducing osteogenic differentiation, the surface modification of poly(ether ether ketone) (PEEK) is highly expected to improve its angiogenic activity and reduce the inflammatory response in the surrounding tissue. Herein, strontium chondroitin sulfate is first attempted to be introduced into the surface of sulfonated PEEK (SPEEK-CS@Sr) based on the Schiff base reaction between PEEK and ethylenediamine (EDA) and the amidation reaction between EDA and chondroitin sulfate (CS). The surface characteristics of SPEEK-CS@Sr implant are systematically investigated, and its biological properties in vitro and in vivo are also evaluated. The results show that the surface of SPEEK-CS@Sr implant exhibits a 3D microporous structure and good hydrophilicity, and can steadily release Sr ions. Importantly, the SPEEK-CS@Sr not only displays excellent biocompatibility, but also can remarkably promote cell adhesion and spread, improve osteogenic activity and angiogenic activity, and reduce the inflammatory response compared to the original PEEK. Therefore, this study presents the surface modification of PEEK material by simple chemical grafting of strontium chondroitin sulfate to improve its angiogenesis, anti-inflammation, and osteogenic properties, and the as-fabricated SPEEK-CS@Sr has the potential to serve as a promising orthopedic implant in bone tissue engineering.

Strontium based Astragalus polysaccharides promote osteoblasts differentiation and mineralization.

Bone formation and repair represent a clinical challenge. In this work, we designed and synthesized strontium Astragalus polysaccharide (APS-Sr), a novel polysaccharide compound that should have therapeutic effects on both anti-inflammation and promoting bone formation. Using material characterization techniques, including SEM, FITR, XRD, etc., we verified the successful synthesis of this compound. Moreover, we examined the potential of this compound for promoting bone repair and inhibiting inflammatory response by cell proliferation assay, ALP and Alizarin Red staining experiments and RT-qPCR. The biological experiment results showed that APS-Sr can effectively inhibit inflammatory factors, promote osteogenic differentiation and up-regulate the bone growth factors. It is therefore believed that APS-Sr should be a promising polysaccharide compound in bone-related biomedical applications.

Dynamic Alteration of the Gut Microbiota Associated with Obesity and Intestinal Inflammation in Ovariectomy C57BL/6 Mice.

OBJECTIVE: Estrogen is a critical hormone that is mainly produced by the ovary in females. Estrogen deficiency leads to various syndromes and diseases, partly due to gut microbiota alterations. Previous studies have shown that estrogen deficiency affects the gut microbiota at 6-8 weeks after ovariectomy, but the immediate effect of estrogen deficiency on the gut microbiota remains poorly understood. METHODS: To investigate the short time and dynamic effects of decreased estrogen levels on the gut microbiota and their potential impact on estrogen deficiency-related diseases, we performed metagenomic sequencing of 260 fecal samples from 50 ovariectomy (OVX) and 15 control C57BL/6 female mice at four time points after surgery. RESULTS: We found that seven gut microbiota species, including E. coli, Parabacteroides unclassified, Lachnospiraceae bacterium 8_1_57FAA, Bacteroides uniformis, Veillonella unclassified, Bacteroides xylanisolvens, and Firmicutes bacterium M10_2, were abundant in OVX mice. The abundance of these species increased with time after OVX surgery. The relative abundance of the opportunistic pathogen E. coli and the Crohn's disease-related Veillonella spp. was significantly correlated with mouse weight gain in the OVX group. Butyrate production and the Entner-Doudoroff pathway were significantly enriched in the control mouse group, while the degradation of glutamic acid and aspartic acid was enriched in the OVX mouse group. As the time after OVX surgery increased, the bacterial species and metabolic pathways significantly changed and tended to suggest an inflammatory environment, indicating a subhealthy state of the gut microbiota in the OVX mouse group. CONCLUSIONS: Taken together, our results show that the dynamic gut microbiota profile alteration caused by estrogen deficiency is related to obesity and inflammation, which may lead to immune and metabolic disorders. This study provides new clues for the treatment of estrogen deficiency-related diseases.

Development and characterization of cannabidiol-loaded alginate copper hydrogel for repairing open bone defects in vitro.

The clinical treatment of open bone defects caused by accidental bone trauma, bone tumors, bone diseases and bone infections is challenging. In this study, we designed and fabricated a multifunctional alginate-based hydrogel that contains cannabidiol (CBD), SA@Cu/CBD hydrogel, for repairing open bone defects. The results of physicochemical characterization showed that the SA@Cu/CBD hydrogel was successfully prepared and showed a suitable swelling ratio, high thermal stability, and stable mechanical properties. In vitro evaluation of antibacterial activity indicated that more than 90% of S. aureus and E. coli were inhibited compared to the control group. The ALP activity assay showed that the ALP expression level of MC3T3-E1cells in SA@Cu/CBD hydrogel was approximately 2-fold higher than that in the control group on day 7 and 14. Additionally, compared to the control group, the level of mineralized deposits in SA@Cu/CBD hydrogel was also improved by about 2 times on day 14. The PCR results indicated the mRNA expression levels of osteogenic markers (ALP, Col1α1, OCN, and RUNX2 genes) and angiogenic markers (EGFL6 and VEGF genes) in SA@Cu/CBD hydrogel were significantly upregulated compared to that in the control group, and the mRNA expression levels of critical inflammatory cytokines (TNF-α and IL-1ß) in the SA@Cu/CBD hydrogel were significantly down-regulated compared to that in SA@Cu hydrogel. Taken together, these results demonstrated that the SA@Cu/CBD hydrogel showed significantly anti-bacterial, anti-inflammation, angiogenic and osteogenic activities in vitro studies. Thus, SA@Cu/CBD hydrogels may be a promising candidate in repairing open bone defects.

Chondroitin sulfate zinc with antibacterial properties and anti-inflammatory effects for skin wound healing.

A chondroitin sulfate zinc (CSZn) complex was prepared by an ion-exchange method. The purified product was characterized by energy-dispersive X-ray spectroscopy, high-performance chromatography, elemental analysis, Fourier transform infrared spectroscopy, inductively coupled mass spectrometry, and nuclear magnetic resonance spectroscopy. The CSZn demonstrated antibacterial activity against Escherichia coli and Staphylococcus aureus and satisfied MTT cell viability (NIH3T3 fibroblasts) at ≤50 µg/mL. RT-PCR demonstrated significant promotion by CSZn of fibroblast growth factor beta (ß-FGF), collagen III (COLIIIα1), vascular endothelial growth factor (VEGF) and reduction of cytokines IL-6, IL-1ß & TNF-alpha. An in vivo rat full-thickness wound healing model demonstrated significant wound healing of CSZn relative to controls of saline treatment, zinc chloride treatment and chondroitin treatment. CSZn has demonstrated promising antibacterial and wound healing properties making it deserving of consideration for more advanced wound healing applications.

Extracellular Calcium Ion Concentration Regulates Chondrocyte Elastic Modulus and Adhesion Behavior.

Extracellular calcium ion concentration levels increase in human osteoarthritic (OA) joints and contribute to OA pathogenesis. Given the fact that OA is a mechanical problem, the effect of the extracellular calcium level ([Ca2+]) on the mechanical behavior of primary human OA chondrocytes remains to be elucidated. Here, we measured the elastic modulus and cell-ECM adhesion forces of human primary chondrocytes with atomic force microscopy (AFM) at different extracellular calcium ion concentration ([Ca2+]) levels. With the [Ca2+] level increasing from the normal baseline level, the elastic modulus of chondrocytes showed a trend of an increase and a subsequent decrease at the level of [Ca2+], reaching 2.75 mM. The maximum increment of the elastic modulus of chondrocytes is a 37% increase at the peak point. The maximum unbinding force of cell-ECM adhesion increased by up to 72% at the peak point relative to the baseline level. qPCR and immunofluorescence also indicated that dose-dependent changes in the expression of myosin and integrin ß1 due to the elevated [Ca2+] may be responsible for the variations in cell stiffness and cell-ECM adhesion. Scratch assay showed that the chondrocyte migration ability was modulated by cell stiffness and cell-ECM adhesion: as chondrocyte's elastic modulus and cell-ECM adhesion force increased, the migration speed of chondrocytes decreased. Taken together, our results showed that [Ca2+] could regulate chondrocytes stiffness and cell-ECM adhesion, and consequently, influence cell migration, which is critical in cartilage repair.

Strontium Laminarin polysaccharide modulates osteogenesis-angiogenesis for bone regeneration.

Bone regeneration and repair has become one of the major clinical challenges worldwide and it involves multiple processes including inflammation, angiogenesis and osteogenesis. In this study, we synthesized strontium Laminarin polysaccharide (LP-Sr), a novel polysaccharide-metal complex that should have therapeutic effects on modulating osteogenesis and angiogenesis. The structure and composition of the as-fabricated LP-Sr were analyzed by EDS, XRD, FITR, 1H NMR, HPLC, etc. The results indicate that we successfully synthesized this novel polysaccharide complex. Moreover, we evaluated the biomedical potential of this complex in promoting osteogenesis and angiogenesis by cell proliferation assay, ALP staining, immunofluorescent staining of CD31 and reverse transcription polymerase chain reaction (RT-PCR). The biological experiment results show that LP-Sr can effectively promote proliferation and increase the expression of VEGF and EGFL6 in HUVECs and significantly up-regulate the expression of Col1α1 and OCN in MC3T3-E1. Besides, it is suggested that LP-Sr has positive effects on the suppression of pro-inflammatory factor IL6 in both HUVECs and MC3T3-E1. Moreover, the osteogenic and angiogenic markers, i.e. alkaline phosphatase (ALP) and CD31, exhibited high expression in LP-Sr group. Hence, we believe that LP-Sr should be a promising and novel polysaccharide complex in modulating osteogenesis-angiogenesis for bone regeneration.

Circulating MicroRNA-19b Identified From Osteoporotic Vertebral Compression Fracture Patients Increases Bone Formation.

Circulating microRNAs (miRNAs) play important roles in regulating gene expression and have been reported to be involved in various metabolic diseases, including osteoporosis. Although the transcriptional regulation of osteoblast differentiation has been well characterized, the role of circulating miRNAs in this process is poorly understood. Here we discovered that the level of circulating miR-19b was significantly lower in osteoporotic patients with vertebral compression fractures than that of healthy controls. The expression level of miR-19b was increased during osteoblastic differentiation of human mesenchymal stem cells (hMSCs) and MC3T3-E1 cells, and transfection with synthetic miR-19b could promote osteoblastic differentiation of hMSCs and MC3T3-E1 cells. PTEN (phosphatase and tensin homolog deleted from chromosome 10) was found to be directly repressed by miR-19b, with a concomitant increase in Runx2 expression and increased phosphorylation of AKT (protein kinase B, PKB). The expression level of circulating miR-19b in aged ovariectomized mice was significantly lower than in young mice. Moreover, the osteoporotic bone phenotype in aged ovariectomized mice was alleviated by the injection of chemically modified miR-19b (agomiR-19b). Taken together, our results show that circulating miR-19b plays an important role in enhancing osteoblastogenesis, possibly through regulation of the PTEN/pAKT/Runx2 pathway, and may be a useful therapeutic target in bone loss disorders, such as osteoporosis. © 2019 American Society for Bone and Mineral Research.

Multifunctional Nanoengineered Hydrogels Consisting of Black Phosphorus Nanosheets Upregulate Bone Formation.

Tissue-engineered hydrogels have received extensive attention as their mechanical properties, chemical compositions, and biological signals can be dynamically modified for mimicking extracellular matrices (ECM). Herein, the synthesis of novel double network (DN) hydrogels with tunable mechanical properties using combinatorial screening methods is reported. Furthermore, nanoengineered (NE) hydrogels are constructed by addition of ultrathin 2D black phosphorus (BP) nanosheets to the DN hydrogels with multiple functions for mimicking the ECM microenvironment to induce tissue regeneration. Notably, it is found that the BP nanosheets exhibit intrinsic properties for induced CaP crystal particle formation and therefore improve the mineralization ability of NE hydrogels. Finally, in vitro and in vivo data demonstrate that the BP nanosheets, mineralized CaP crystal nanoparticles, and excellent mechanical properties provide a favorable ECM microenvironment to mediate greater osteogenic cell differentiation and bone regeneration. Consequently, the combination of bioactive chemical materials and excellent mechanical stimuli of NE hydrogels inspire novel engineering strategies for bone-tissue regeneration.

Facile Surface Modification Method for Synergistically Enhancing the Biocompatibility and Bioactivity of Poly(ether ether ketone) That Induced Osteodifferentiation.

Poly(ether ether ketone) (PEEK) is a promising material in biomedical engineering due to its suitable mechanical properties and excellent chemical resistance and biocompatibility. However, the biological inertness of PEEK limits its applications. In this study, we developed a facile approach of immersion to generate a biocompatible and bioactive PEEK that induced osteodifferentiation. First, micropores on the surface of PEEK were introduced by concentrated sulfuric acid and subsequent water immersion, followed by the hydrothermal treatment to reduce residual sulfuric acid. Subsequently, the sulfonated PEEK surface was activated by the oxygen plasma treatment and then coated with a poly(dopamine) (PDA) layer by immersion into the dopamine solution. Finally, the tripeptide Arg-Gly-Asp (RGD) was integrated onto the PDA-coated surface of PEEK by immersion into the RGD peptide solution. The surface characteristics (physical chemistry and biological properties) and the ability to form bonelike apatite were systematically investigated by scanning electron microscopy, X-ray photoelectron spectroscopy, water contact angle analysis, the Archimedes' fluid saturation method, ellipsometry, a quartz crystal microbalance with dissipation monitoring, cell proliferation, real-time reverse transcription polymerase chain reaction analysis, alizarin red staining, immunocytochemistry staining, and simulated body fluid immersion. Collectively, the modified PEEK showed a significantly improved ability to promote cell proliferation, osteogenic differentiation, and bonelike apatite formation in vitro as compared to the PEEK control. These results demonstrate that combined facile surface modifications for PEEK enhance its bioactivity and biocompatibility, and induce osteodifferentiation. This study presents a strategy for broadening the use of PEEK in the application of orthopedic implants and could be industrially scalable in future.