Surface Biofunctionalization of Gadolinium Phosphate Nanobunches for Boosting Osteogenesis/Chondrogenesis Differentiation.

In order to achieve smart biomedical micro/nanomaterials, promote interaction with biomolecules, improve osteogenic/chondrogenic differentiation, exhibit better dispersion in bone implants and ultimately maximize functionality, we innovatively and successfully designed and synthesized polymer PBLG-modified GdPO4·H2O nanobunches by hydroxylation, silylation and glutamylation processes. The effects of different feeding ratios on the surface coating of GdPO4·H2O with Si-OH, the grafting γ-aminopropyltriethoxysilane (APS) and the in situ ring-opening polymerization reaction of poly(g-benzyl-L-glutamate) (PBLG) were investigated, and the physical and chemical properties were characterized in detail. When GdPO4·H2O@SiO2-APS:NCA = 4:1, the PBLG-g-GdPO4·H2O grafting rate was 5.93%, with good stability and dispersion in degradable polymeric materials. However, the MRI imaging signal was sequentially weakened as the modification process proceeded. Despite this, the biological effects had surprising findings. All the modifiers at appropriate concentrations were biocompatible and biologically active and the biomacromolecules of COL I and COL II in particular were expressed at least 3 times higher in GdPO4·H2O@SiO2 compared to the PLGA. This indicates that the appropriate surface modification and functionalization of gadolinium-containing micro/nanomaterials can promote interaction with cells and encourage bone regeneration by regulating biomacromolecules and can be used in the field of biomedical materials.

Enhanced in Vitro Mineralization and in Vivo Osteogenesis of Composite Scaffolds through Controlled Surface Grafting of L-Lactic Acid Oligomer on Nanohydroxyapatite.

Nanocomposite of hydroxyapatite (HA) surface grafted with L-lactic acid oligomer (LAc oligomer) (op-HA) showed improved interface compatibility, mechanical property, and biocompatibility in our previous study. In this paper, composite scaffolds of op-HA with controlled grafting different amounts of LAc oligomer (1.1, 5.2, and 9.1 wt %) were fabricated and implanted to repair rabbit radius defects. The dispersion of op-HA nanoparticles was more uniform than n-HA in chloroform and nanocomposites scaffold. Calcium and phosphorus exposure, in vitro biomineralization ability, and cell proliferation were much higher in the op-HA1.1 wt %/PLGA scaffolds than the other groups. The osteodifferentiation and bone fusion in animal tests were significantly enhanced for op-HA5.2 wt %/PLGA scaffolds. The results indicated that the grafted LAc oligomer of 5.2 or 9.1 wt %, which formed a barrier layer on the HA surface, prevented the exposure of nucleation sites. The shielded nucleation sites of op-HA particles (5.2 wt %) might be easily exposed as the grafted LAc oligomer was decomposed easily by enzyme systems in vivo. Findings from this study have revealed that grafting 1.1 wt % amount of LAc oligomer on hydroxyapatite could improve in vitro mineralization, and 5.2 wt % could promote in vivo osteogenesis capacity of composite scaffolds.

A Bioorthogonal Approach for the Preparation of a Titanium-Binding Insulin-like Growth-Factor-1 Derivative by Using Tyrosinase.

The generation of metal surfaces with biological properties, such as cell-growth-enhancing and differentiation-inducing abilities, could be potentially exciting for the development of functional materials for use in humans, including artificial dental implants and joint replacements. However, currently the immobilization of proteins on the surfaces of the metals are limited. In this study, we have used a mussel-inspired bioorthogonal approach to design a 3,4-hydroxyphenalyalanine-containing recombinant insulin-like growth-factor-1 using a combination of recombinant DNA technology and tyrosinase treatment for the surface modification of titanium. The modified growth factor prepared in this study exhibited strong binding affinity to titanium, and significantly enhanced the growth of NIH3T3 cells on the surface of titanium.

In vitro study of electroactive tetraaniline-containing thermosensitive hydrogels for cardiac tissue engineering.

Injectable hydrogels made of degradable biomaterials can function as both physical support and cell scaffold in preventing infarct expansion and promoting cardiac repair in myocardial infarction therapy. Here, we report in situ hydrogels consisting of thermosensitive PolyNIPAM-based copolymers and electroactive tetraaniline (TA). Studies showed that the addition of 2-methylene-1,3-dioxepane (MDO) provided the PolyNIPAM-based gel with biodegradability, and the introduction of tetraaniline endowed these copolymers with desirable electrical properties and antioxidant activities. The encapsulated H9c2 cells (rat cardiac myoblast) remained highly viable in the gel matrices. In vivo gel formation and histological analyses were performed in rats by subcutaneous injection and excellent biocompatibility was observed. Furthermore, the proliferation and intracellular calcium transients of H9c2 cells were also studied with (and without) electrical stimuli. Both in vitro and in vivo results demonstrated that electroactive hydrogel may be used as a promising injectable biomaterial for cardiac tissue engineering.

In vitro studies on regulation of osteogenic activities by electrical stimulus on biodegradable electroactive polyelectrolyte multilayers.

In this study, a novel electroactive tetreaniline-containing degradable polyelectrolyte multilayer film (PEM) coating [(poly(l-glutamic acid)-graft-tetreaniline/poly(l-lysine)-graft-tetreaniline)n, (PGA-g-TA/PLL-g-TA)n] was designed and fabricated by layer-by-layer (LbL) assembly method. Compared with the nongrafted PEMs, the tetreaniline-grafted PEMs showed higher roughness and stiffness in micro/nanoscale structures. The special surface characteristics and the typical electroconductive properties were more beneficial for adhesion, proliferation, and differentiation of preosteoblast MC3T3-E1 cells. Moreover, the enhanced effects were observed on the modulation of MC3T3-E1 cells that differentiated into maturing osteoblasts, when the electroactive PEMs were coupled with electrical stimulus (ES), especially in the early phase of the osteoblast differentiation. The alkaline phosphatase (ALP) activity, calcium deposition, immunofluorescence staining, and RT-qPCR were evaluated on the differentiation of preosteoblast. These data indicate that the comprehensive effects through coupling electroactive scaffolds with electrical stimulus are better to develop bioelectric strategies to control cell functions for bone regeneration.

Glucose microenvironment sensitive degradation of arginine modified calcium sulfate reinforced poly(lactide-co-glycolide) composite scaffolds.

Poly(lactide-co-glycolide) (PLGA) and calcium sulfate composites are promising biodegradable biomaterials but are still challenging to use in people with high levels of blood glucose or diabetes. To date, the influence of glucose on their degradation has not yet been elucidated and thus calls for more research attention. Herein, a novel calcium sulfate whisker with L-arginine was used to effectively tune its crystal morphology and was employed as a reinforced phase to construct the PLGA-based composite scaffolds (ArgCSH/PLGA) with a sleeve porous structure. ArgCSH/PLGA showed excellent elastic modulus and strength in the compression and bending models. Moreover, an in vitro immersion test showed that ArgCSH/PLGA possessed degradation and redeposition behaviors sensitive to glucose concentration, and the adsorbed Arg played a crucial role in the degradation process. The subsequent cell functional evaluation showed that ArgCSH could effectively protect cells from damage caused by AGEs and promote osteogenic differentiation. The corresponding degradation products of ArgCSH/PLGA displayed the ability to regulate osteoblast bone differentiation and accelerate matrix mineralization. These findings provide new insights into the interaction between biomaterials and the physiological environment, which may be useful in expanding the targeted choice of efficient bone graft biodegradable materials for diabetic osteoporosis.

PLA-PEG-PLA and its electroactive tetraaniline copolymer as multi-interactive injectable hydrogels for tissue engineering.

Injectable hydrogels have served as biomimic scaffolds that provide a three-dimensional (3D) structure for tissue engineering or carriers for cell encapsulation in the biomedical field. In this study, the injectable electroactive hydrogels (IEHs) were prepared by introducing electrical properties into the injectable materials. Carboxyl-capped tetraaniline (CTA) as functional group was coupled with enantiomeric polylactide-poly(ethylene glycol)-polylactide (PLA-PEG-PLA), and the electroactive hydrogels were obtained by mixing the enantiomeric copolymers of CTA-PLLA-PEG-PLLA-CTA and CTA-PDLA-PEG-PDLA-CTA aqueous solutions. ultraviolet-visible spectroscopy (UV-vis) and cyclic voltammetry (CV) of the complex solution showed good electroactive properties. The gelation mechanism and intermolecular multi-interactions such as stereocomplextion, hydrogen bonding, and π-π stacking were studied by Fourier transform infrared spectroscopy (FT-IR), UV-vis, and wide-angle X-ray diffraction (WAXD). Gelation properties of the complexes were also studied by rheometer. The encapsulated cells remained highly viable in the gel matrices, suggesting that the hydrogels have excellent cytocompatibility. After subcutaneous injection, the gels were formed in situ in the subcutaneous layer, and hematoxylin-eosin (H&E) staining suggested acceptable biocompatibility of our materials in vivo. Moreover, these injectable materials, when treated with pulsed electrical stimuli, were shown to be functionally active and to accelerate the proliferation of encapsulated fibroblasts, cardiomyocytes, and osteoblasts. Hence, the IEHs possessing these excellent properties would be potentially used as in vivo materials for tissue engineering scaffold.

Magnetic nanocomposites for magneto-promoted osteogenesis: from simulation auxiliary design to experimental validation.

Magnetically actuated mechanical stimulation, as a novel form of intelligent responsive force stimulation, has a great potential for remote spatiotemporal regulation of a variety of life processes. Hence, the optimal design of magnetic nanomaterials for generating magneto-mechanical stimuli becomes an important driving force in the development of magneto-controlled biotherapy. This study aims to clarify the general rule that the surface modification amount of magnetic nanoparticles (NPs) affects the biological behavior (e.g., cell adhesion, proliferation and differentiation) of pre-osteoblast cells. First of all, course-grained molecular dynamics simulations predict that 23.3% graft modification of the NPs can maximize the heterogeneity of the dynamics of the polymer matrix, which may generate enhanced mechanical stimuli. Then, experimentally, iron oxide (IO) NPs grafted with different amounts of poly(γ-benzyl-L-glutamate) (PBLG) were prepared to obtain homogeneous magnetic nanocomposites with improved mechanical properties. Further in vitro cell experiments demonstrate that the grafting amounts of 21.46% and 32.34% of PBLG on IO NPs are the most beneficial for the adhesion and osteogenic differentiation of cells. Simultaneously, the maximized upregulation of the Piezo1 gene indicates that the cells receive the strongest magneto-mechanical stimuli. The consistent conclusion of the experiments and simulations indicates that 20-30% PBLG grafted on the IO surface could maximize the ability of magnetic stimuli to regulate the biological behavior of the cells, which validates the feasibility of simulation auxiliary material design and is of great importance for promoting the application of magneto-controlled biotherapy in bioengineering and biomedicine.

Conductive Polyaniline Particles Regulating In Vitro Hydrolytic Degradation and Erosion of Hydroxyapatite/Poly(lactide-co-glycolide) Porous Scaffolds for Bone Tissue Engineering.

In addition to biocompatibility and bioactivity, scaffolds with superior bone tissue regenerative capacity should possess excellent functionality (e.g., electroactivity and conductivity) and biodegradability matching with the rate of bone reconstruction. However, current conductive scaffolds display a reduced biodegradability rate and weakened biocompatibility. In this study, injectable conductive porous scaffolds were fabricated, incorporating camphor sulfonic acid-doped polyaniline (PANI) into hydroxyapatite/poly(lactide-co-glycolide) (HA/PLGA) scaffolds, using solvent-casting/particulate-leaching methodology. These scaffolds demonstrated excellent electroactivity, conductivity, hydrophilicity, thermodynamic properties, antibacterial properties, and biocompatibility. Their degradation behavior was explored by regulating the PANI content. The results demonstrated that adding an appropriate content of PANI would increase the pore size, porosity, and water absorption of the conductive scaffold and promote the formation of filamentous fiber byproducts with acidic hydrolysates, which accelerated the degradation rate of the scaffold. Owing to π-π stacking and hydrogen bonding, the conductive scaffold with 10 wt % PANI efficiently retarded the decrease in the thermal and mechanical properties of the scaffolds during a 16 week degradation. Thus, better regulation of degradation behavior and correlation would allow conductive porous scaffolds, such as bone implants, to achieve better bone ingrowth and restoration.

Synthesis of biodegradable and electroactive tetraaniline grafted poly(ester amide) copolymers for bone tissue engineering.

Biodegradable poly(ester amide)s have recently been used as biomaterials due to their desirable chemical and biological characteristics as well as their mechanical properties, which are amendable for material processing. In this study, electroactive tetraaniline (TA) grafted poly(ester amide)s were successfully synthesized and characterized. The poly(ester amide)s-graft-tetraaniline copolymers (PEA-g-TA) exhibited good electroactivity, mechanical properties, and biodegradability. The biocompatibility of the PEA-g-TA copolymers in vitro was systematically studied, which demonstrated that they were nontoxic and led to favorable adhesion and proliferation of mouse preosteoblastic MC3T3-E1 cells. Moreover, the PEA-g-TA copolymers stimulated by pulsed electrical signal could serve to promote the differentiation of MC3T3-E1 cells compared with TCPs. Hence, the biodegradable and electroactive PEA-g-TA copolymers possessed the properties in favor of the long-time potential application in vivo (electrical stimulation directly to the desired area) as bone repair scaffold materials in tissue engineering.

Nerve implants with bioactive interfaces enhance neurite outgrowth and nerve regeneration in vivo.

Nerve implants functionalized with growth factors and stem cells are critical to promote neurite outgrowth, regulate neurodifferentiation, and facilitate nerve regeneration. In this study, human umbilical cord mesenchymal stem cells (hUCMSCs) and 3,4-hydroxyphenalyalanine (DOPA)-containing insulin-like growth factor 1 (DOPA-IGF-1) were simultaneously applied to enhance the bioactivity of poly(lactide-co-glycolide) (PLGA) substrates which will be potentially utilized as nerve implants. In vitro and in vivo evaluations indicated that hUCMSCs and DOPA-IGF-1 could synergistically regulate neurite outgrowth of PC12 cells, improve intravital recovery of motor functions, and promote conduction of nerve electrical signals in vivo. The enhanced functional and structural nerve regeneration of injured spinal cord might be mainly attributable to the synergistically enhanced biofunctionality of hUCMSCs and DOPA-IGF-1/PLGA on the bioactive interfaces. Findings from this study demonstrate the potential of hUCMSC-seeded, DOPA-IGF-1-modified PLGA implants as promising candidates for promoting axonal regeneration and motor functional recovery in spinal cord injury treatment.

Tannin-bridged magnetic responsive multifunctional hydrogel for enhanced wound healing by mechanical stimulation-induced early vascularization.

Wound healing is a complex process. Wound-repair materials require multiple functionalities, such as anti-inflammatory, antibacterial, angiogenesis, pro-proliferation, and remodeling. To achieve rapid tissue regeneration, magnetic field-assisted therapy has become a promising means. In this study, a homogeneous magnetic responsive nanocomposite hydrogel with enhanced mechanical properties was obtained through a tannin (TA)-assisted bridge between magneto-deformable cobalt ferrite nanoparticles (CFO NPs) and polyvinyl alcohol (PVA) matrix. In the presence of an external static magnetic field (SMF), the TA bridge could efficiently transmit magnetically actuated deformation to the PVA, which originated from the CFO NPs, generating a larger topographic change on the surface. The change of topography provided a mechanical cue to increase cell adhesion and proliferation. Moreover, due to the synergistic effects of TA modification and CFO NPs, the obtained magnetic responsive hydrogel exhibited considerable antibacterial activity. Furthermore, the results of in vivo study confirmed the anti-inflammatory properties of the TA-CFO/PVA hydrogel. More importantly, the TA-CFO/PVA hydrogel accelerated wound healing under a SMF, which contributed to the early vascularization induced by mechanical stimuli generated from the TA-CFO/PVA nanocomposite hydrogel. As a proof-of-concept, we provided an optimizing strategy for magneto-controlled skin tissue regeneration, which may have important guiding significance for the clinical application of magnetic field-assisted therapy.

RGD-conjugated copolymer incorporated into composite of poly(lactide-co-glycotide) and poly(L-lactide)-grafted nanohydroxyapatite for bone tissue engineering.

Various surface modification methods of RGD (Arg-Gly-Asp) peptides on biomaterials have been developed to improve cell adhesion. This study aimed to examine a RGD-conjugated copolymer RGD/MPEG-PLA-PBLG (RGD-copolymer) for its ability to promote bone regeneration by mixing it with the composite of poly(lactide-co-glycotide) (PLGA) and hydroxyapatite nanoparticles surface-grafted with poly(L-lactide) (g-HAP). The porous scaffolds were prepared using solvent casting/particulate leaching method and grafted to repair the rabbit radius defects after seeding with autologous bone marrow mesenchymal cells (MSCs) of rabbits. After incorporation of RGD-copolymer, there were no significant influences on scaffold's porosity and pore size. Nitrogen of RGD peptide, and calcium and phosphor of g-HAP could be exposed on the surface of the scaffold simultaneously. Although the cell viability of its leaching liquid was 92% that was lower than g-HAP/PLGA, its cell adhesion and growth of 3T3 and osteoblasts were promoted significantly. The greatest increment in cell adhesion ratios (131.2-157.1% higher than g-HAP/PLGA) was observed when its contents were 0.1-1 wt % but only at 0.5 h after cell seeding. All the defects repaired with the implants were bridged after 24 weeks postsurgery, but the RGD-copolymer contained composite had larger new bone formation and better fusion interface. The composites containing RGD-copolymer enhanced bone ingrowth but presented more woven bones than others. The combined application of RGD-copolymer and bone morphological protein 2 (BMP-2) exhibited the best bone healing quality and was recommended as an optimal strategy for the use of RGD peptides.

A rapid quantitation of cell attachment and spreading based on digital image analysis: Application for cell affinity and compatibility assessment of synthetic polymers.

Accurate and rapid quantitation of cell attachment, spreading, and growth on a polymer thin film coated glass cover slide was developed by analyzing the digital images of cells stained with dyes. A biodegradable block copolymer poly(ethylene glycol)-block-poly(l-lactide-co-2-methyl-2-carboxyl-propylene carbonate) [PEG-b-P(LA-co-MCC)] was synthesized as model polymer with poly(L-lactic acid) [PLLA] as a control polymer. Only a small quantity of polymer (~5 mg) was needed in this method through dissolving in a solvent and casting on cover slides which were previously modified with dimethyl dichlorosilane (DMDC). Then it was seeded with cells and taken pictures with a digital camera under an optical microscope and analyzed with ImageJ software. Cell number and a series of morphological data were obtained, including cell area, circularity, perimeter and Feret's diameter, etc. The quantitative analysis results indicated that cells preferred to attach and spread on the surface of the copolymer PEG-b-P(LA-co-MCC) compared to PLLA during 24 h of cell culture. This efficient procedure provides a series of convincing statistical data to evaluate the direct interaction between cells and polymers with only an optical microscope, a digital camera and ImageJ software. It's a rapid, economic way for assessing cell affinity and compatibility of novel synthetic polymers by cell culture in vitro.

Simultaneous engineering of nanofillers and patterned surface macropores of graphene/hydroxyapatite/polyetheretherketone ternary composites for potential bone implants.

Incorporating bioactive nanofillers and creating porous surfaces are two common strategies used to improve the tissue integration of polyetheretherketone (PEEK) material. However, few studies have reported the combined use of both strategies to modify PEEK. Herein, for the first time, dual nanoparticles of graphene oxide (GO) and hydroxyapatite (HAp) were incorporated into PEEK matrix to obtain ternary composites that were laser machined to create macropores with diameters ranging from 200 µm to 600 µm on the surfaces. The surface morphology and chemistry, mechanical properties, and cellular responses of the composites were investigated. The results show that micropatterned pores with a depth of 50 µm were created on the surfaces of the composites, which do not significantly affect the mechanical properties of the resultant composites. More importantly, the incorporation of GO and HAp significantly improves the cell adhesion and proliferation on the surface of PEEK. Compared to the smooth surface composite, the composites with macroporous surface exhibit markedly enhanced cell viability. The combined use of nanofillers and surface macropores may be a promising way of improving tissue integration of PEEK for bone implants.

Ba/Mg co-doped hydroxyapatite/PLGA composites enhance X-ray imaging and bone defect regeneration.

Hydroxyapatite (HA) is the most commonly used orthopedic implant material. In recent years, the emergence of cationic doped hydroxyapatite has revealed more possibilities for the biological application of HA. Conventional HA does not promote new bone formation because of its poor osteoinductive activity, and has a similar density to that of bone, leading to difficulty in distinguishing both via imaging. Magnesium ions are useful for regulating the cellular behavior and promoting bone regeneration. Ba ion related compounds, such as BaSO4, have a strong X-ray shielding effect. In this study, Ba/Mg@HA was synthesized to prepare Ba/Mg@HA/PLGA composites, and we aimed to investigate if Ba/Mg@HA/PLGA composites enhanced bone repair on osteoblasts and tibial defects, as well as the X-ray and CT imaging ability of bone implants in rats. The in vitro experimental results showed that the Ba/Mg@HA/PLGA composites significantly improved the attachment and osteogenic differentiation of MC3T3-E1 cells. These include the promotion of mineral deposition, enhancement of alkaline phosphatase activity, upregulation of OCN and COL-1 gene expression, and increase in COL-1 and OCN protein expression in a time- and concentration-dependent manner. The in vivo experimental results showed that the Ba/Mg@HA/PLGA composites significantly increased the rate of bone defect healing and the expression of BMP-2 and COL-1 in the bones of rats. X-ray and CT imaging results showed that the Ba/Mg@HA/PLGA composites enhanced the X-ray imaging ability. These findings indicate that the Ba/Mg@HA/PLGA composites can effectively promote bone formation and improve the X-ray and CT imaging abilities to a certain extent.

EDTMP ligand-enhanced water interactions endowing iron oxide nanoparticles with dual-modal MRI contrast ability.

Single-modal magnetic resonance imaging (MRI) contrast agents sometimes cause signal confusion in clinical diagnosis. Utilizing ligands to endow iron oxide nanoparticles (IO NPs) with excellent dual-modal MRI contrast efficiency might be an effective strategy to improve diagnostic accuracy. This work presents the development of a special ligand-assisted one-pot approach for the preparation of super-hydrophilic magnetic NPs with excellent water dispersion, biocompatibility and T1-T2 dual-modal contrast enhancement properties. In addition, the strong binding capacity between the ethylenediamine tetramethylenephosphonic acid (EDTMP) ligand and water molecules induced by the presence of abundant hydrogen bonds significantly improves spin-lattice (T1) and spin-spin (T2) imaging of the IO core. After being modified with the EDTMP ligand, the T2 relaxation rate of the IO core is dramatically increased from 71.78 mM-1 s-1 to 452.38 mM-1 s-1, and a moderate T1 relaxation rate (11.61 mM-1 s-1) is observed simultaneously, implying that the NPs with an average size of 9.7 nm may be potential candidates as high-efficiency T1-T2 MRI contrast agents. This fundamental technique of using super-hydrophilicity ligands to endow IO NPs with dual-modal contrast properties without size change and damage in the T2 contrast effect may provide a useful strategy to facilitate the application of magnetic NPs in the field of medical diagnosis.

Stem Cell Seeded and Silver Nanoparticles Loaded Bilayer PLGA/PVA Dressings for Wound Healing.

Antibacterial activity and promoting wound healing are two important characteristics of ideal dressings. The previous work has successfully prepared a stem cell seeded polyvinyl alcohol (PVA) hydrogel dressing, which could promote wound healing by active factors secreted from the dressing. However, a lack of antibacterial activity might limit its better application. In this study, a photo-active gelatin (Az-Gel) modified stem cell seeded bilayer PVA hydrogel dressings with silver nanoparticles loaded poly(lactic-co-glycolic acid) (PLGA) electrospinning films (Ag-PLGA) in it is prepared. The physical properties of the dressings show the dressings are mechanically enhanced by the addition of Ag-PLGA film. The addition of Ag-PLGA film does not alter the moisture content of PVA, but extends the moisture of the dressing. Obviously, antibacterial activity is observed and Ag-PLGA/PVA scaffold is biocompatible and low toxic to murine dermal fibroblasts (NIH-3T3). When seeded with Adipose-derived stem cells (ADSCs), bioactive factors secreted by ADSCs could penetrate the dressing and promote cell growth and wound healing. It is speculated that the stem cells seeded bilayer dressing would be of great potential for skin tissue engineering, because of its antibacterial activity and safe application of stem cells.

Covalently functionalized poly(etheretherketone) implants with osteogenic growth peptide (OGP) to improve osteogenesis activity.

Polyetheretherketone (PEEK), as the most promising implant material for orthopedics and dental applications, has bone-like stiffness, excellent fatigue resistance, X-ray transparency, and near absence of immune toxicity. However, due to biological inertness, its bone conduction and bone ingrowth performance is limited. The surface modification of PEEK is an option to overcome these shortcomings and retain most of its favorable properties, especially when excellent osseointegration is desired. In this study, a simple reaction procedure was employed to bind the osteogenic growth peptide (OGP) on the surface of PEEK materials by covalent chemical grafting to construct a bioactive interface. The PEEK surface was activated by N,N'-disuccinimidyl carbonate (DSC) after hydroxylation, and then OGP was covalently grafted with amino groups. The functionalized surface of PEEK samples were characterized by X-ray photoelectron spectroscopy (XPS), Fourier-transform infrared spectroscopy (FT-IR), water contact angle measurement and biological evaluation in vitro. OGP-functionalized PEEK surface significantly promoted the attachment, proliferation, alkaline phosphatase (ALP) activity and mineralization of pre-osteoblast cells (MC3T3-E1). The in vivo rat tibia implantation model is adopted and micro-CT analyses demonstrated that the OGP coating significantly promoted new bone formation around the samples. The in vitro and in vivo results reveal that the modification by covalent chemical functionalization with OGP on PEEK surface can augment new bone formation surrounding implants compared to bare PEEK and PEEK implant modified by covalently attached OGP is promising in orthopedic and dental applications.

Gadolinium-Doped BTO-Functionalized Nanocomposites with Enhanced MRI and X-ray Dual Imaging to Simulate the Electrical Properties of Bone.

Physicochemical properties of biomaterials play a regulatory role in osteoblast proliferation and differentiation. Inspired by the electrical properties of natural bone, the electroactive composites applied to osteogenesis have gradually become the hotspot of research. In this work, an electroactive biocomposite of poly(lactic-co-glycolic acid) mixed with gadolinium-doped barium titanate nanoparticles (Gd-BTO NPs) was investigated to establish the structure-activity relationship between electrical property, especially surface potential, and osteogenic activity. Furthermore, the potential mechanism was also explored. The results showed that the introduction of Gd-BTO NPs was more conducive to improve the elastic modulus and beneficial to utilize MRI and X-ray dual imaging. The electrical characteristics of composites indicate that the introduction of Gd-BTO NPs can effectively improve the electrical properties of materials including dielectricity, piezoelectricity, and surface potential. Moreover, adjusting the amount of gadolinium doping could optimize electrical activity and enhance MRI compatibility. The surface potential of 0.2Gd-BTO/PLGA could reach -58.2 to -60.9 mV at pH values from 7 to 9. Functional studies on cells revealed that the negative surface potential of poled Gd-BTO/PLGA enhanced cell attachment and osteogenic differentiation significantly. Furthermore, the negative surface potential could induce intracellular Ca2+ ion concentration oscillation and improve osteogenic differentiation via the calcineurin/NFAT signal pathway. These findings suggest that electroactive Gd-BTO/PLGA nanocomposites may have huge potential for bone regeneration and be expected to have wide applications in the field of bone tissue engineering.