Patterned collagen films loaded with miR-133b@MBG-NH2for potential applications in corneal stromal injury repair.

Corneal stromal injury is a common surgical disease. With the development of tissue engineering materials, many artificial corneal scaffolds have been developed to replace allograft corneal transplantation and solve the problem of corneal donor shortage. However, few researchers have paid attention to corneal stromal wound healing. Herein, a nanocomposite of amino modified mesoporous bioactive glass (MBG-NH2) and microRNA-133b (miR-133b) was introduced into the patterned collagen films to achieve corneal stromal injury repair. MBG-NH2nanoparticles as a nano delivery carrier could efficiently load miR-133b and achieve the slow release of miR-133b. The physicochemical properties of collagen films were characterized and found the microgrooved collagen films loaded with miR-133b@MBG-NH2nanoparticles possessed similar swelling properties, optical clarity, and biodegradability to the natural cornea.In vitrocell experiments were also conducted and proved that the patterned collagen films with miR-133b@MBG-NH2possessed good biocompatibility, and miR-133b@MBG-NH2nanoparticles could be significantly uptake by rabbit corneal stromal cells (RCSCs) and have a significant impact on the orientation, proliferation, migration, and gene expression of RCSCs. More importantly, the patterned collagen films with miR-133b@MBG-NH2could effectively promote the migration of RCSCs and accelerate wound healing process, and down-regulate the expression levels ofα-SMA, COL-I, and CTGF genes associated with myofibroblast differentiation of corneal stromal cells, which has a potential application prospect in the repair of corneal stromal injury.

Bioactive Glasses-Based Nanozymes Composite Macroporous Cryogel with Antioxidative, Antibacterial, and Pro-Healing Properties for Diabetic Infected Wound Repair.

The treatment for diabetic ulcers still remains a big clinic challenge owing to the adverse repair microenvironment. Bioactive glasses (BGs) play an important role in the late stages of healing due to their ability to promote vascularization and collagen fiber deposition, but fail to improve infection and oxidative stress in the early stage.Therefore, it is critical to develop a material involved in regulating the whole healing phases. In this work, BGs-based nanozymes (MnO2 @PDA-BGs) with antioxidation, antibacterial and pro-healing abilities are synthesized by the redox deposition of MnO2 on mesoporous BGs. Afterward, cryogel with the interconnected macropore structure is fabricated by the polymerization of methacrylate anhydride gelatin (GelMA) at -20 °C. MnO2 @PDA-BGs are loaded into the cryogel to obtain nanocomposite cryogel (MnO2 @PDA-BGs/Gel) with multiple enzymes-like- activities to eliminate reactive oxygen species (ROS). Besides, MnO2 @PDA-BGs/Gel has intensive peroxidase-like activity under acidic condition and near infrared photothermal responsiveness to achieve excellent antibacterial performance. Cells experiments demonstrate that MnO2 @PDA-BGs/Gel recruits L929s and promotes their proliferation. Furthermore, MnO2 @PDA-BGs/Gel eliminates intracellular overexpressed ROS and maintains the viability of L929s. Animal experiments confirm that MnO2 @PDA-BGs/Gel promotes wound healing and avoided scarring by killing bacteria, reversing inflammation, promoting vascularization, and improving the deposition of collagen III.

Microenvironment responsive nanocomposite hydrogel with NIR photothermal therapy, vascularization and anti-inflammation for diabetic infected wound healing.

Bacterial infection, excessive inflammation and damaging blood vessels network are the major factors to delay the healing of diabetic ulcer. At present, most of wound repair materials are passive and can't response to the wound microenvironment, resulting in a low utilization of bioactive substances and hence a poor therapeutic effect. Therefore, it's essential to design an intelligent wound dressing responsive to the wound microenvironment to achieve the release of drugs on-demand on the basis of multifunctionality. In this work, metformin-laden CuPDA NPs composite hydrogel (Met@ CuPDA NPs/HG) was fabricated by dynamic phenylborate bonding of gelatin modified by dopamine (Gel-DA), Cu-loaded polydopamine nanoparticles (CuPDA NPs) with hyaluronic acid modified by phenyl boronate acid (HA-PBA), which possessed good injectability, self-healing, adhesive and DPPH scavenging performance. The slow release of metformin was achieved by the interaction with CuPDA NPs, boric groups (B-N coordination) and the constraint of hydrogel network. Metformin had a pH and glucose responsive release behavior to treat different wound microenvironment intelligently. Moreover, CuPDA NPs endowed the hydrogel excellent photothermal responsiveness to kill bacteria of >95% within 10 min and also the slow release of Cu2+ to protect wound from infection for a long time. Met@ CuPDA NPs/HG also recruited cells to a certain direction and promoted vascularization by releasing Cu2+. More importantly, Met@CuPDA NPs/HG effectively decreased the inflammation by eliminating ROS and inhibiting the activation of NF-κB pathway. Animal experiments demonstrated that Met@CuPDA NPs/HG significantly promoted wound healing of diabetic SD rats by killing bacteria, inhibiting inflammation, improving angiogenesis and accelerating the deposition of ECM and collagen. Therefore, Met@CuPDA NPs/HG had a great application potential for diabetic wound healing.

Platelet-Rich Plasma Gel-Loaded Collagen/Chitosan Composite Film Accelerated Rat Sciatic Nerve Injury Repair.

Peripheral nerve injury (PNI) is a common clinical disease caused by severe limb trauma, congenital malformations, and tumor resection, which may lead to significant functional impairment and permanent disability. Nerve conduit as a method for treating peripheral nerve injury shows good application prospects. In this work, the COL/CS composite films with different mass ratios of 1:0, 1:1, and 1:3 were fabricated by combining physical doping. Physicochemical characterization results showed that the COL/CS composite films possessed good swelling properties, ideal mechanical properties, degradability and suitable hydrophilicity, which could meet the requirements of nerve tissue engineering. In vitro cell experiments showed that the loading of platelet-rich plasma (PRP) gel on the surface of COL/CS composite films could significantly improve the biocompatibility of films and promote the proliferation of Schwann cells. In addition, a rat model of sciatic nerve defect was constructed to evaluate the effect of COL/CS composite films on peripheral nerve repair and the results showed that COL/CS composite films loaded with PRP gel could promote nerve regeneration and functional recovery in rats with sciatic nerve injury, indicating that the combination of PRP gel with the COL/CS composite film would be a potential approach for the treatment of peripheral nerve injury.

Effects of electroactive materials on nerve cell behaviors and applications in peripheral nerve repair.

Peripheral nerve damage can lead to loss of function or even complete disability, which brings about a huge burden on both the patient and society. Regulating nerve cell behavior and promoting nerve injury repair by bionic construction of a biological electric field to simulate natural nerve electrophysiological characteristics have attracted great attention, and many studies have shown that electroactive materials have a good repair effect on peripheral nerves. Here, we summarize the electroactive materials commonly used in peripheral nerve repair and their characteristics, especially for the design and application of a biodegradable non-invasive spontaneous electrical system. Besides, based on the fact that electroactive materials can provide electrical conductivity or a power generation performance, the specific role of electroactive materials in peripheral nerve repair was summed up from the following three aspects: cell behavior regulation, signaling pathway regulation and immune microenvironment regulation. This review provides a summary of the current research on the use of electroactive materials in peripheral nerve repair, which may help provide a more effective strategy for peripheral nerve injury (PNI) and allow more patients to benefit from artificial nerve catheter treatment.

Improving the physical quality of students by prescription teaching mode / Melhora da qualidade física dos alunos pelo método de ensino por prescrição / Mejora de la calidad física de los alumnos por el método de enseñanza por prescripción

ABSTRACT Introduction The physique of college students is very important. The physique of college students is the prerequisite for the country's revitalization, and health is the prerequisite for the transformation of intellectual capital. Object Aiming at the current college students' physical education class arrangements and curriculum reform, the paper uses exercise prescriptions to make a brief plan for students' physical exercise. Method The thesis uses the exercise prescription teaching method to carry out health intervention education for middle school students, which is used to analyze the physical requirements of students. Results After five months of fitness exercise prescription, the students' physical fitness has increased significantly. We use fitness exercise prescriptions to make students feel good about exercise. Conclusion The application of physical and healthy exercise prescriptions can effectively improve the systematic and scientific nature of students' participation in sports and help students learn and master healthy physical and mental self-exercise skills. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução O físico dos estudantes universitários é muito importante. O físico dos universitários é o pré-requisito para a revitalização do país, e a saúde é o pré-requisito para a transformação do capital intelectual. Objeto Visando os arranjos das aulas de educação física dos atuais estudantes universitários e a reforma curricular, o artigo usa prescrições de exercícios para fazer um breve plano para os exercícios físicos dos alunos. Método A tese utiliza o método de ensino da prescrição de exercícios para realizar educação de intervenção em saúde para alunos do ensino médio, que é utilizada para analisar as exigências físicas dos alunos. Resultados Após cinco meses de prescrição de exercícios físicos, a aptidão física dos alunos aumentou significativamente. Usamos prescrições de exercícios físicos para fazer os alunos se sentirem bem com os exercícios. Conclusão A aplicação de prescrições de exercícios físicos e saudáveis pode efetivamente melhorar a natureza sistemática e científica da participação dos alunos em esportes e ajudá-los a aprender e dominar habilidades saudáveis de auto-exercício físico e mental. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción El físico de los estudiantes universitarios es muy importante. El físico de los estudiantes universitarios es el requisito previo para la revitalización del país, y la salud es el requisito previo para la transformación del capital intelectual. Objeto Con el objetivo de los arreglos de las clases de educación física de los estudiantes universitarios actuales y la reforma del plan de estudios, el documento utiliza prescripciones de ejercicios para hacer un plan breve para el ejercicio físico de los estudiantes. Método La tesis utiliza el método didáctico de prescripción de ejercicios para realizar la educación de intervención en salud para estudiantes de secundaria, que se utiliza para analizar los requisitos físicos de los estudiantes. Resultados Después de cinco meses de prescripción de ejercicios físicos, la aptitud física de los estudiantes ha aumentado significativamente. Usamos recetas de ejercicios físicos para que los estudiantes se sientan bien con el ejercicio. Conclusión La aplicación de prescripciones de ejercicio físico y saludable puede mejorar de manera efectiva la naturaleza sistemática y científica de la participación de los estudiantes en los deportes y ayudar a los estudiantes a aprender y dominar habilidades saludables de autoejercicio físico y mental. Nivel de evidencia II; Estudios terapéuticos: investigación de los resultados del tratamiento.

Regulation of Myogenic Differentiation by Topologically Microgrooved Surfaces for Skeletal Muscle Tissue Engineering.

Inspired by the natural topological structure of skeletal muscle tissue, the topological surface construction of bionic scaffolds for skeletal muscle repair has attracted great interest. Many previous studies have focused on the effects of the topological structure on myoblasts. However, these studies used only specific repeating sizes and shapes to achieve the myoblast alignment and myotube formation; moreover, the regulatory effects of the size of a topological structure on myogenic differentiation are often neglected, leading to a lack of guidance for the design of scaffolds for skeletal muscle tissue engineering. In this study, we fabricated a series of microgroove topographies with various widths and depths via a combination of soft lithography and melt-casting and studied their effects on the behaviors of skeletal muscle cells, especially myogenic differentiation, in detail. Microgrooved poly(lactic-co-glycolic acid) substrates were found to effectively regulate the proliferation, myogenic differentiation, and myotube formation of C2C12 cells, and the degree of myogenic differentiation was significantly dependent on signals in response to the size of the microgroove structure. Compared with their depth, the width of the microgroove structures can more strongly affect the myogenic differentiation of C2C12 cells, and the degree of myoblast differentiation was enhanced with increasing groove width. Microgroove structures with relatively large groove widths and small groove depths promoted the myogenic differentiation of C2C12 cells. In addition, the integrin-mediated focal adhesion kinase signaling pathway and MAPK signaling pathway were activated in cells in response to the external topological structure, and the size of the topological structure of the material surface effectively regulated the degree of the cellular response to the external topological structure. These results can guide the design of scaffolds for skeletal muscle tissue engineering and the construction of effective bionic scaffold surfaces for skeletal muscle regeneration.

3D printing of Cu-doped bioactive glass composite scaffolds promotes bone regeneration through activating the HIF-1α and TNF-α pathway of hUVECs.

The increasing insight into the molecular and cellular processes within the angiogenic cascade assists in enhancing the survival and integration of engineered bone constructs. Copper-doped bioactive glass (Cu-BG) is now a potential structural component of the novel scaffolds and implants used in orthopedic and dental repairs. However, it is difficult for BG, especially micro-nano particles, to be printed into scaffolds and still retain its biological activity and ability to biodegrade. Additionally, the mechanisms of the copper-stimulating autocrine and paracrine effects of human umbilical vein endothelial cells (hUVECs) during repair and regeneration of bone are not yet clear. Therefore, in this study, we created monodispersed micro-nano spherical Cu-BG particles with varying copper content through a sol-gel process. Through in vitro tests, we found that Cu-BG enhanced angiogenesis by activating the pro-inflammatory environment and the HIF-1α pathway of hUVECs. Furthermore, 2Cu-BG diluted extracts directly promoted the osteogenic differentiation of mouse bone mesenchymal stem cells (BMSCs) in vitro. Then, a new 3D-printed tyramine-modified gelatin/silk fibroin/copper-doped bioactive glass (Gel/SF/Cu-BG) scaffold for rat bone defects was constructed, and the mechanism of the profound angiogenesis effect regulated by copper was explored in vivo. Finally, we found that hydrogel containing 1 wt% 2Cu-BG effectively regulated the spatiotemporal coupling of vascularization and osteogenesis. Therefore, Cu-BG-containing scaffolds have great potential for a wide range of bone defect repairs.

Engineering topography: effects on nerve cell behaviors and applications in peripheral nerve repair.

There have been extensive studies on the application of topography in the field of tissue repair. A common feature of these studies is that the existence of topological structures in tissue repair scaffolds can effectively regulate a series of behaviors of cells and play a positive role in a variety of tissue repair and regeneration processes. This review focuses on the application of topography in the field of peripheral nerve repair. The integration of the topological structure and biomaterials to construct peripheral nerve conduits to mimic a natural peripheral nerve structure has an important role in promoting the recovery of peripheral nerve function. Therefore, in this review, we systematically analysed the structure of peripheral nerves and summarized the effects of topographic cues of different scales and shapes on the behaviors of nerve cells, including cell morphology, adhesion, proliferation, migration and differentiation. Furthermore, the application and performance of scaffolds with different topological structures in peripheral nerve repair are also discussed. This systematic summary may help to provide more effective strategies for peripheral nerve regeneration (PNR) and shed light on nervous tissue engineering and regenerative medicine.

3D printed silk-gelatin hydrogel scaffold with different porous structure and cell seeding strategy for cartilage regeneration.

Hydrogel scaffolds are attractive for tissue defect repair and reorganization because of their human tissue-like characteristics. However, most hydrogels offer limited cell growth and tissue formation ability due to their submicron- or nano-sized gel networks, which restrict the supply of oxygen, nutrients and inhibit the proliferation and differentiation of encapsulated cells. In recent years, 3D printed hydrogels have shown great potential to overcome this problem by introducing macro-pores within scaffolds. In this study, we fabricated a macroporous hydrogel scaffold through horseradish peroxidase (HRP)-mediated crosslinking of silk fibroin (SF) and tyramine-substituted gelatin (GT) by extrusion-based low-temperature 3D printing. Through physicochemical characterization, we found that this hydrogel has excellent structural stability, suitable mechanical properties, and an adjustable degradation rate, thus satisfying the requirements for cartilage reconstruction. Cell suspension and aggregate seeding methods were developed to assess the inoculation efficiency of the hydrogel. Moreover, the chondrogenic differentiation of stem cells was explored. Stem cells in the hydrogel differentiated into hyaline cartilage when the cell aggregate seeding method was used and into fibrocartilage when the cell suspension was used. Finally, the effect of the hydrogel and stem cells were investigated in a rabbit cartilage defect model. After implantation for 12 and 16 weeks, histological evaluation of the sections was performed. We found that the enzymatic cross-linked and methanol treatment SF5GT15 hydrogel combined with cell aggregates promoted articular cartilage regeneration. In summary, this 3D printed macroporous SF-GT hydrogel combined with stem cell aggregates possesses excellent potential for application in cartilage tissue repair and regeneration.

Injectable DMEM-induced phenylboronic acid-modified hyaluronic acid self-crosslinking hydrogel for potential applications in tissue repair.

Most of traditional injectable hydrogels based on light curing or enzyme crosslinking are difficult to control the crosslinking time accurately and lack tissue adhesion, which leads to difficult clinical application and poor tissue repair effect. In this study, a novel injectable DMEM (Dulbecco's Modified Eagle's Medium)-induced phenylboronic acid-modified hyaluronic acid self-crosslinking hydrogel was designed and prepared by combining the phenylboronic acid and a diol on hyaluronic acid as the main network, in which dynamically reversible phenylboronic acid esters imparted good self-healing properties and tissue adhesion properties to the hydrogels. Cell medium that induced the formation of the hydrogel could simulate the pH of the physiological environment and provide uniform nutrients for the encapsulated cells. In addition, in vitro cell experiments indicated that the DMEM-induced phenylboronic acid-modified hyaluronic acid self-crosslinking hydrogel was capable of supporting cell loading and proliferation, thus being a promising candidate for tissue repair materials.

Manipulating Mesenchymal Stem Cell Differentiation on Nanopattern Constructed through Cell-Mediated Mineralization.

The extracellular matrix microenvironment, including chemical constituents and topological structure, plays key role in regulating the cell behavior, such as adhesion, proliferation, differentiation, apoptosis, etc. Until now, to investigate the relationship between surface texture and cell response, various ordered patterns have been prepared on the surface of different matrixes, whereas almost all these strategies depend on advanced instruments or severe synthesis conditions. Herein, cell-mediated mineralization method has been applied to construct nanopattern on the surface of ß-TCP scaffold. The formation process, morphology, and composition of the final pattern were characterized, and a possible mineralization mechanism has been proposed. Moreover, the cell behavior on the nanopattern has been investigated, and the results showed that the mouse bone marrow mesenchyme stem cells (mBMSCs) display good affinity with the nanopattern, which was manifested by the good proliferation and osteogenic differentiation status of cells. The synthetic strategy may shed light to construct advanced topological structures on other matrixes for bone repair.

Constructing a Sr2+-Substituted Surface Hydroxyapatite Hexagon-Like Microarray on 3D-Plotted Hydroxyapatite Scaffold to Regulate Osteogenic Differentiation.

Surface topography and chemical characteristics can regulate stem cell proliferation and differentiation, and decrease the bone-healing time. However, the synergetic function of the surface structure and chemical cues in bone-regeneration repair was rarely studied. Herein, a strontium ion (Sr2+)-substituted surface hydroxyapatite (HA) hexagon-like microarray was successfully constructed on 3D-plotted HA porous scaffold through hydrothermal reaction to generate topography and chemical dual cues. The crystal phase of the Sr2+-substituted surface microarray was HA, while the lattice constant of the Sr2+-substituted microarray increased with increasing Sr2+-substituted amount. Sr2+-substituted microarray could achieve the sustainable release of Sr2+, which could effectively promote osteogenic differentiation of human adipose-derived stem cells (ADSCs) even without osteogenic-induced media. Osteogenic characteristics were optimally enhanced using the higher Sr2+-substituted surface microarray (8Sr-HA). Sr2+-substituted microarray on the scaffold surface could future improve the osteogenic performance of HA porous scaffold. These results indicated that the Sr2+-substituted HA surface hexagon-like microarray on 3D-plotted HA scaffolds had promising biological performance for bone-regeneration repair scaffold.

Engineering the cellular mechanical microenvironment to regulate stem cell chondrogenesis: Insights from a microgel model.

Biophysical cues (especially mechanical cues) embedded in cellular microenvironments show a critical impact on stem cell fate. Despite the capability of traditional hydrogels to mimic the feature of extracellular matrix (ECM) and tune their physicochemical properties via diverse approaches, their relatively large size not only induces biased results, but also hinders high-throughput screening and analysis. In this paper, a microgel model is proposed to recapitulate the role of 3D mechanical microenvironment on stem cell behaviors especially chondrogenesis in vitro. The small diameter of microgels brings the high surface area to volume ratio and then the enlarged diffusion area and shortened diffusion distance of soluble molecules, leading to uniform distribution of nutrients and negligible biochemical gradient inside microgels. To construct ECM-like microenvironment with tunable mechanical strength, three gelatin/hyaluronic acid hybrid microgels with low, medium and high crosslinking densities, i.e., Gel-HA(L), Gel-HA(M) and Gel-HA(H), are fabricated in microfluidic devices by Michael addition reaction between thiolated gelatin (Gel-SH) and ethylsulfated hyaluronic acid (HA-VS) with different substitution degrees of vinyl sulfone groups. Our results show that mouse bone marrow mesenchymal stem cell (BMSC) proliferation, distribution and chondrogenesis are all closely dependent on mechanical microenvironments in microgels. Noteworthily, BMSCs show a clear trend of differentiating into hyaline cartilage in Gel-HA(L) and fibrocartilage in Gel-HA(M) and Gel-HA(H). Whole transcriptome RNA sequencing reveals that mechanical microenvironment of microgels affects BMSC differentiation via TGF-ß/Smad signaling pathway, Hippo signaling pathway and Integrin/YAP/TAZ signaling pathway. We believe this microgel model provides a new way to further explore the interaction between cells and 3D microenvironment. STATEMENT OF SIGNIFICANCE: In recent years, hydrogels have been frequently used to construct 3D microenvironment for cells. However, their relatively large size not only brings biased experimental results, but also limits high-throughput screening and analysis. Herein we propose a gelatin/hyaluronic acid microgel model to explore the effects of 3D cellular mechanical microenvironment (biophysical cues) on BMSC behaviors especially chondrogenesis, which can minimize the interference of biochemical gradients. Our results reveal that BMSC differentiation into either hyaline cartilage or fibrocartilage can be regulated via tailoring the mechanical properties of microgels. Whole transcriptome RNA sequencing proves that "TGF-ß/Smad signaling pathway", "Hippo signaling pathway" and "Integrins/YAP/ TAZ signaling pathway" are activated or inhibited in this process.

Preparation of collagen/cellulose nanocrystals composite films and their potential applications in corneal repair.

As the main component of the natural cornea, collagen (COL) has been widely applied to the construction of corneal repair materials. However, the applications of collagen are limited due to its poor mechanical properties. Cellulose nanocrystals (CNCs) possess excellent mechanical properties, optical transparency and good biocompatibility. Therefore, in this study, we attempted to introduce cellulose nanocrystals into collagen-based films to obtain corneal repair materials with a high strength. CNCs were incorporated at 1, 3, 5, 7 and 10 wt%. The physical properties of these composite films were characterized, and in vitro cell-based analyses were also performed. The COL/CNC films possessed better mechanic properties, and the introduction of CNCs did not affect the water content and light transmittance. The COL/CNC films demonstrated good biocompatibility toward rabbit corneal epithelial cells and keratocytes in vitro. Moreover, the collagen films with appropriate ration of CNCs effectively induced the migration of corneal epithelial cells and inhibited the myofibroblast differentiation of keratocytes. A collagen film with 7 wt% CNCs displayed the best combination of physical properties and biological performance in vitro among all the films. This study describes a nonchemical cross-linking method to enhance the mechanical properties of collagen for use in corneal repair materials and highlights potential application in corneal tissue engineering.

Engineered macroporous hydrogel scaffolds via pickering emulsions stabilized by MgO nanoparticles promote bone regeneration.

Hydrogels are appealing biomaterials for regenerative medicine since biomimetic modifications of their polymeric network can provide unique physical properties and emulate the native extracellular matrix (ECM). Meanwhile, therapeutic metal ions, such as magnesium ions (Mg2+), not only regulate cellular behaviours but also stimulate local bone formation and healing. However, the absence of a meaningful macroporous structure and the uncompromising mechanical strength are still challenges. Herein, we designed a macroporous composite hydrogel based on mild and fast thiol-ene click reactions. The Pickering emulsion method was adopted to form a macroporous structure and introduce MgO nanoparticles (NPs). The results show that the composite hydrogel possesses good mechanical strength and an evenly distributed macroporous structure. MgO NPs stabilized at the oil/water interface not only function as effective emulsion stabilizers, but also enhance the mechanical properties of hydrogels and mediate the sustained release of Mg2+. In vitro cell experiments demonstrated that the composite hydrogel displays good biocompatibility. More importantly, the release of Mg2+ ions from hydrogels can effectively promote the osteogenic differentiation of BMSCs. Furthermore, an in vivo study showed that macroporous hydrogels can provide a good extracellular matrix microenvironment for in situ osteogenesis and accelerate bone tissue regeneration.

Nanochitin/metal ion dual reinforcement in synthetic polyacrylamide network-based nanocomposite hydrogels.

Nanocomposite hydrogels consisting of a synthetic matrix reinforced by nanosized crystalline polysaccharides offer significant potential in various fields. Different from nanocellulose, the combination of nanochitin with synthetic polymers to obtain nanocomposite hydrogels has not been extensively and systematically studied. Herein, a physically and chemically dual crosslinked nanocomposite hydrogel was successfully synthesized, where chitin nanowhiskers (ChNWs) and Zn2+ were incorporated within polyacrylamide (PAAm) matrix. Nanochitin/metal ion dual reinforcement imparts increased elasticity, enhanced mechanical properties, and improved recovery performance to PAAm network. The PAAm/ChNWs/Zn2+ hydrogel could be stretched to over 13 times its original length with tensile strength of 321.9 ±â€¯8.2 kPa, and restore its original shape rapidly even when compressed at a strain of 95% with a corresponding compressive strength of 6.95 ±â€¯0.20 MPa. The multiple crosslinks and interactions among ChNWs, Zn2+ and synthetic polymeric network were investigated. Moreover, the hydrogel was applied in drug release and soft bioelectronics.

On-demand storage and release of antimicrobial peptides using Pandora's box-like nanotubes gated with a bacterial infection-responsive polymer.

Background: Localized delivery of antimicrobial agents such as antimicrobial peptides (AMPs) by a biomaterial should be on-demand. Namely, AMPs should be latent and biocompatible in the absence of bacterial infection, but released in an amount enough to kill bacteria immediately in response to bacterial infection. Methods: To achieve the unmet goal of such on-demand delivery, here we turned a titanium implant with titania nanotubes (Ti-NTs) into a Pandora's box. The box was loaded with AMPs (HHC36 peptides, with a sequence of KRWWKWWRR) inside the nanotubes and "closed" (surface-modified) with a pH-responsive molecular gate, poly(methacrylic acid) (PMAA), which swelled under normal physiological conditions (pH 7.4) but collapsed under bacterial infection (pH ≤ 6.0). Thus, the PMAA-gated Ti-NTs behaved just like a Pandora's box. The box retarded the burst release of AMPs under physiological conditions because the gate swelled to block the nanotubes opening. However, it was opened to release AMPs to kill bacteria immediately when bacterial infection occurred to lowering the pH (and thus made the gate collapse). Results: We demonstrated such smart excellent bactericidal activity against a panel of four clinically important bacteria, including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus. In addition, this box was biocompatible and could promote the osteogenic differentiation of human mesenchymal stem cells. Both in vitro and in vivo studies confirmed the smart "on-demand" bactericidal activity of the Pandora's box. The molecularly gated Pandora's box design represents a new strategy in smart drug delivery.

A Dexamethasone-Eluting Porous Scaffold for Bone Regeneration Fabricated by Selective Laser Sintering.

Additive manufacture (AM) has been widely and rapidly applied in fabrication of 3D porous scaffolds for tissue engineering applications. For synthetic polymers of high melting temperature, the melting-extruding technique is the most applied AM method for such fabrication of polymer porous scaffolds. This results in a big challenge to directly process the scaffolds using the polymers and thermosensitive substances simultaneously because of deactivation under high temperature. In this article, the selective laser sintering (SLS) method was proposed to make a poly(l-lactic acid) (PLLA) porous scaffold containing dexamethasone (Dex) simultaneously. Dex was encapsulated in two groups of PLLA-bioactive glass (BG) composite microspheres with an average diameter of 115-120 µm and loading amounts of 0.68 ± 0.09 and 0.84 ± 0.10 µg/mg, respectively. The drug-loading composite microspheres were then fabricated into scaffolds under a laser fluence of 0.83-2.08 J/mm2. The average pore size and compressive modulus for the porous scaffold were 450-500 µm and 18-25 MPa, respectively. Drug release experiments showed that Dex was released from the scaffold in a controlled manner until about a month. The eluting time of HPLC tests before or after SLS processing both presented at 4 min indicated no chemical structure changes for the drug. Ex vivo cell experiments also testified the comparable effect of released Dex with commercial products, showing that the bioactivities were not affected after SLS. Implantation of the composite scaffolds in rat cranium defects demonstrated that new bone and blood vessel formation was faster in the Dex-releasing scaffolds than in the groups without drug loading.

In Situ Formation of Hexagon-like Column Array Hydroxyapatite on 3D-Plotted Hydroxyapatite Scaffolds by Hydrothermal Method and Its Effect on Osteogenic Differentiation.

In the preparation of bioactive bone graft materials, surface topography is essential for the ultimate stem cell response. However, the tunable fabrication of surface topography for 3D bioceramic scaffolds is still a technical problem because of the low processability and high brittleness of bioceramics. In this study, an evenly spaced hexagon-like column array surface was fabricated in situ via a hydrothermal method on 3D plotted hydroxyapatite scaffolds. Compared with the Control scaffolds, hydroxyapatite scaffolds with a hexagon-like column array topography possessed a higher crystal orientation degree and specific surface area, which further enhanced fibronectin adsorption. The array topography on the hydroxyapatite scaffolds also showed good biocompatibility with human adipose-derived stem cells (ADSCs). More importantly, the Array scaffolds significantly promoted the expression levels of osteogenic-related genes and proteins compared with the Control scaffolds. The results suggested that the construction of hexagon-like column array topography might be critical for the design of bone regeneration scaffolds with spontaneous stimulation capacity.