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Excessive scar formation caused by cutaneous injury leads to pruritus, pain, contracture, dyskinesia, and unpleasant appearance. Functional wound dressings are designed to accelerate wound healing and reduce scar formation. In this study, we fabricated aligned or random polycaprolactone/silk fibroin electrospun nanofiber membranes with or without lovastatin loading, and then evaluated their scar-inhibitory effects on wounds under a specific tension direction. The nanofiber membranes exhibited good controlled-release performance, mechanical properties, hydrophilicity, and biocompatibility. Furthermore, nanofibers' perpendicular placement to the tension direction of the wound most effectively reduced scar formation (the scar area decreased by 66.9%) and promoted skin regeneration in vivo. The mechanism was associated with aligned nanofibers regulated collagen organization in the early stage of wound healing. Moreover, lovastatin-loaded nanofibers inhibited myofibroblast differentiation and migration. Both tension direction-perpendicular topographical cues and lovastatin synergistically inhibited mechanical transduction and fibrosis progression, further reducing scar formation. In summary, our study may provide an effective scar prevention strategy in which individualized dressings can be designed according to the local mechanical force direction of patients' wounds, and the addition of lovastatin can further inhibit scar formation. In vivo, cells and collagen are always arranged parallel to the tension direction. However, the aligned topographic cues themselves promote myofibroblast differentiation and exacerbate scar formation. Electrospun nanofibers' perpendicular placement to the tension direction of the wound most effectively reduces scar formation and promotes skin regeneration in vivo. The mechanism is associated with tension direction-perpendicular nanofibers reregulate collagen organization in the early stage of wound healing. In addition, tension direction-perpendicular topographical cue and lovastatin could inhibit mechanical transduction and fibrosis progression synergistically, further reducing scar formation. This study proves that combining topographical cues of wound dressing and drugs would be a promising therapy for clinical scar management. [Display omitted] [ABSTRACT FROM AUTHOR]

The treatment and repair of large bone defects remains a major therapeutic challenge in the clinical setting. Nanofiber scaffolds fabricated via the electrospinning technique have been developed as a universal method for bone regeneration due to their suitable properties. However, traditional two-dimensional (2D) nanofiber mats are usually too dense, which may prevent cell infiltration and growth, thereby restricting their application. Herein, a three-dimensional (3D) polycaprolactone nanofiber scaffold was developed, modified by biomineralization and silk fibroin coating. The scaffold possessed a parallel array of nanofiber surfaces, mimicking the parallel structure of fibrils in natural bone tissue. Furthermore, the fabricated radially or laterally interconnected macrochannels were investigated to elucidate the effect of the scaffold structure on bone regeneration. In vitro studies revealed that the scaffolds could guide cell arrangement and that the radially aligned scaffold demonstrated a stronger ability to promote cell proliferation. In vivo results showed that the radially aligned scaffold could guide tissue arrangement and remodeling and support a significantly faster regeneration rate of bone tissue. Therefore, 3D-mineralized polycaprolactone nanofiber scaffolds with radially interconnected macrochannels and aligned nanofibers are expected to be used in tissue engineering, including in the repair of bone defects, cartilage or other composite tissues. [ABSTRACT FROM AUTHOR]

For a class of systems who suffers from disturbances, an original output feedback sliding mode control method is presented based on a novel tracking error observer with disturbance estimator. The mathematical models of the systems are not required to be with high accuracy, and the disturbances can be vanishing or nonvanishing, while the bounds of disturbances are unknown. By constructing a differential sliding surface and employing reaching law approach, a sliding mode controller is obtained. On the basis of an extended disturbance estimator, a creative tracking error observer is produced. By using the observation of tracking error and the estimation of disturbance, the sliding mode controller is implementable. It is proved that the disturbance estimation error and tracking observation error are bounded, the sliding surface is reachable and the closed-loop system is robustly stable. The simulations on a servomotor positioning system and a five-degree-of-freedom active magnetic bearings system verify the effect of the proposed method. [ABSTRACT FROM AUTHOR]

Although various strategies have been utilized to accelerate bone regeneration in bone tissue engineering (BTE), the treatment and repair of large bone defects remains a clinical challenge worldwide. Inspired by the natural extracellular matrix of bone tissue, organic-inorganic composite scaffolds with three-dimensional (3D) porous structures, sufficient mechanical properties, excellent cytocompatibility, osteoconductivity, and osteogenic potential have received considerable attention within the field of bone engineering. In this work, a novel epichlorohydrin (ECH)-crosslinked hydroxyethyl cellulose (HEC)/soy protein isolate (SPI) porous bi-component scaffold (EHSS) with hydroxyapatite (HAp) functionalization (EHSS/HAp) was constructed for bone defect repair via the combination of lyophilization and in situ biomimetic mineralization. Systematic characterization experiments were performed to assess the morphology, HAp-forming properties, mechanical properties and degradation rate of the scaffold. The results indicated that the prepared scaffolds exhibited an interconnected porous structure, a biomimetic HAp coating on their surfaces, improved mechanical properties in compression and a controllable degradation rate. In particular, semiquantitative analysis showed that the calcium/phosphorus (Ca/P) ratio of EHSS/HAp with 70% SPI content (1.65) was similar to that of natural bone tissue (1.67) according to energy dispersive X-ray spectroscopy analysis. In vitro cell culture experiments indicated that the EHSS/HAp with 70% SPI content showed improved cytocompatibility and was suitable for MC3T3-E1 cell attachment, proliferation and growth. Consistently, in vitro osteogenic differentiation studies showed that EHSS/HAp with 70% SPI content can significantly accelerate the expression of osteogenesis-related genes (Col-1, Runx2, OPN, and OCN) during osteogenic differentiation of MC3T3-E1 cells. Furthermore, when applied to the repair of critical-sized cranial defects in a rat model, EHSS/HAp with 70% SPI was capable of significantly promoting tissue regeneration and integration with native bone tissue. Microscopic computed tomography (micro-CT) results demonstrated that the bone defect site was nearly occupied with newly formed bone at 12 weeks after implantation of EHSS/HAp with 70% SPI content into the defect. Hematoxylin and eosin (H&E) staining and Masson's trichrome staining of histological sections further confirmed that EHSS/HAp with 70% SPI markedly promoted new bone formation and maturation. Collectively, our results demonstrate the potential of EHSS/HAp scaffolds with 70% SPI for successful bone defect repair and regeneration. [ABSTRACT FROM AUTHOR]

[Display omitted] • Propose a preparation method for 3D-printed bioceramics with immunomodulation, angiogenesis, and osteogenesis. • Finding that 3D-printed bioceramics have excellent mineralization properties. • Finding that 3D-printed bioceramic scaffolds can solve implant migration and ectopic osteogenesis of DBM. • 3D-printed bioceramics have excellent biosafety, immunomodulation, angiogenesis, and osteogenesis. Personalized repair of bone defects remains a tremendous clinical challenge. Developing 3D-printed bioceramics with excellent osteogenic potential is an effective therapeutic strategy to overcome this challenge. In this study, we prepared composite bioceramics (designated as CSC-DBM) with immunomodulatory, vascularization, and osteogenesis based on calcium silicate (CS) bioceramics, calcium sulfate (CSH), and decalcified bone matrix (DBM). CSC-DBM bioceramics has an unmatched biomineralization potential due to the synergistic promotion of CS and CSH. Meanwhile, CSC-DBM bioceramics could effectively modulate the immune response, induce M2 macrophage polarization, promote vascular regeneration, and further enhance new bone formation. In summary, this composite bioceramics made of CS bioceramics, CSH, and DBM can provide a new solution for bone defect repair in the clinic. [ABSTRACT FROM AUTHOR]

[Display omitted] • Propose a high porosity bioglass preparation method. • Finding bioglass enhances mild magnetothermal therapy. • The mechanism relies on calcium ions during glass degradation. • The composite scaffold has superior biosafety and osteogenic effect. Bone defects and tumor cell residues after bone tumor resection have always been a challenge. We tried to investigate a kind of bioglass with both bone repair and tumor killing capability to achieve two birds with one stone. We used a Sol-Gel method to prepare the high porous magnetic bioglass (MBG) and then compounded the MBG with calcium sulfate (CS) bone cement to form the composite scaffold (CS-MBG). We found that the CS-MBG could reach about 43 °C under the condition of magnetic field in vitro. Under this condition, CS-MBG would release Ca2+ resulting in the cell death of calcium overload. Meanwhile, the suitable pH and osteogenic activity of CS-MBG can promote the postoperative bone repair and inhibit the growth of bone tumors. Our work has innovatively designed a magnetic bioglass and verified its mechanism of synergistic hyperthermia against tumor, providing a new idea for the treatment of tumor bone defects with magnetic bioglass. [ABSTRACT FROM AUTHOR]

[Display omitted] • A biomimetic strategy is presented to fabricate highly bioactive hybrid nanocomposite scaffolds via vacuum impregnation and in situ free radial polymerization. • The resulting biohybrid scaffold possessed not only a multilevel structure in the nano (nanoparticles)-micro (open pores)-macro (scaffold) but also satisfactory physicochemical properties, which was beneficial to bone regeneration. • The resulting biohybrid scaffold significantly promoted cell behaviors, including cell adhesion, proliferation, spreading, and differentiation during osteogenesis and angiogenesis. • The biohybrid nanocomposites with a robust ability to facilitate new bone formation and vascularization offer a promising alternative as bone substitutes for vascularized bone regeneration. Bioinspired materials with dual capabilities of pro-osteogenesis and pro-angiogenesis have attracted increasing scientific interest in the field of orthopedics. Herein, inspired by the mineralization process of natural bone, a biomimetic strategy is presented to fabricate highly bioactive hybrid nanocomposite scaffolds via impregnation of Si-containing polymer-induced liquid precursor (PILP) into biocompatible porous gelatin scaffolds followed by in situ free radial polymerization. The well-designed biohybrid scaffold exhibited not only a micro/nano fiber-like porous architecture (pore size: 100–200 μm; porosity: 80–90 %), high specific surface area (≈20 m2/g), vastly improved mechanical performance, tunable swelling and degradation behaviors but also a sustained release profile of bioactive Si ions up to 21 days. In vitro experiments revealed the excellent biological performance of the resulting biohybrid scaffold, including good biomineralization capacity and biocompatibility, establishing a favorable microenvironment for facilitating cell adhesion, proliferation, migration, osteogenic differentiation, and vascularization. In rat calvarial critical-size defect models, the newly developed biohybrid scaffold could potentially trigger a chain of biological events: stimulating the polarization of M2 macrophages, recruiting endogenous stem cells and endothelial cells at the injury site to enable a suitable regenerative microenvironment for accelerating coupled osteogenesis and angiogenesis, and eventually promoting vascularized bone regeneration. [ABSTRACT FROM AUTHOR]

[Display omitted] • Montmorillonite-modified nanocomposites were successfully developed using a combination of blending, crosslinking and freeze-drying processes. • Owing to the strong interfacial interaction between nanoclay and polymer chains, the nanocomposites exhibited improved physicochemical and biological properties within the ideal range for bone tissue engineering. • The addition of montmorillonite significantly promoted cell behaviors, including cell adhesion, proliferation, spreading, and differentiation, during osteogenesis. • The nanocomposites with a robust ability to facilitate new bone formation offered a promising alternative as bone substitutes for bone tissue engineering. Biomimetic organic-inorganic nanocomposite scaffolds represent a tremendous opportunity to accelerate bone regeneration due to their excellent structural and biological cues. However, the tradeoffs between biodegradability, mechanical strength, porosity and pore size, and bioactivity of the tissue-engineered nanocomposites remain a challenge. To this end, we constructed a novel biodegradable nanocomposite scaffold by chemical crosslinking of hydroxyethyl cellulose (HEC)/soy protein isolate (SPI) and montmorillonite (MMT) modification. Owing to the strong interfacial interaction between nanoclay and polymer chains, the prepared nanocomposites showed enhanced mechanical and physical properties, within the ideal range for bone tissue engineering. Furthermore, sustained sequential release of Ca and Mg ions during the degradation of the nanocomposites provided essential signaling cues for guiding bone regeneration. It was verified in vitro that the engineered nanocomposites possessed satisfactory cytocompatibility, offering a highly desirable microenvironment for cellular behaviors, including adhesion, proliferation, and spreading, as well as promoting the mineralization and osteoblastic differentiation of rat bone marrow stem cells. Notably, when employed to repair critical-sized cranial defects in rat models, the nanocomposites demonstrated not only reliable biosafety but also significant osteointegration and bone-forming ability in vivo. Collectively, our results confirmed that the incorporation of inorganic MMT nanosheets into biocompatible HEC/SPI scaffolds is a viable strategy for fabricating a suitable biomaterial that enhances the regeneration of large bone defects. [ABSTRACT FROM AUTHOR]