High-accuracy wide-range refractive index demodulation based on under-sampled fiber F-P cavity length spectrum.

A scheme of fiber Fabry-Perot (F-P) cavity refractive index (RI) demodulation named under-sampled length spectrum retrieval (ULSR) is proposed. Unlike the wavelength spectrum method, ULSR can be used for physical quantity detection with just a monochromatic laser and photodetectors, avoiding the need for wideband lasers or expensive infrared spectrometers. Eight F-P cavities of different lengths were fabricated to sample the cavity length spectrum, and then the obtained under-sampled length spectrum was used to demodulate the RI of F-P cavity fillings. It was demonstrated that the ULSR system can achieve an index measurement accuracy of 1 × 10-4 in the glucose solution index range of 1.3294-1.3746 at wavelength λ = 1.55 µm. An index demodulation with higher accuracy and wider range is expected when more than 8 F-P cavities are used. The proposed scheme, with advantages of low system complexity, low cost, high reliability, high detecting accuracy, and wide detecting range, holds great promise for facilitating the wide application of F-P cavity sensors. Additionally, ULSR liberates wavelength freedom, making it a strong candidate for multiplexed sensing based on wavelength division multiplexing.

An electrospun scaffold functionalized with a ROS-scavenging hydrogel stimulates ocular wound healing.

Ocular alkali burn is a serious ophthalmic emergency. Highly penetrative alkalis cause strong inflammatory responses leading to persistent epithelial defects, acute corneal perforation and severe scarring, and thereby persistent pain, loss of vision and cicatricial sequelae. Early and effective anti-inflammation management is vital in reducing the severity of injury. In this study, a double network biomaterial was prepared by compounding electrospinning nanofibres of thioketal-containing polyurethane (PUTK) with a reactive oxygen species (ROS)-scavenging hydrogel (RH) fabricated by crosslinking poly(poly(ethylene glycol) methyl ether methacrylate-co-glycidyl methacrylate) with thioketal diamine and 3,3'-dithiobis(propionohydrazide). The developed PUTK/RH patch exhibited good transparency, high tensile strength and increased hydrophilicity. Most importantly, it demonstrated strong antioxidant activity against H2O2 and 2,2-di(4-tert-octylphenyl)-1-picryl-hydrazyl (DPPH). Next, a rat corneal alkali burn model was established, and the PUTK/RH patch was transplanted on the injured cornea. Reduced inflammatory cell infiltration was revealed by confocal microscopy, and lower expression levels of genes relative to inflammation, vascularization and scarring were identified by qRT-PCR and western blot. Fluorescein sodium dyeing, hematoxylin and eosin (H&E) staining and immunohistochemical staining confirmed that the PUTK/RH patch could accelerate corneal wound healing by inhibiting inflammation, promoting epithelial regeneration and decreasing scar formation. STATEMENT OF SIGNIFICANCE: Ocular alkali burn is a serious ophthalmic emergency, characterized with persistent inflammation and irreversible vision loss. Oxidative stress is the main pathological process at the acute inflammatory stage, during which combined use of glucocorticoids and amniotic membrane transplantation is the most widely accepted treatment. In this study, we fabricated a polyurethane electrospun nanofiber membrane functionalized with a ROS-scavenging hydrogel. This composite patch could be a promising amniotic membrane substitute, possessing with a transparent appearance, elasticity and anti-inflammation effect. It could be easily transplanted onto the alkali-burned corneas, resulting in a significant inhibition of stromal inflammation and accelerating the recovery of corneal transparency. The conception of ROS-scavenging wound patch may offer a new way for ocular alkali burn.

A broad-spectrum antibacterial and tough hydrogel dressing accelerates healing of infected wound in vivo.

Infection can disturb the wound healing process and lead to poor skin regeneration, chronic wound, septicemia and even death. To combat the multi-drug resistance bacteria or fungi, it is urgent and necessary to develop advanced antimicrobial wound dressings. In this study, a composite hydrogel dressing composed of polyvinyl alcohol (PVA), agarose, glycerol and antibacterial hyperbranched polylysine (HBPL) was prepared by a freeze-thawing method. The hydrogel showed robust mechanical properties, and the HBPL in the hydrogel displayed effective and broad-spectrum antimicrobial properties to bacteria and fungi as well as biofilms. The composite hydrogel exhibited good biocompatibility with respect to the levels of cells, blood, tissue and main organs. In an animal experiment of an infected wound model, the hydrogel significantly eliminated the infection and accelerated the wound regeneration with better tissue morphology and angiogenesis. The hydrogel also successfully achieved scalable production of over 600 g with a yield over 90 %, suggesting the great potential for the application in practice.

A nanofibrous membrane loaded with doxycycline and printed with conductive hydrogel strips promotes diabetic wound healing in vivo.

Patients with diabetes suffer from a variety of complications and easily develop diabetic chronic wounds. The microenvironment of diabetic wounds is characterized by an excessive amount of reactive oxygen species (ROS) and an imbalance of proinflammatory and anti-inflammatory cells/factors, which hinder the regeneration of chronic wounds. In the present study, a wound dressing with immunomodulation and electroconductivity properties was prepared and assayed in vitro and in vivo. [2-(acryloyloxy) ethyl] Trimethylammonium chloride (Bio-IL) and gelatin methacrylate (GelMA) were 3D printed onto a doxycycline hydrochloride (DOXH)-loaded and ROS-degradable polyurethane (PFKU) nanofibrous membrane, followed by UV irradiation to obtain conductive hydrogel strips. DOXH was released more rapidly under a high ROS environment. The dressing promoted migration of endothelial cells and polarization of macrophages to the anti-inflammatory phenotype (M2) in vitro. In a diabetic rat wound healing test, the combination of conductivity and DOXH was most effective in accelerating wound healing, collagen deposition, revascularization, and re-epithelialization by downregulating ROS and inflammatory factor levels as well as by upregulating the M2 macrophage ratio. STATEMENT OF SIGNIFICANCE: The microenvironment of diabetic wounds is characterized by an excessive amount of reactive oxygen species (ROS) and an imbalance of proinflammatory and anti-inflammatory cells/factors, which hinder the regeneration of chronic wounds. Herein, a wound dressing composed of a DOXH-loaded ROS-responsive polyurethane membrane and 3D-printed conductive hydrogel strips was prepared, which effectively accelerated skin regeneration in diabetic wounds in vivo with better epithelialization, angiogenesis, and collagen deposition. DOXH regulated the dysfunctional wound microenvironment by ROS scavenging and polarizing macrophages to M2 phenotype, thereby playing a dominant role in diabetic wound regeneration. This design may have great potential for preparing other similar materials for the therapy of other diseases with excessive inflammation or damage to electrophysiological organs, such as nerve defect and myocardial infarction.

Antifouling poly(PEGMA) grafting modified titanium surface reduces osseointegration through resisting adhesion of bone marrow mesenchymal stem cells.

As an alternative strategy to achieve the desired bone augmentation, tenting screw technology (TST) has considerably broadened the indications for implant treatment. Titanium tenting screws are typically used in TST to maintain the space for bone regeneration. However, a high degree of osteogenic integration complicate titanium tenting screw removal and impact the bone healing micro-environment. Previous efforts have been focused on modifying titanium surfaces to enhance osseointegration while ignoring the opposite process. Due to the vital role of bone marrow mesenchymal stem cells (BMSCs) in bone regeneration, it might be feasible to reduce osseointegration around titanium tenting screws by resisting the adhesion of BMSCs. Herein, poly(ethylene glycol)methyl ether methacrylate (poly(PEGMA)) with an optimal length of PEG chain was incorporated with a Ti surface in terms of surface-initiated activators regenerated by electron transfer atom transfer radical polymerization (SI-ARGET ATRP). The cell apoptosis analysis showed that the new surface would not induce the apoptosis of BMSCs. Then, the adhesive and proliferative behaviors of BMSCs on the surface were analyzed which indicated that the poly(PEGMA) surface could inhibit the proliferation of BMSCs through resisting the adhesion process. Furthermore, in vivo experiments revealed the presence of the poly(PEGMA) on the surface resulted in a lower bone formation and osseointegration compared with the Ti group. Collectively, this dense poly(PEGMA) surface of Ti may serve as a promising material for clinical applications in the future. STATEMENT OF SIGNIFICANCE: The poly(ethylene glycol)methyl ether methacrylate (poly(PEGMA)) with an optimal length of PEG chain was grafted onto a Ti surface by surface-initiated activators regenerated by electron transfer atom transfer radical polymerization (SI-ARGET ATRP). The PEGMA surface could reduce the osteogenic integration by preventing the adhesion of cells, resulting in a lower pullout force of the modified implant and thereby desirable and feasible applications in dental surgery.

Promoting the healing of infected diabetic wound by an anti-bacterial and nano-enzyme-containing hydrogel with inflammation-suppressing, ROS-scavenging, oxygen and nitric oxide-generating properties.

The diabetic wound is easily to develop into a chronic wound because of the extremely serious and complex inflammatory microenvironment including biofilm formation, over-expressed reactive oxygen species (ROS), hypoxia and insufficiency of nitric oxide (NO) synthesis. In this work, a multifunctional hydrogel was designed and prepared by crosslinking hydrophilic poly(PEGMA-co-GMA-co-AAm) (PPGA) polymers with hyperbranched poly-L-lysine (HBPL)-modified manganese dioxide (MnO2) nanozymes. Pravastatin sodium, which is supposed to participate in the synthesis of NO, was further loaded to obtain the HMP hydrogel. The capabilities of this hydrogel in scavenging different types of ROS, generating O2, killing broad spectrum bacteria, and protecting cells against oxidative stress were confirmed in vitro. The transcriptome analysis revealed that HBPL inhibited bacterial quorum sensing (QS) system, downregulated virulent genes, and interfered bacterial metabolism. The HBPL-crosslinked hydrogels killed up to 94.1%-99.5% of methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli (E. coli) and Pseudomonas aeruginosa even at 109 CFU/mL. HBPL modification greatly increased the stability of MnO2 nanosheets in physiological environment. The MRSA-caused infection was effectively treated by the HBPL-crosslinked HMP hydrogel in vivo, and thereby the wound closure at inflammatory phase was promoted significantly. The treatment of HMP hydrogel reduced the ROS degree and relieved the inflammatory level significantly, accompanied by the decreased neutrophil infiltration and enhanced M2-type macrophage polarization in vivo. Significantly lower levels of inflammatory factors such as interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α) and chemokines-1 (CXCL-1), and higher levels of anti-inflammatory cytokines such as IL-4 and IL-10 were also confirmed. Moreover, the HMP hydrogel could promote the secretion of transforming growth factor-ß (TGF-ß) and stimulate neovascularization, and deposition of collagen with a thicker skin and epithelium structure.

A tough synthetic hydrogel with excellent post-loading of drugs for promoting the healing of infected wounds in vivo.

Bacterial infection is a major obstacle to the wound healing process. The hydrogel dressings with a simpler structure and good antibacterial and wound healing performance are appealing for clinical application. Herein, a robust hydrogel was synthesized from acrylamide (AM), acrylic acid (AA) and N,N'-methylene diacrylamide (MBA) via a redox initiating polymerization. The polymerization conditions were optimized to obtain the hydrogel with minimum unreacted monomers, which were 0.25% and 0.12% for AM and AA, respectively. The hydrogel had good mechanical strength, and could effectively resist damage by external forces and maintain a good macroscopic shape. It showed large water uptake capacity, and could post load a wide range of molecules via hydrogen bonding and electrostatic interaction. Loading of antibiotic doxycycline (DOX) enabled the hydrogel with good antibacterial activity against both Gram-positive bacteria and Gram-negative bacteria in vitro and in vivo. In a rat model of methicillin-resistant Staphylococcus aureus (MRSA)-infected full-thickness skin defect wound, the DOX-loaded hydrogel showed good therapeutic effect. It could significantly promote the wound closure, increased the collagen coverage area, down-regulate the expressions of pro-inflammatory TNF-α and IL-1ß factors, and up-regulate the expressions of anti-inflammatory IL-4 factor and CD31 neovascularization factor.

Multifunctional elastomer cardiac patches for preventing left ventricle remodeling after myocardial infarction in vivo.

Myocardial infarction (MI) is still a major cause of mortality and morbidity worldwide. Elastomer cardiac patches have shown great potential in preventing left ventricle (LV) remodeling post-MI by providing mechanical support to the infarcted myocardium. Improved therapeutic outcomes are expected by mediating pathological processes in the necrosis phase, inflammation phase, and fibrosis phase, through orchestrated biological and mechanical treatments. In this study, a mechanically robust multifunctional cardiac patch integrating reactive oxygen species (ROS)-scavenging, anti-inflammatory, and pro-angiogenic capabilities was developed to realize the integrative strategy. An elastomeric polyurethane (PFTU) containing ROS-sensitive poly (thioketal) (PTK) and unsaturated poly (propylene fumarate) (PPF) segments was synthesized, which was further clicked with pro-angiogenic Arg-Glu-Asp-Val (REDV) peptides to obtain PFTU-g-REDV (PR), and was formulated into a macroporous patch containing rosuvastatin (PRR). The mechanical support and multifunctional effects of the patch were confirmed in a rat MI model in vivo compared to the patches with only mechanical support, leading to reduced cell apoptosis, suppressed local inflammatory response, alleviated fibrosis, and induced angiogenesis. The cardiac functions and LV morphology were also well maintained. These results demonstrate the advantages of the integrated and orchestrated treatment strategy in MI therapy.

A cell-free ROS-responsive hydrogel/oriented poly(lactide-co-glycolide) hybrid scaffold for reducing inflammation and restoring full-thickness cartilage defectsin vivo.

The modulation of inflammation in tissue microenvironment takes an important role in cartilage repair and regeneration. In this study, a novel hybrid scaffold was designed and fabricated by filling a reactive oxygen species (ROS)-scavenging hydrogel (RS Gel) into a radially oriented poly(lactide-co-glycolide) (PLGA) scaffold. The radially oriented PLGA scaffolds were fabricated through a temperature gradient-guided phase separation and freeze-drying method. The RS Gel was formed by crosslinking the mixture of ROS-responsive hyperbranched polymers and biocompatible methacrylated hyaluronic acid (HA-MA). The hybrid scaffolds exhibited a proper compressive modulus, good ROS-scavenging capability, and cell compatibility.In vivotests showed that the hybrid scaffolds significantly regulated inflammation and promoted regeneration of hyaline cartilage after they were implanted into full-thickness cartilage defects in rabbits for 12 w. In comparison with the PLGA scaffolds, the neo-cartilage in the hybrid scaffolds group possessed more deposition of glycosaminoglycans and collagen type II, and were well integrated with the surrounding tissue.

Stimuli-Sensitive Nanotherapies for the Treatment of Osteoarthritis.

Osteoarthritis (OA) is a common chronic inflammatory disease in the joints. It is one of the leading causes of disability with increasing morbidity, which has become one of the serious clinical issues. Current treatments would only provide temporary relief due to the lack of early diagnosis and effective therapy, and thus the replacement of joints may be needed when the OA deteriorates. Although the intra-articular injection and oral administration of drugs are helpful for OA treatment, they are suffering from systemic toxicity, short retention time in joint, and insufficient bioavailability. Nanomedicine is potential to improve the drug delivery efficiency and targeting ability. In this focused progress review, the particle-based drug loading systems that can achieve targeted and triggered release are summarized. Stimuli-responsive nanocarriers that are sensitive to endogenous microenvironmental signals such as reactive oxygen species, enzymes, pH, and temperature, as well as external stimuli such as light for OA therapy are introduced in this review. Furthermore, the nanocarriers associated with targeted therapy and imaging for OA treatment are summarized. The potential applications of nanotherapies for OA treatment are finally discussed.