Smart Hydrogels for Bone Reconstruction via Modulating the Microenvironment

Rapid and effective repair of injured or diseased bone defects remains a major challenge due to shortages of implants. Smart hydrogels that respond to internal and external stimuli to achieve therapeutic actions in a spatially and temporally controlled manner have recently attracted much attention for bone therapy and regeneration. These hydrogels can be modified by introducing responsive moieties or embedding nanoparticles to increase their capacity for bone repair. Under specific stimuli, smart hydrogels can achieve variable, programmable, and controllable changes on demand to modulate the microenvironment for promoting bone healing. In this review, we highlight the advantages of smart hydrogels and summarize their materials, gelation methods, and properties. Then, we overview the recent advances in developing hydrogels that respond to biochemical signals, electromagnetic energy, and physical stimuli, including single, dual, and multiple types of stimuli, to enable physiological and pathological bone repair by modulating the microenvironment. Then, we discuss the current challenges and future perspectives regarding the clinical translation of smart hydrogels

Bone/cartilage organoid on-chip: Construction strategy and application

The necessity of disease models for bone/cartilage related disorders is well-recognized, but the barrier between ex-vivo cell culture, animal models and the real human body has been pending for decades. The organoid-on-a-chip technique showed opportunity to revolutionize basic research and drug screening for diseases like osteoporosis and arthritis. The bone/cartilage organoid on-chip (BCoC) system is a novel platform of multi-tissue which faithfully emulate the essential elements, biologic functions and pathophysiological response under real circumstances. In this review, we propose the concept of BCoC platform, summarize the basic modules and current efforts to orchestrate them on a single microfluidic system. Current disease models, unsolved problems and future challenging are also discussed, the aim should be a deeper understanding of diseases, and ultimate realization of generic ex-vivo tools for further therapeutic strategies of pathological conditions

M2 macrophage-derived exosomes promote diabetic fracture healing by acting as an immunomodulator

Diabetes mellitus is a chronically inflamed disease that predisposes to delayed fracture healing. Macrophages play a key role in the process of fracture healing by undergoing polarization into either M1 or M2 subtypes, which respectively exhibit pro-inflammatory or anti-inflammatory functions. Therefore, modulation of macrophage polarization to the M2 subtype is beneficial for fracture healing. Exosomes perform an important role in improving the osteoimmune microenvironment due to their extremely low immunogenicity and high bioactivity. In this study, we extracted the M2-exosomes and used them to intervene the bone repair in diabetic fractures. The results showed that M2-exosomes significantly modulate the osteoimmune microenvironment by decreasing the proportion of M1 macrophages, thereby accelerating diabetic fracture healing. We further confirmed that M2-exosomes induced the conversion of M1 macrophages into M2 macrophages by stimulating the PI3K/AKT pathway. Our study offers a fresh perspective and a potential therapeutic approach for M2-exosomes to improve diabetic fracture healing

Responses of Phospholipase D and Antioxidant System to Mechanical Wounding in Postharvest Banana Fruits

Banana fruits are susceptible to mechanical damage. The present study was to investigate the responses of phospholipase D (PLD) and antioxidant system to mechanical wounding in postharvest banana fruits. During 16 d storage at 25°C and 90% relative humidity, PLD activity in wounded fruits was significantly higher than that in control (without artificial wounding fruits). The higher value of PLD mRNA was found in wounded fruits than in control. PLD mRNA expression reached the highest peak on day 4 in both groups, but it was 2.67 times in wounded fruits compared to control at that time, indicating that PLD gene expression was activated in response to wounding stress. In response to wounding stress, the higher lipoxygenase (LOX) activity was observed and malondialdehyde (MDA) production was accelerated. The activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX) in wounded fruits were significantly higher than those in control. The concentrations of reactive oxygen species (ROS) such as superoxide anion (O2•-) and hydrogen peroxide (H2O2) in fruits increased under mechanical wounding. The above results provided a basis for further investigating the mechanism of postharvest banana fruits adapting to environmental stress

Influence of polysaccharide-based edible coatings on enzymatic browning and oxidative senescence of fresh-cut lettuce

Fresh-cut lettuce has a short shelf-life due to enzymatic browning and oxidative senescence. The present study investigated effects of polysaccharide-based edible coatings (alginate, chitosan, and carrageenan) on enzymatic browning and antioxidant defense system of fresh-cut lettuces during cold storage (4°C) for 15 days. The results showed that three coatings could inhibit enzymatic browning through maintaining total phenolics (TP) content and decreasing polyphenol oxidase (PPO) and phenylalanine ammonialyase (PAL) activities. These coatings also reduced phospholipase D (PLD) and lipoxygenase (LOX) activities, lowered malondialdehyde (MDA) content, and enhanced antioxidant enzymes (superoxide dismutase, SOD; peroxidase, POD; catalase, CAT; ascorbate peroxidase, APX) activities. Besides, all coatings positively affected sensory properties of fresh-cut lettuces after 3 days storage. Additionally, among three coating treatments, chitosan coating had the most positive effects on quality of fresh-cut lettuce and was the most suitable coating for retarding enzymatic browning and alleviating membrane oxidative damage. These results indicated that polysaccharide-based edible coatings were helpful to maintain quality, inhibit enzymatic browning, and postpone senescence of fresh-cut lettuce

Bilateral C1 laminar hooks combined with C2 pedicle screws fixation for treatment of C1–C2 instability not suitable for placement of transarticular screws

The study design described here is a posterior C1–C2 fusion technique composed of bilateral C1 hooks and C2 pedicle screws. In addition, the clinical results of using this method on 13 patients with C1–C2 instability are reported. The objectives are to introduce a new technique for posterior C1–C2 fusion and to evaluate the clinical outcome of using it to treat C1–C2 instability. From October 2006 to August 2008, 13 patients (9 men and 4 women) with C1–C2 instability were included in this study: 3 had acute odontoid fractures, 4 had obsolete odontoid fractures, 4 had os odontoideum and 2 had traumatic rupture of the transverse ligament. All patients underwent posterior atlantoaxial fixation with bilateral C1 hooks and C2 pedicle screws. The mean follow-up duration was 25 months (range 13–30 months). Each patient underwent a complete cervical radiograph series, including anterior–posterior, lateral, and flexion–extension views, and a computed tomographic scan. The clinical course was evaluated according to the Frankel grading system. No clinically manifested injury of the nerve structures or the vertebral artery was observed in any of these cases. Five patients with neurological symptoms showed significant improvement in neurological function postoperatively. Bony fusion and construction stability were observed in all 13 patients (100%) on their follow-up radiographs, and no instrument failure was observed. Bilateral C1 hooks combined with C2 pedicle screws can be used as an alternative treatment method for C1–C2 dislocation, especially in cases not suitable for the use of transarticular screws. The clinical follow-up shows that this technique is a safe and effective method of treatment