Tendon Repair and Regeneration Using Bioinspired Fibrillation Engineering That Mimicked the Structure and Mechanics of Natural Tissue.

Replicating the controlled nanofibrillar architecture of collagenous tissue represents a promising approach in the design of tendon replacements that have tissue-mimicking biomechanics─outstanding mechanical strength and toughness, defect tolerance, and fatigue and fracture resistance. Guided by this principle, a fibrous artificial tendon (FAT) was constructed in the present study using an engineering strategy inspired by the fibrillation of a naturally spun silk protein. This bioinspired FAT featured a highly ordered molecular and nanofibrillar architecture similar to that of soft collagenous tissue, which exhibited the mechanical and fracture characteristics of tendons. Such similarities provided the motivation to investigate FAT for applications in Achilles tendon defect repair. In vitro cellular morphology and expression of tendon-related genes in cell culture and in vivo modeling of tendon injury clearly revealed that the highly oriented nanofibrils in the FAT substantially promoted the expression of tendon-related genes combined with the Achilles tendon structure and function. These results provide confidence about the potential clinical applications of the FAT.

Precise manipulation of circadian clock using MnO2 nanocapsules to amplify photodynamic therapy for osteosarcoma.

Circadian rhythm (CR) disruption contributes to tumor initiation and progression, however the pharmacological targeting of circadian regulators reversely inhibits tumor growth. Precisely controlling CR in tumor cells is urgently required to investigate the exact role of CR interruption in tumor therapy. Herein, based on KL001, a small molecule that specifically interacts with the clock gene cryptochrome (CRY) functioning at disruption of CR, we fabricated a hollow MnO2 nanocapsule carrying KL001 and photosensitizer BODIPY with the modification of alendronate (ALD) on the surface (H-MnSiO/K&B-ALD) for osteosarcoma (OS) targeting. The H-MnSiO/K&B-ALD nanoparticles reduced the CR amplitude in OS cells without affecting cell proliferation. Furthermore, nanoparticles-controlled oxygen consumption by inhibiting mitochondrial respiration via CR disruption, thus partially overcoming the hypoxia limitation for photodynamic therapy (PDT) and significantly promoting PDT efficacy. An orthotopic OS model demonstrated that KL001 significantly enhanced the inhibitory effect of H-MnSiO/K&B-ALD nanoparticles on tumor growth after laser irradiation. CR disruption and oxygen level enhancement induced by H-MnSiO/K&B-ALD nanoparticles under laser irradiation were also confirmed in vivo. This discovery first demonstrated the potential of CR controlling for tumor PDT ablation and provided a promising strategy for overcoming tumor hypoxia.

Treatment of 2-Part Proximal Humeral Fractures in Osteoporotic Patients With Medial Calcar Instability Using a PHILOS Plate Plus an Allogeneic Fibula Inserted Obliquely - A Retrospective Study.

INTRODUCTION: To date, there is little research assessing the efficacy of a proximal humeral internal locking system (PHILOS) plate plus an allogeneic fibula inserted obliquely in the treatment of 2-part proximal humerus fractures (PHFs) with calcar comminution in patients >60 years old with severe osteoporosis. The aim of this study was to retrospectively evaluate the outcomes of elderly patients with osteoporotic 2-part PHFs combined with medial column (calcar) instability or disruption who experienced a PHILOS plate plus an allogeneic fibula inserted obliquely. MATERIALS AND METHODS: One hundred and twelve consecutive elderly patients with severe osteoporotic 2-part PHFs combined with calcar instability or disruption who were treated with a PHILOS plate plus an allogeneic fibula inserted obliquely were retrospectively identified from 3 tertiary medical centres during 2014-2019. The primary outcomes were the Constant scores and American Shoulder and Elbow Surgeons (ASES) scores; secondary outcome was the rate of key orthopaedic complications. RESULTS: Median follow-up was 24 (15.3-27.6) months. Significant improvements in the median Constant scores were observed (39 [26-58 points] prior to surgery vs 81 [67-95 points] at final follow-up). The median ASES scores improved from 43 (26-64 points) prior to surgery to 83 (65-96 points) at final follow-up. The percentage of key orthopaedic complications was 25.6% (22/86). Four (4.7%) cases had loss of reduction, 4 (4.7%) experienced aseptic loosening, 1 (.8%) had non-union, 4 (4.7%) suffered a periprosthetic fracture, 3 (3.5%) experienced a revision surgery, 1 (.8%) had a dislocation and 5 (5.8%) suffered an unbearable shoulder pain. CONCLUSION: For elderly patients with osteoporotic 2-part PHFs combined with calcar instability or disruption, PHILOS plate combined with an allogeneic fibula inserted obliquely might have recognisable advantages in decreasing the loss of fixation and preventing medial calcar collapse.

Initiation of Targeted Nanodrug Delivery in Vivo by a Multifunctional Magnetic Implant.

Implant-mediated targeted drug delivery without an external magnetic field is very challenging. In this work, we report targeted nanodrug delivery initiated by a Fe3O4/poly(lactic-co-glycolic acid) implant scaffold with high magnetism. The implant scaffold is biocompatible and durable. It effectively attracts nanodrugs to its surface, thus killing cancer cells. These findings provide a proof of concept for the magnetic implant-directed nanodrug targeting without the need for an external magnetic field. This approach may further facilitate more precise medical treatments.

Dual-responsive colloidal microcapsules based on host-guest interaction on solid templates.

Colloidal microcapsules (MCs) have received considerable attention in the fields of microencapsulation, drug delivery as well as microreactors due to their unique nanoparticles-composed structure. In this study, dual-responsive colloidal MCs based on host-guest interaction were successfully fabricated via a layer-by-layer assembly method on sacrificial solid templates. Ferrocene-modified polyethylenimine (PEI-Fc) and cyclodextrin-modified polystyrene nanoparticles (PS-CD NPs) were used as building blocks for assembly. The colloidal MCs could be disassembled into nano-components upon addition of competitive adamantane (Ad) molecules or in the solution with a pH lower than 4.