Reversible antibiotic loading and pH-responsive release from polymer brushes on contact lenses for therapy and prevention of corneal infections.

Corneal infection is an important cause of corneal damage and vision loss. In this work, polyhydroxy antibiotics were grafted onto polymer brush-modified contact lenses through dynamic chemical bonds between polyphenolic hydroxyls and phenylboronic acid. Both in vitro and in vivo antibacterial tests demonstrated great promise in the prevention of bacterial keratitis, which could be attributed to the enhanced retention time and drug bioavailability.

Author Correction: Repair of bone defects with prefabricated vascularized bone grafts and double-labeled bone marrow-derived mesenchymal stem cells in a rat model.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Clinical application of large channel endoscopic decompression in posterior cervical spine disorders.

BACKGROUND: We investigated the clinical value of posterior percutaneous endoscopic decompression (PED) for single-segment cervical spondylotic myelopathy (CSM) and cervical spondylotic radiculopathy (CSR). METHODS: Clinical data from February 2016 to March 2018 were collected for 32 patients with single-segment CSM or CSR who underwent posterior cervical percutaneous large channel endoscopic decompression and completed a regular follow-up exam at 12 months after surgery. Patient data included: age (range 30-81 years and mean of 49.5 years) and surgical information (operation time, bleeding volume, hospital stay, complications, etc.). The Japan Orthopedic Association (JOA) score and pain visual analog scale (VAS) were used to evaluate the surgical outcome for each patient. Cervical spine radiographs were used to evaluate cervical curvature (Cervical spondylotic angle (CSA), C2-7 Cobb angle) and CT and MRI were used to assess the extent of laminectomy and nerve root decompression. The JOA score, VAS score, cervical curvature were analyzed statistically, and the clinical outcome was evaluated using modified Macnab criteria at the last patient follow-up exam. RESULTS: The JOA and VAS scores were compared before and after surgery (1 day Pre-op; 3 days, 3 months and 12 months Post-op). The differences were statistically significant (P < 0.05). There were significant differences in cervical curvature (C2-7 Cobb angle) between the time points (1 day Pre-op; 3 days, 3 months and 12 months Post-op), but the differences were no statistically significant in CSA angle (P < 0.05) The operation time range was 45-110 min (mean 68.6 ± 23.8 min); the intraoperative blood loss range was 20-85 ml (mean28 ± 14.8 ml), and the hospital stay was 3-8 days (mean4.5 days). At the last follow-up, the clinical efficacy was evaluated using modified Macnab criteria. The results were excellent in 18 cases, good in 11 cases, and fair in 3 cases. The combined excellent and good rate was 93.75%. Postoperative CT and MRI showed that the compression of the spinal cord or nerve roots was completely relieved. CONCLUSION: Endoscopic decompression of posterior cervical vertebral disorders is a safe, effective, and minimally invasive surgical procedure with rapid recovery times. This procedure warrants additional research and clinical application.

Repair of bone defects with prefabricated vascularized bone grafts and double-labeled bone marrow-derived mesenchymal stem cells in a rat model.

This study aims to investigate the repair of bone defects with prefabricated vascularized bone grafts and double-labeled bone marrow-derived mesenchymal stem cells (BMSCs) in a rat model. BMSCs were separated from rat bone marrow. LTR-CMVpro-RFP and LTR-CMVpro-GFP were transfected into the BMSCs for in vitro and in vivo tracking. BMSCs-RFP and BMSCs-GFP were induced into endothelial progenitor cells (EPCs) and osteoblasts (OBs). Rats were divided into five groups: Group A: in vitro prefabrication with EPCs-RFP + in vivo prefabrication with arteriovenous vascular bundle + secondary OBs-GFP implantation; Group B: in vitro prefabrication with EPCs-RFP + secondary OBs-GFP implantation; Group C: in vivo prefabrication with arteriovenous vascular bundle + secondary OBs-GFP implantation; Group D: implantation of EPCs-RFP + implantation of with arteriovenous vascular bundle + simultaneous OBs-GFP implantation; Group E: demineralized bone matrix (DBM) grafts (blank control). Among five groups, Group A had the fastest bone regeneration and repair, and the regenerated bone highly resembled normal bone tissues; Group D also had fast bone repair, but the repair was slightly slower than Group A. Therefore, in vitro prefabrication with EPCs-RFP plus in vivo prefabrication with arteriovenous vascular bundle and secondary OBs-GFP implantation could be the best treatment for bone defect.

Episcleral drug film for better-targeted ocular drug delivery and controlled release using multilayered poly-ε-caprolactone (PCL).

UNLABELLED: Triamcinolone acetonide (TA) and poly-ε-caprolactone (PCL) were engineered into a micro drug film for episcleral application to better manage chronic vitreoretinal diseases such as proliferative vitreoretinopathy (PVR). Compared to an intravitreal drug injection, this drug film is much safer without breaking into ocular barriers. Compared to a traditional subtenon injection, this drug film demonstrated superior therapeutic duration, better drug bioavailability in the choroid and retina, and better-targeted drug delivery ability. The rabbit eye study demonstrated that using the PCL-TA film led to 5.6 and 3.4 times higher drug AUC in the choroid and the retina respectively than in eyes following a subtenon drug injection. The mean drug residence time in the rabbit choroid was also doubled by using the episcleral TA film (86days versus 43days). Remaining TA in the drug film was consistently higher than that in the subtenon space, indicating controlled release of TA by the PCL-TA film. The pharmacokinetics of triamcinolone in the choroid and retina were optimized from typical first-order kinetics to a more sustained release by use of this film. This episcleral film system worked better on rabbit eyes than on guinea pig eyes, indicating that scleral thickness and eye size may be crucial aspects to consider when choosing an animal model or when designing a transscleral delivery device for human use. This engineered drug film may be very useful in preventing and managing PVR associated with open globe trauma or surgical repair for retinal detachment. STATEMENT OF SIGNIFICANCE: This study demonstrated a novel micro episcleral drug film that is made from the engineering of triamcinolone acetonide (TA) into poly-ε-caprolactone (PCL). The film can be conveniently placed at the injury or disease site during primary surgery and provide controlled release of TA for four months that covers the high-risk time window for developing proliferative vitreoretinopathy (PVR). This engineered drug film may be very useful in preventing and managing PVR associated with open globe trauma or intraocular surgery.

[Application of tracing technique of labeling bone marrow mesenchymal stem cells with green fluorescent protein in tissue-engineered bone construction in vitro].

This study was designed to label rat bone marrow mesenchymal stem cells (rBMSCs) with humanized renillar green fluorescent protein (hrGFP) for exploring the detectable effects of hrGFP on the construction of tissue-engineered bone in vitro. The hrGFP expression plasmid was packed into lentivirus by 293FT cells and transduced into rat BMSCs. After transduction, 81.3% rBMSCs successfully expressed green fluorescence. The hrGFP-rBMSCs were statically loaded on Bioglass-Collagen-Hyaluronic Acid-Phosphatidylserine (BG-COL-HYA-PS) scaffold in complete L-DMEM medium or osteogenic medium for 14 days. At 6h, a number of cells expressing green fluorescence can be observed by fluorescent microscopy. At day 7 and 14 after co-culture, the number of cells on the scaffold gradually increased. After 14 days for osteogenic induction, the hrGFP-rBMSCs and the interior of scaffold can be detected the expression of type I collagen. The results demonstrate that hrGFP labelling technique can detect visualizedly and effectively cell adhesion, proliferation and osteogenic differentiation in the construction of tissue-engineered bone in vitro.

Biocompatibility and osteogenesis of biomimetic Bioglass-Collagen-Phosphatidylserine composite scaffolds for bone tissue engineering.

A novel biomimetic composite scaffold Bioglass-Collagen-Phosphatidylserine (BG-COL-PS) was fabricated with a freeze-drying technique. The macrostructure and morphology as well as mechanical strength of the scaffolds were characterized. Scanning electronic microscopy (SEM) showed that the BG-COL-PS scaffolds exhibited interconnected porous structures with pore sizes of several microns up to about 300 µm. The scaffolds have a porosity of 75.40% and the corresponding compressive strength of 1.5469 Mpa. Rat mesenchymal stem cells (rMSCs) were seeded on BG-COL-PS or BG-COL scaffolds and cultured for 21 days in vitro. Based on the results of SEM, dsDNA content, alkaline phosphatase (ALP) activity, osteogenic gene expression analysis and alizarin red staining, the responses of MSCs to the scaffold exhibited a higher degree of attachment, growth as well as osteogenic differentiation than those on BG-COL scaffolds in vitro. To investigate the in vivo biocompatibility and osteogenesis of the composite scaffolds, both pure BG-COL-PS scaffolds and MSC/scaffold constructs were implanted in rat femurs defects for 6 weeks and studied histologically and radiographically. The in vivo results showed that BG-COL-PS composite scaffolds exhibited good biocompatibility and extensive osteoconductivity with host bone. Moreover, the BG-COL-PS/MSC constructs dramatically enhanced the efficiency of new bone formation than pure BG-COL-PS scaffolds or BG-COL/MSC constructs. All these results demonstrate the usefulness of PS composited BG-COL-PS scaffolds for inducing enhanced bone formation. The BG-COL-PS scaffolds fulfill the basic requirements of bone tissue engineering scaffold and have the potential to be applied in orthopedic and reconstructive surgery.

A novel biomimetic composite scaffold hybridized with mesenchymal stem cells in repair of rat bone defects models.

In this study, the in vivo bone-regenerative potential of a novel bioactive glass-collagen-hyaluronic acid-Phosphatidylserine (BG-COL-HYA-PS) composite scaffold hybridized with mesenchymal stem cells (MSCs) was investigated in a rat bone defect model. HrGFP-labeled MSCs were cultured for 2 weeks on the BG-COL-HYA-PS scaffold before implantation into the defect. A cell-free scaffold and an untreated defect were used as controls. The regeneration process was evaluated by histology, X-ray, and mechanical rigidity experiments at different time points post-implantation. The results revealed that BG-COL-HYA-PS scaffold exhibited a low inflammatory response and foreign body response within 3 weeks. At week 6, those responses disappeared following the resorption of scaffolds and the formation of new bone. Compared with the pure scaffold or empty group, the introduction of MSCs into the porous scaffold dramatically enhanced the efficiency of the new bone formation and biomechanical property of the femur. In addition, the transplanted MSCs could survive for up to 3 weeks or longer. The results demonstrated that the BG-COL-HYA-PS scaffold was biocompatible and osteoconductive and the transplanted MSCs with the scaffold enhanced the healing of the bone defect.