ObjectiveTo observe the safety of 2-port non-vitrectomized subretinal injection (SRI) for the treatment of Bietti crystalline dystrophy (BCD). MethodsA exploratory clinical study. From February to May 2023, 6 BCD patients with 6 eyes who were confirmed by examination in Xiamen Eye Center of Xiamen University and were treated with SRI adeno-associated virus vector transgenic drugs were included in the study. Among them, 2 males had 2 eyes and 4 females had 4 eyes. Age were 34-60 years old. The study eye underwent adeno associated virus gene therapy via 2-port non-vitrectomized SRI. Two scleral ports were created using 25G vitrectomy trocar to place the light pipe and injection cannula. Anterior chamber paracentesis was performed to lower intraocular pressure. Under the silicone oil infusion mode of the vitrectomy machine, a 38G injection cannula penetrated the retina to reach the subretinal space. The injection speed was controlled by the foot pedal of the vitrectomy machine, and the drug was slowly injected into the subretinal space to create a subretinal bleb. if intra-ocular pressure assessed by finger palpation was high at the end of injection, drainage of the aqueous humor can be made by compressing the cornea incision until the intraocular pressure was normal. Patients were followed for 9-12 months and be examined using the same equipment and methods as before. ResultsRetinal pigment epithelium and choroidal atrophy were observed in all 6 eyes of 6 patients were graded as stage Ⅲ by the fundus examination revealing atrophy of retinal pigmented epithelium and choroid, with or without yellow-white crystals and/or complex lipid. The range were operation time 9-14 minutes. No vitreous prolapse, retinal hemorrhage, or retinal tear was observed during surgery. After 24 hours, optical coherence tomogrophy examination showed absorption of subretinal fluid and retinal reattachment. None of the six patients showed corneal keratic precipitates, anterior chamber cells, vitreous cells, inflammation, high intraocular pressure, or retinal tear within the 9-month follow-up. ConclusionSubretinal injection without vitrectomy using two ports is a safe and feasible alternative for adult gene therapy, and it shortens the surgical time.
Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes, which seriously threatens the vision of patients. The pathogenesis of DR Is complex and involves many pathophysiological processes. At present, the treatment methods for DR Mainly include panretinal laser photocoagulation, vitrectomy and vitreous cavity injection, etc. However, each treatment method has certain limitations. In recent years, remarkable progress has been made in the field of drug treatment of DR, especially in anti-vascular endothelial growth factor drugs, anti-inflammatory drugs, anti-oxidative stress damage drugs, neuroprotective agents, gene therapy and stem cell therapy. These drugs not only improve the effectiveness of treatment, but also expand the range of treatment options. In addition, by carrying DR Treatment drugs on carriers such as nanoparticles, hydrogels and photosensitive materials, continuous and efficient release of drugs in the eye is achieved, thereby extending the time interval of administration and reducing the need for frequent treatment of patients. In the future, based on biomarker detection technology, it is expected to promote the development of personalized and precise treatment, which can develop more accurate treatment plans for patients and improve the efficacy.
In existing vascular interventional surgical robots, it is difficult to accurately detect the delivery force of the catheter/guidewire at the slave side. Aiming to solve this problem, a real-time force detection system was designed for vascular interventional surgical (VIS) robots based on catheter push force. Firstly, the transfer process of catheter operating forces in the slave end of the interventional robot was analyzed and modeled, and the design principle of the catheter operating force detection system was obtained. Secondly, based on the principle of stress and strain, a torque sensor was designed and integrated into the internal transmission shaft of the slave end of the interventional robot, and a data acquisition and processing system was established. Thirdly, an ATI high-precision torque sensor was used to build the experimental platform, and the designed sensor was tested and calibrated. Finally, sensor test experiments under ideal static/dynamic conditions and simulated catheter delivery tests based on actual human computed tomography (CT) data and vascular model were carried out. The results showed that the average relative detection error of the designed sensor system was 1.26% under ideal static conditions and 1.38% under ideal dynamic stability conditions. The system can detect on-line catheter operation force at high precision, which is of great significance towards improving patient safety in interventional robotic surgery.
Objective To explore the mechanism of antibiotic delivery system targeting bacterial biofilm with linezolid (LZD) based on ε-poly-L-lysine (ε-PLL) and cyclodextrin (CD) (ε-PLL-CD-LZD), aiming to enhance antibiotic bioavailability, effectively penetrate and disrupt biofilm structures, and thereby improve the treatment of bone and joint infections. Methods ε-PLL-CD-LZD was synthesized via chemical methods. The grafting rate of CD was characterized using nuclear magnetic resonance. In vitro biocompatibility was evaluated through live/dead cell staining after co-culturing with mouse embryonic osteoblast precursor cells (MC3T3-E1), human umbilical vein endothelial cells, and mouse embryonic fibroblast cells (3T3-L1). The biofilm-enrichment capacity of ε-PLL-CD-LZD was assessed using Staphylococcus aureus biofilms through enrichment studies. Its biofilm eradication efficacy was investigated via minimum inhibitory concentration (MIC) determination, scanning electron microscopy, and live/dead bacterial staining. A bone and joint infection model in male Sprague-Dawley rats was established to validate the antibacterial effects of ε-PLL-CD-LZD. Results In ε-PLL-CD-LZD, the average grafting rate of CD reached 9.88%. The cell viability exceeded 90% after co-culturing with three types cells. The strong biofilm enrichment capability was observed with a MIC of 2 mg/L. Scanning electron microscopy observations revealed the effective disruption of biofilm structure, indicating potent biofilm eradication capacity. In vivo rat experiments demonstrated that ε-PLL-CD-LZD significantly reduced bacterial load and infection positivity rate at the lesion site (P<0.05). ConclusionThe ε-PLL-CD antibiotic delivery system provides a treatment strategy for bone and joint infections with high clinical translational significance. By effectively enhancing antibiotic bioavailability, penetrating, and disrupting biofilms, it demonstrated significant anti-infection effects in animal models.
ObjectiveTo review the research progress of intra-articular targeted delivery of nanomaterials in the treatment of osteoarthritis (OA). MethodsThe domestic and foreign related literature on intra-articular targeted delivery of nanomaterials for the treatment of OA was extensively reviewed, and their targeting strategies were discussed and summarized. Results Rapid drug clearance from the joint remains a critical limitation in drug efficacy. Nanocarriers can not only significantly improve the residence profiles of drugs in the joint, but also achieve targeted delivery of drugs to specific joint tissues through active or passive targeting strategies. Conclusion With the continuous development of various emerging tissue- or cell-specific drugs, the targeted delivery of drugs with nanomaterials promise to realize the clinical translation of these drugs in the treatment of OA.
Hydrogel is a creative polymeric biomaterial which can resemble extracellular matrix (ECM) in vitro. Hydrogel is also a material with intrinsic bioinert, but it can offer mechanical support and developmental guide for cell growth and new tissue organization by designing physicochemical and biological properties of hydrogels precisely. This review mainly introduces design of hydrogels, properties and applications in tissue engineering and regenerative medicine, drug delivery, stem cell culture and cell therapy.
Gene therapy is designed to introduce genetic material into the cells of a patient via virus to enhance, inhibit, edit or add a genetic sequence, results in a therapeutic or prophylactic effect. Gene therapy has brought positive influence and great potential for the treatment of retinal diseases including genetic retinal diseases and acquired retinal diseases. In addition to the constant optimization of gene vectors, the exploration of different drug delivery techniques has brought different therapeutic effects for gene therapy of retinal diseases. The main delivery methods include subretinal injection, intravitreal injection, suprachoroidal injection. Considering the transfection efficiency and safety of delivery methods, emerging sub-inner limiting membrane injection and noninvasive gene delivery are under investigation. The selection of gene delivery method is very important for the safety and effectiveness of gene therapy for retinal diseases. It is not only related to the development of equipment and technology, but also related to the modification of adeno-associated virus, the selection of promoter and the specific retinal cells that the target gene wants to be transfected. Therefore, the most appropriate method of gene delivery should be selected according to the final gene therapy agent and the specific transfected cells after taking all these factors into consideration.
Microneedles have emerged as the new class of local drug delivery system that has broad potential for development. Considering that the microneedles can penetrate tissue barriers quickly, and provide localized and targeted drug delivery, their applications have gradually expanded to non-transdermal drug delivery recently, which are capable of providing rapid and effective treatment for injuries and diseases of organs or tissues. However, a literature search revealed that there is a lack of summaries of the latest developments in non-transdermal drug delivery research by using biomedical polymeric microneedles. The review first described the materials and fabrication methods for the polymeric microneedles, and then reviewed a representative application of microneedles for non-transdermal drug delivery, with the primary focus being on treating and repairing the tissues or organs such as oral cavity, ocular tissues, blood vessels and heart. At the end of the article, the opportunities and challenges associated with microneedles for non-transdermal drug delivery were discussed, along with its future development, in order to provide reference for researchers in the relevant field.
ObjectiveTo summarize the research progress of tissue engineering technology to promote bone tissue revascularization in osteonecrosis of the femoral head (ONFH).MethodsThe relevant domestic and foreign literature in recent years was extensively reviewed. The mechanism of femoral head vascularization and the application progress of tissue engineering technology in the promotion of ONFH bone tissue revascularization were summarized.ResultsRebuilding or improving the blood supply of the femoral head is the key to the treatment of ONFH. Tissue engineering is a hot spot in current research. It mainly focuses on the three elements of seed cells, scaffold materials, and angiogenic growth factors, combined with three-dimensional printing technology and drug delivery systems to promote the revascularization of the femoral bone tissue.ConclusionThe strategy of revascularization of the femoral head can improve the local blood supply and delay or even reverse the progression of ONFH disease.
The treatment of hereditary retinopathy depends on gene replacement or editing therapy, and adeno-associated virus (AAV) vector is one of the most widely used gene transfer vectors. The delivery methods of AAV vector-mediated target genes to the retina inlucde intravitreal injection, subretinal injection, and suprachorioidal injection. Intravitreal injection of AAV vector is currently the most commonly used delivery route, which can effectively improve the functions of retina disorders such as blinding retinal dystrophy in mice. Subretinal injection of AAV vector can deliver the target gene to the local retina, resulting in stronger efficiency of transfection and gene expressio, however, the high technical operations are required. In recent years, as a new high-profile delivery route suprachorioidal injection of AAV vector can achieve more extensive transfection of target genes in the retina of rabbits and rats. At present, the efficiency of AAV vector transduction in the retina is affected by the delivery mode. In the future, it is necessary to further explore the effect of AAV vector delivery mode on the transduction efficiency in order to find an important delivery route for mediating gene therapy for retinal diseases.