Recent advances of implantable systems and devices in cancer therapy and sensing

Malignant tumors have the capability to metastasize and colonize,meaning that they can spread to other organs and tissues,distributing metastatic focus and are hard to target.Although significant advances have been made in cancer treatment,it remains one of the leading causes of death around the globe.In recent years,new-emerging implantable systems and devices have been developed to tackle the challenge of metastatic tumors.In this review,implantable systems for suppressing tumors and preventing tumor recurrence are reported.In particular,we emphasize the responsive drug delivery systems and the external field assisted catalytic therapy for tumor treatment,as well as implantable biosensors for tumor microenvironment monitoring.We also conclude the open challenges and future perspectives of implantable systems and devices for cancer therapy and sensing.

Advances in Wireless,Batteryless,Implantable Electronics for Real‑Time,Continuous Physiological Monitoring

This review summarizes recent progress in developing wireless,batteryless,fully implantable biomedical devices for real-time continuous physiological signal monitoring,focusing on advancing human health care.Design considerations,such as biological constraints,energy sourcing,and wireless communication,are discussed in achieving the desired performance of the devices and enhanced interface with human tissues.In addition,we review the recent achievements in materials used for developing implantable systems,emphasizing their importance in achieving multi-functionalities,biocompatibility,and hemocompatibility.The wireless,batteryless devices offer minimally invasive device insertion to the body,enabling portable health monitoring and advanced disease diagnosis.Lastly,we summarize the most recent practical applications of advanced implantable devices for human health care,highlighting their potential for immediate commercialization and clinical uses.

Recent advances and innovations in the design and fabrication of wearable flexible biosensors and human health monitoring systems based on conjugated polymers

Wearable biosensors have received great interest as patient-friendly diagnostic technologies because of their high flexibility and conformability.The growing research and utilization of novel materials in designing wearable biosensors have accelerated the development of point-of-care sensing platforms and implantable biomedical devices in human health care.Among numerous potential materials,conjugated polymers(CPs)are emerging as ideal choices for constructing high-performance wearable biosensors because of their outstanding conductive and mechanical properties.Recently,CPs have been extensively incorporated into various wearable biosensors to monitor a range of target biomolecules.However,fabricating highly reliable CP-based wearable biosensors for practical applications remains a significant challenge,necessitating novel developmental strategies for enhancing the viability of such biosensors.Accordingly,this review aims to provide consolidated scientific evidence by summarizing and evaluating recent studies focused on designing and fabricating CP-based wearable biosensors,thereby facilitating future research.Emphasizing the superior properties and benefits of CPs,this review aims to clarify their potential applicability within this field.Furthermore,the fundamentals and main components of CP-based wearable biosensors and their sensing mechanisms are discussed in detail.The recent advancements in CP nanostructures and hybridizations for improved sensing performance,along with recent innovations in next-generation wearable biosensors are highlighted.CPbased wearable biosensors have been—and will continue to be—an ideal platform for developing effective and user-friendly diagnostic technologies for human health monitoring.

Implantable Electrochemical Microsensors for In Vivo Monitoring of Animal Physiological Information

In vivo monitoring of animal physiological information plays a crucial role in promptly alerting humans to potential diseases in animals and aiding in the exploration of mechanisms underlying human diseases.Currently,implantable electrochemical microsensors have emerged as a prominent area of research.These microsensors not only fulfill the technical requirements for monitoring animal physiological information but also offer an ideal platform for integration.They have been extensively studied for their ability to monitor animal physiological information in a minimally invasive manner,characterized by their bloodless,painless features,and exceptional performance.The development of implantable electrochemical microsensors for in vivo monitoring of animal physiological information has witnessed significant scientific and technological advancements through dedicated efforts.This review commenced with a comprehensive discussion of the construction of microsensors,including the materials utilized and the methods employed for fabrication.Following this,we proceeded to explore the various implantation technologies employed for electrochemical microsensors.In addition,a comprehensive overview was provided of the various applications of implantable electrochemical microsensors,specifically in the monitoring of diseases and the investigation of disease mechanisms.Lastly,a concise conclusion was conducted on the recent advancements and significant obstacles pertaining to the practical implementation of implantable electrochemical microsensors.

Deep brain implantable microelectrode arrays for detection and functional localization of the subthalamic nucleus in rats with Parkinson’s disease

The subthalamic nucleus(STN)is considered the best target for deep brain stimulation treatments of Parkinson’s disease(PD).It is difficult to localize the STN due to its small size and deep location.Multichannel microelectrode arrays(MEAs)can rapidly and precisely locate the STN,which is important for precise stimulation.In this paper,16-channel MEAs modified with multiwalled carbon nanotube/poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate)(MWCNT/PEDOT:PSS)nanocomposites were designed and fabricated,and the accurate and rapid identification of the STN in PD rats was performed using detection sites distributed at different brain depths.These results showed that nuclei in 6-hydroxydopamine hydrobromide(6-OHDA)-lesioned brains discharged more intensely than those in unlesioned brains.In addition,the MEA simultaneously acquired neural signals from both the STN and the upper or lower boundary nuclei of the STN.Moreover,higher values of spike firing rate,spike amplitude,local field potential(LFP)power,and beta oscillations were detected in the STN of the 6-OHDA-lesioned brain,and may therefore be biomarkers of STN localization.Compared with the STNs of unlesioned brains,the power spectral density of spikes and LFPs synchronously decreased in the delta band and increased in the beta band of 6-OHDA-lesioned brains.This may be a cause of sleep and motor disorders associated with PD.Overall,this work describes a new cellular-level localization and detection method and provides a tool for future studies of deep brain nuclei.

Clinical prediction of insufficient vaults after implantable collamer lens implantation

AIM:To determine the factors related to preoperative ocular characters that are predictive of insufficient vault(<250μm)after implantable collamer lens(ICL V4c;STAAR Surgical)implantation.METHODS:The participants underwent ICL surgery and were divided into the low(<250μm)and normal(250-1000μm)vault groups based on the postoperative vault at 3mo.The preoperative biometric parameters and clinical outcomes were compared between the two groups.The relationship between the 3-month vault values and preoperative ocular parameters were evaluated by Generalized estimating equations.RESULTS:Sixteen(23 eyes)and 36 patients(63 eyes)were in the low and normal vault groups,respectively.All implantation procedures were uneventful with no cataract formation in the early postoperative period.The sulcusto-sulcus lens rise(STSL)and iris ciliary angle(ICA)were correlated with vault at 3mo after surgery.Every 0.1 mm increase in STSL was associated with 38.9μm decrease in the postoperative 3-month vault.A rise of 1 degree in ICA is associated with a reduction of 4μm in vault.CONCLUSION:Eyes with a narrow ciliary sulcus are associated with a higher rate of low vault after ICL implantation,suggesting a need for adjustments to the ICL size in these patients.Evaluating the characteristics of the ciliary sulcus contributes valuable information to predict low vault after surgery.

Systemic modulation of skeletal mineralization by magnesium implant promoting fracture healing: Radiological exploration enhanced with PCA-based machine learning in a rat femoral model

The clinical application of magnesium(Mg)and its alloys for bone fractures has been well supported by in vitro and in vivo trials.However,there were studies indicating negative effects of high dose Mg intake and sustained local release of Mg ions on bone metabolism or repair,which should not be ignored when developing Mg-based implants.Thus,it remains necessary to assess the biological effects of Mg implants in animal models relevant to clinical treatment modalities.The primary purpose of this study was to validate the beneficial effects of intramedullary Mg implants on the healing outcome of femoral fractures in a modified rat model.In addition,the mineralization parameters at multiple anatomical sites were evaluated,to investigate their association with healing outcome and potential clinical applications.Compared to the control group without Mg implantation,postoperative imaging at week 12 demonstrated better healing outcomes in the Mg group,with more stable unions in 3D analysis and high-mineralized bridging in 2D evaluation.The bone tissue mineral density(TMD)was higher in the Mg group at the non-operated femur and lumbar vertebra,while no differences between groups were identified regarding the bone tissue volume(TV),TMD and bone mineral content(BMC)in humerus.In the surgical femur,the Mg group presented higher TMD,but lower TV and BMC in the distal metaphyseal region,as well as reduced BMC at the osteotomy site.Principal component analysis(PCA)-based machine learning revealed that by selecting clinically relevant parameters,radiological markers could be constructed for differentiation of healing outcomes,with better performance than 2D scoring.The study provides insights and preclinical evidence for the rational investigation of bioactive materials,the identification of potential adverse effects,and the promotion of diagnostic capabilities for fracture healing.

Rhegmatogenous retinal detachment in highly myopic eyes with implantable collamer lens

AIM:To investigate the clinical characteristics,treatment methods and outcomes of rhegmatogenous retinal detachment(RRD)in highly myopic eyes with implantable collamer lens(ICL).METHODS:High myopia patients who received treatment for nontraumatic RRD after ICL implantation surgery at the Retinal Department of Zhongshan Ophthalmic Center from Jan 2018 to Dec 2022 were reviewed.Comprehensive ophthalmologic examinations including visual acuity measurement and digital fundus photography were performed in each patient.RESULTS:A total of nine RRD eyes from nine patients who received V4c-ICL implantation were included.The mean time from ICL implantation surgery to the diagnosis of RRD was 32.44±22.56mo(range,1-60mo).At the initial visit for RRD,giant retinal tear(GRT),horseshoe tear,simple round hole,and horseshoe tear combined with round hole were detected in 3,3,2,and 1 eye(s),respectively,with maculaoff in eyes.Eight patients received surgical treatment,and one patient was treated by retinal laser photocoagulation alone.The ICL was preserved in 7 eyes.At the last followup,the mean best corrected visual acuity(BCVA)improved significantly from 1.76±1.06 logMAR at presentation to 0.81±1.01 logMAR(P=0.035),and no case of recurrent retinal detachment was found.CONCLUSION:The morphological presentation of retinal breaks is diverse in this study.The ICL can be preserved in most cases during the course of retinal detachment repair surgery in our data,companied with acceptable visual and anatomical outcomes.

New skin closure system facilitates wound healing after cardiovascular implantable electronic device surgery

The manuscript describes the efficacy of a new skin closure system(Zip Line?) for wound closure after pacemaker/implantable cardioverter defibrillator surgery. The system is particularly useful when wound healingis difficult with traditional methods and in patients at high risk for surgical site infections(SSIs). This skin closure option is easy and quick to apply and remove, and produces excellent cosmetic results. Although it is associated with a minimal expense upcharge, the benefits, including the potential for decrease in SSI, make it attractive and worth considering for skin closure in device patients, particularly those at increased risk of complications.

Wireless communication and wireless power transfer system for implantable medical device

Traditional magnetically coupled resonant wireless power transfer technology uses fixed distances between coils for research,to prevent fluctuations in the receiving voltage,and lead to reduce transmission efficiency.This paper proposes a closed-loop control wireless communication wireless power transfer system with a wearable four-coil structure to stabilize the receiving voltage fluctuation caused by changes in the displacement between the coils.Test results show that the system can provide stable receiving voltage,no matter how the distance between the transmitting coil and the receiving coil is changed.When the transmission distance is 20 mm,the power transfer efficiency of the system can reach 18.5%under the open-loop state,and the stimulus parameters such as the stimulation period and pulse width can be adjusted in real time through the personal computer terminal.

Postoperative efficacy,safety,predictability,and visual quality of implantable collamer lens implantation versus small incision lenticule extraction in myopic eyes:a Meta-analysis

AIM:To compare the postoperative efficacy,safety,predictability,and visual quality of implantable collamer lens(ICL)implantation versus small incision lenticule extraction(SMILE)in myopia eyes.METHODS:Pub Med,EMBASE,Web of Science,Cochrane Library and several Chinese databases were searched at May 2021 to select relevant studies in comparison of clinical outcomes between ICL implantation and SMILE for myopia.The primary outcomes were efficacy,safety,and predictability.And the secondary outcomes were postoperative higher-order ocular aberrations(HOAs),modulation transfer function cutoff frequency(MTF),objective scatter index(OSI),contrast sensitivity and a quality of vision(Qo V)questionnaire.RESULTS:A total of 1036 eyes from 10 studies,of which 503 eyes underwent ICL implantation and 533 eyes underwent SMILE,were enrolled in this Meta-analysis.Pooled results revealed that ICL group had a better safety index and post-corrected distance visual acuity(CDVA)(P=0.007,<0.00001,respectively),and a lower percentage of eyes with a postoperative CDVA lost 1 line(P=0.007)than the SMILE group.No significant differences were found in comparison of the other primary outcomes.In the longterm follow-up(>6mo),ICL group had a lower total HOA,coma,and spherical aberration than SMILE group(P=0.003,<0.00001,0.04).Yet higher trefoil was found in ICL group at 6mo after surgery(P=0.003).Additionally,ICL group also had a higher MTF value(P=0.02),and a higher contrast sensitivity score for spatial frequencies of 1.5,6,and 12 cpds(P=0.02,0.005,0.02,respectively).And it also had a lower score of bothersome in Qo V questionnaire than SMILE group(P=0.003).CONCLUSION:ICL implantation and SMILE have similar and comparable outcomes in term of the efficacy and predictability for correcting high myopia.However,ICL group is relatively safer and also has better visual quality in comparison of SMILE group.

Long-term observation on safety and visual quality of implantable collamer lens V4c implantation for myopia correction:a 5-year follow-up

AIM:To elucidate the safety and visual quality of implantable collamer lens with central hole(ICL V4c)implantation for correcting moderate and high myopia for at least 5y.METHODS:This retrospective study was conducted on 58 patients(114 eyes)who were followed up for at least 5y after ICL V4c implantation.The observation was done before and on 1d,1mo,1 and 5y or more after the surgical procedure.The visual acuity,subjective refraction,intraocular pressure,vault,axial length,central hole position,pupil diameter,visual quality,and adverse events were analyzed.The visual quality includes aberration,the modulation transfer function cutoff frequency(MTF cutoff),objective scattering index(OSI),Stroller's ratio(SR),and visual quality questionnaire.RESULTS:The average follow-up period was 69.25±3.80mo(range 60–82mo)and the preoperative spherical equivalent(SE)was-8.66±1.97 D.At 5y after operation,the safety index was 1.01±0.02 and the efficacy index was 0.99±0.42 and SE was-0.65±0.63 D.The 59.6%of the eyes achieved an uncorrected distance visual acuity of 20/20,76.3%of the eyes had SE within±1.0 D at the last visit.The axial length increased by 0.29±0.71 mm 5y after the surgery(t=-3.843,P<0.001).The mean vault at the last follow-up was 510.59±245.61μm.The central hole was on the temporal side in 80 eyes(84.2%).The visual quality questionnaire showed that 98.2%patients were satisfied with the surgical procedure.Adverse events occurred in 4 eyes(3.5%),including the posttraumatic toric ICL rotation(2 eyes),iris incarceration(1 eye),and posttraumatic ICL displacement(1 eye)at the last follow-up.CONCLUSION:Long-term ICL V4c implantation is safe,effective,and stable for correcting moderate and to high myopia,and the visual quality with patients is excellent and satisfactory,but the progression of axial length still needs attention after surgery.

Vault predicting after implantable collamer lens implantation using random forest network based on different features in ultrasound biomicroscopy images

AIM:To analyze ultrasound biomicroscopy(UBM)images using random forest network to find new features to make predictions about vault after implantable collamer lens(ICL)implantation.METHODS:A total of 450 UBM images were collected from the Lixiang Eye Hospital to provide the patient’s preoperative parameters as well as the vault of the ICL after implantation.The vault was set as the prediction target,and the input elements were mainly ciliary sulcus shape parameters,which included 6 angular parameters,2 area parameters,and 2 parameters,distance between ciliary sulci,and anterior chamber height.A random forest regression model was applied to predict the vault,with the number of base estimators(n_estimators)of 2000,the maximum tree depth(max_depth)of 17,the number of tree features(max_features)of Auto,and the random state(random_state)of 40.0.RESULTS:Among the parameters selected in this study,the distance between ciliary sulci had a greater importance proportion,reaching 52%before parameter optimization is performed,and other features had less influence,with an importance proportion of about 5%.The importance of the distance between the ciliary sulci increased to 53% after parameter optimization,and the importance of angle 3 and area 1 increased to 5% and 8%respectively,while the importance of the other parameters remained unchanged,and the distance between the ciliary sulci was considered the most important feature.Other features,although they accounted for a relatively small proportion,also had an impact on the vault prediction.After parameter optimization,the best prediction results were obtained,with a predicted mean value of 763.688μm and an actual mean value of 776.9304μm.The R²was 0.4456 and the root mean square error was 201.5166.CONCLUSION:A study based on UBM images using random forest network can be performed for prediction of the vault after ICL implantation and can provide some reference for ICL size selection.

Antitachycardia pacing programming in implantable cardioverter defibrillator:A systematic review

Implantable cardioverter defibrillator(ICD) programminginvolves several parameters. In recent years antitachycardia pacing(ATP) has gained an increasing importance in the treatment of ventricular arrhythmias, whether slow or fast. It reduces the number of unnecessary and inappropriate shocks and improves both patient's quality of life and device longevity. There is no clear indication regarding the type of ATP to be used, except for the treatment of fast ventricular tachycardias(188 bpm-250 bpm) where it has been shown a greater efficacy and safety of burst compared to ramp; 8 impulses in each sequence of ATP appears to be the best programming option in this setting. Beyond ATP use, excellent clinical results were obtained with programming standardization following these principles: extended detection time in ventricular fibrillation(VF) zone; supraventricular discrimination criteria up to 200 bpm; first shock in VF zone at the maximum energy in order to reduce the risk of multiple shocks. The MADIT-RIT trial and some observational registries have also recently demonstrated that programming with a widespread use of ATP, higher cut-off rates or delayed intervention reduces the number of inappropriate and unnecessary therapies and improves the survival of patients during mid-term follow-up.

A 16-channel high-voltage reconfigurable and flexible-controlled implantable wireless closed-loop system for SCI repair

An adaptive closed-loop system for spinal cord injury(SCI) repair is designed. It integrates stimulation and recording on 16 pairs of electrodes. Two switches(SAS3 T16/SAS1 T16 X2) fabricated in high-voltage 0.8 μm process with online re-configurable function are proposed. These two switches are combined with commercial off-the-shelf(COTS) electronics to implement the closed-loop implantable system in compact module. The system includes amplifier for recording neural signals, high-voltage stimulator, power transmission device, central processing module and flexible implantable electrodes. Two customized switches route any electrode to amplifier or stimulator, and nerve stimulation and signal recording are performed through lead wire-driven channels. The entire system is able to operate at up to 28 V, and is a biocompatible package with a volume of 42 mm×35 mm×8 mm. This system solves several problems encountered in implantable devices: low flexibility, negative influence of stimulus artifacts on neural detection and low integration of electrodes.

Implantable cardiac defibrillators in octogenarians

OBJECTIVE Implantable cardiac defibrillators(ICD)implantation in the very elderly remains controversial.We aimed to describe the experience and outcome of patients over 80 years old implanted with an ICD in Belgium.METHODS Data were extracted from the national QERMID-ICD registry.All implantations performed in octogenarians between February 2010 and March 2019 were analysed.Data on baseline patient characteristics,type of prevention,device configuration and all-cause mortality were available.To determine predictors of mortality,multivariable Cox proportional hazard regression modelling was performed.RESULTS Nationwide,704 primo ICD implantations were performed in octogenarians(median age 82,IQR 81-83 years;83% male and 45% secondary prevention).During a mean follow-up of 3.1±2.3 years,249(35%)patients died,of which 76(11%)within the first year after implantation.In multivariable Cox regression analysis age(HR=1.15,P=0.004),oncological history(HR=2.43,P=0.027)and secondary prevention(HR=2.23,P=0.001)were independently associated with 1-year mortality.A better preserved left ventricular ejection fraction(LVEF)was associated with a better outcome(HR=0.97,P=0.002).Regarding overall mortality multivariable analysis withheld age,history of atrial fibrillation,centre volume and oncological history as significant predictors.Higher LVEF was again protective(HR=0.99,P=0.008).CONCLUSIONS Primary ICD implantation in octogenarians is not often performed in Belgium.Among this population,11%died within the first year after ICD implantation.Advanced age,oncological history,secondary prevention and a lower LVEF were associated with an increased one-year mortality.Age,low LVEF,atrial fibrillation,centre volume and oncological history were indicative of higher overall mortality.

Spontaneous dislocation of a toric implantable collamer lens resulting in corneal endothelial decompensation:a case report and review of the literature

Dear Editor We present a case of spontaneous dislocation of a toric implantable collamer lens(TICL)resulting in corneal endothelial decompensation 8y after implantation.Since 2006,by helping people take off their glasses,the Visian TICL(Staar Surgical Co,Monrovia,CA,USA)have gained popularity in China.Though complications of intraocular pressure(IOP)elevation,cataract formation and endothelial damage exist as relevant problems,implantable collamer lens(ICL)implantation has been generally accepted as a viable option to correct moderate to high ametropia[1-2].

Expert consensus on the clinical application of totally implantable venous access devices in the upper arm(2022 Edition)

With the widespread adoption of ultrasound guidance,Seldinger puncture techniques,and intracardiac electrical positioning technology for the placement of peripherally inserted central catheters in recent years,an increasing number of medical staff and patients now accept peripheral placement of totally implantable venous access devices(TIVADs)in the upper arm.This approach has the advantage of completely avoiding the risks of hemothorax,pneumothorax,and neck and chest scarring.Medical specialties presently engaged in this study in China include internal medicine,surgery,anesthesiology,and interventional departments.However,command over implantation techniques,treatment of complications,and proper use and maintenance of TIVAD remain uneven among different medical units.Moreover,currently,there are no established quality control standards for implantation techniques or specifications for handling complications.Thus,this expert consensus is proposed to improve the success rate of TIVAD implantation via the upper-arm approach,reduce complication rates,and ensure patient safety.This consensus elaborates on the technical indications and contraindications,procedures and technical points,treatment of complications,and the use and maintenance of upper-arm TIVAD,thus providing a practical reference for medical staff.

Replace Implant System的临床应用及评价

目的 :评价ReplaceImplantSystem的临床效果。方法 :用ReplaceImplantSystem进行延期或即刻种植。采用埋入式二次手术方式 ,对72例患者植入90枚种植体 ,金属烤瓷冠修复 ,临床随访观察3年。结果 :种植体成功率100% ,种植体周齿槽骨水平吸收<0.2mm/年 ,烤瓷冠崩瓷4颗 ,固定螺丝钉松动1颗 ,种植体周围龈炎11颗。结论 :ReplaceImplantSystem适用于常见的牙列缺损的延期或即刻种植。

Gelatin-Based Metamaterial Hydrogel Films with High Conformality for Ultra-Soft Tissue Monitoring

Implantable hydrogel-based bioelectronics(IHB)can precisely monitor human health and diagnose diseases.However,achieving biodegradability,biocompatibility,and high conformality with soft tissues poses significant challenges for IHB.Gelatin is the most suitable candidate for IHB since it is a collagen hydrolysate and a substantial part of the extracellular matrix found naturally in most tissues.This study used 3D printing ultrafine fiber networks with metamaterial design to embed into ultra-low elastic modulus hydrogel to create a novel gelatin-based conductive film(GCF)with mechanical programmability.The regulation of GCF nearly covers soft tissue mechanics,an elastic modulus from 20 to 420 kPa,and a Poisson’s ratio from-0.25 to 0.52.The negative Poisson’s ratio promotes conformality with soft tissues to improve the efficiency of biological interfaces.The GCF can monitor heartbeat signals and respiratory rate by determining cardiac deformation due to its high conformability.Notably,the gelatin characteristics of the biodegradable GCF enable the sensor to monitor and support tissue restoration.The GCF metamaterial design offers a unique idea for bioelectronics to develop implantable sensors that integrate monitoring and tissue repair and a customized method for endowing implanted sensors to be highly conformal with soft tissues.