In recent years,China has made great progress in basic nanomedicine,nanotoxicology and nanobiology research.Nanotechnology has been continuously applied in biomaterial and medical device,more and more medical devices applying nanomaterials are developed and manufactured.In order to gain more comprehension and accurate understanding of the research and industrial development in nanobiomaterial medical devices,this study reviewed the common nanomaterial in medical devices and the regulatory situation of nanomaterial medical devices at home and abroad,and discussed the current challenges in biological evaluation of nanomaterial medical devices,with a view to providing ideas for the safety evaluation and research of related products.

Sympathetic cues via the adrenergic signaling critically regulate bone homeostasis and contribute to neurostress-induced bone loss, but the mechanisms and therapeutics remain incompletely elucidated. Here, we reveal an osteoclastogenesis-centered functionally important osteopenic pathogenesis under sympatho-adrenergic activation with characterized microRNA response and efficient therapeutics. We discovered that osteoclastic miR-21 was tightly regulated by sympatho-adrenergic cues downstream the β2-adrenergic receptor (β₂AR) signaling, critically modulated osteoclastogenesis in vivo by inhibiting programmed cell death 4 (Pdcd4), and mediated detrimental effects of both isoproterenol (ISO) and chronic variable stress (CVS) on bone. Intriguingly, without affecting osteoblastic bone formation, bone protection against ISO and CVS was sufficiently achieved by a (D-Asp₈)-lipid nanoparticle-mediated targeted inhibition of osteoclastic miR-21 or by clinically relevant drugs to suppress osteoclastogenesis. Collectively, these results unravel a previously underdetermined molecular and functional paradigm that osteoclastogenesis crucially contributes to sympatho-adrenergic regulation of bone and establish multiple targeted therapeutic strategies to counteract osteopenias under stresses.
Adrenergic Agents/pharmacology* ; Apoptosis Regulatory Proteins/pharmacology* ; Bone Diseases, Metabolic/metabolism* ; Humans ; Liposomes ; MicroRNAs/genetics* ; Nanoparticles ; Osteoclasts ; Osteogenesis/physiology* ; RNA-Binding Proteins/pharmacology*

To broadly understand the new direction of biological evaluation for medical devices, we introduced both domestic and international progress of biological evaluation and focused on illustrating the key points on full life-cycle biological evaluation, toxicological risk evaluation, evaluation endpoints and package material evaluation concern as well as how to use the update vision of ISO 10993-1:2018 scientifically and reasonably in order to provide us better services on performing biological evaluation for medical devices.
Equipment and Supplies

Objective:The study aimed to evaluate the effect of systemic-pulmonary shunt(SPS) on the infants with tetralogy of Fallot(TOF) with hypoplasia pulmonary arteries.Methods:Among 949 infants less than three-year-old who underwent surgical intervention between January 2010 and December 2015, 853 infants underwent one-stage primary repair(group Ⅰ), whereas 96 infants underwent SPS(group Ⅱ). Among them, 546 were males and 403 were females. The average age and average weight at operation were 13 months and 9.4 kg, respectively. 20.8% infants had clinical symptoms before operation. Perioperative and follow-up parameters were assessed including age, weight, sex, transcutaneous oxygen saturation(SPO 2), preoperative clinic symptom, ratio of McGoon, NAKATA index, Z score of pulmonary annulus, left ventricular end diastolic diameter(LVEDD). Results:There were 28(3.0%) early postoperative deaths in the whole group. And no significant difference in mortality was found between group Ⅰ(2.9%) and group Ⅱ(3.1%). Compared with group Ⅰ, age and weight were significantly lower in patients in group Ⅱ[(0.95±0.56)years old vs.(1.09±0.59)years old] and[(8.6±1.8)kg vs.(9.5±2.1)kg], respectively. Patients in group Ⅱ had a lower SPO 2(0.75±0.09 vs. 0.85±0.09) and was more prone to appear hypoxic spell(30.2% vs. 19.7%) than patients in group Ⅰ. Patients in group Ⅱ had a more poor development in pulmonary artery. The ratio of McGoon, NAKATA index and Z score of pulmonary annulus in group Ⅱ were significantly less than that in group Ⅰ[1.4±0.3 vs. 1.9±0.5, (124±43)mm 2/m 2 vs.(222±88)mm 2/m 2 and-4.3±2.6 vs.-2.3±2.1], respectively. There was no difference of extubation time bewteen two groups. SPO 2 rose significantly from 0.75 to 0.83 after SPS. And after SPS, the diameter of main pulmonary artery, the ratio of McGoon, NAKATA index and Z score of pulmonary annulus increased significantly from 6.4 mm, 1.42, 126.4 mm 2/m 2 and -4.3 to 9.2 mm, 1.83, 212.6 mm 2/m 2 and -2.4, respectively. Moreover, LVEDD also increased significantly from 21.2 mm to 24.5 mm after SPS. Conclusion:SPS is safe and effective for little infants with anoxic spell and hypoplasia pulmonary arteries. SPS can improve oxygenation significantly and delay the age for radical surgery. SPS also promote the growth of the pulmonary arteries, pulmonary valve annulus and left ventricular, and it facilitates the preservation of pulmonary valve annulus and reduce the rate of transannular patching in a portion of infants.

Objective To investigate the applicate effects in the treatment of left coronary artery abnormality originated from pulmonary artery(ALCAPA) with two perfusion methods of Medium-low temperature-full flow and Low-temperature-low flow.Methods From April 2010 to August 2018, 51 children with ALCAPA were treated with direct coronary artery trans-plantation in Beijing Anzhen Hospital.According to the circulated perfusion method, All of cases were divided into two groups:the Medium-low temperature full flow(group A) and Low-temperature low flow(group B); All patients underwent ALCAPA correct operation under general anesthesia by intravenous inhalation and extracorporeal circulation , and the combined cardiac malformations at the same period.Results The whole of 51 children, including 27 males and 24 females, the aweraged age was(29.19 ±19.43)months(8-36 months), the aweraged weight was(11.73 ±9.99)kg(7.4 -35.0 kg).The cardiotho-racic ratio(C/T) was 0.70 ±0.09.In group A, 24 patients, including 13 males and 11 females, the aweraged age 3 -36 (28.64 ±16.30) months, the aweraged weight 7.4-31.0(12.25 ±10.33) kg, and the cardiothoracic ratio(C/T) 0.71 ± 0.07.Group B included 27 patients, including 15 males and 12 females, the aweraged age 5-31(25.85 ±16.60) months, the aweraged weight 6.7-35.0(10.38 ±3.67)kg, and the cardiothoracic ratio(C/T) of 0.69 ±0.06.The postoperative ear-ly death were 5 cases in the whole group, there were 3 cases in group A and 2 cases in group B, all of them were died of low cardiac output syndrome.Extracorporeal membrane oxygenation(ECMO) support for 7 cases of 5 in group A and 2 in group B. There was no statistically significant difference in in-hospital mortality between the two groups(P >0.05).The Intraoperative extracorporeal circulation time, ascending aorta occlusion time, the number and amount of myocardial cold arrest fluid perfu-sion, postoperative extracorporeal circulation assistance time, the incidence of ventricular fibrillation, ICU residence time, and ventilator assistance time were significantly lower in group B than group A, all with statistically significant differences(P<0. 05).A total of 42 cases were followed up after the operation, the follow-up time 17(3-29) months and the left ventricular e-jection fraction increased from 0.53 ±0.15 to 0.66 ±0.14(P<0.05), there was no statistically significant difference between two groups.Conclusion The perfusion modes of Low-temperature-low flow in the correct operation of ALCAPA can effectively shorten the time of aortic occlusion , improve the effect of intraoperative myocardial protection , reduce intraoperative visual field return blood volume, and reduce postoperative low cardiac output.To improve the curative effect of operation.

The threshold of toxicological concern (TTC), a risk estimation method based on compound structurally-related toxicity data, has been widely used by many countries and regions for the safety risk assessment of food packaging materials and additives etc. Toxicological risk estimation is of importance in the biological evaluation of medical devices. Application of the TTC approach to leachable from medical devices may reduce or replace some unnecessary biocompatibility tests, but consideration should be taken for contact duration and route differences, which could affect the applicability of TTC. We herein focused on analyzing the eligibility of TTC for its further application in biological evaluation of medical devices.
Equipment and Supplies ; standards ; Food Packaging ; standards ; Risk Assessment ; Toxicological Phenomena

Immunogenicity for medical devices of animal origin is the key and difficult point during immune safety evaluation for these devices. This paper firstly investigated the effect of collagen sponge of animal origin on mouse splenic lymphocyte transformation and proliferation, and then analyzed the influence factors on the MTT method and CFSE method. The results showed that collagen sponge extract cannot significantly induce transformation and proliferation of mouse splenic lymphocyte in vitro.
Animals ; Cells, Cultured ; Collagen ; pharmacology ; Lymphocyte Activation ; drug effects ; Mice ; Porifera ; chemistry ; Spleen ; cytology

To discuss IC50 application in cytotoxicity tests of medical devices, we firstly investigated the vibrating condition and endpoint of MTT method specified in ISO 10993-5: 2009. Furthermore, we demonstrated the application of IC50 in the result evaluation of MTT method. The experimental results show that usage of IC50 in quantitative evaluation of MTT method is feasible.
Equipment and Supplies ; adverse effects ; standards ; Inhibitory Concentration 50 ; Toxicity Tests ; methods

Immunogenicity for medical devices of animal origin is the key and diffi cult point during immune safety evaluation for these devices. This paper firstly investigated the effect of colagen sponge of animal origin on mouse splenic lymphocyte transformation and proliferation, and then analyzed the infl uence factors on the MTT method and CFSE method. The results showed that colagen sponge extract cannot signifi cantly induce transformation and proliferation of mouse splenic lymphocyte in vitro.

ObjectiveContrast research the operative effect of the pulmonary artery banding (PAB) in the congenital heart disease with pulmonary artery hypertension,underwent the single ventricle repair procedure in different age.Methods 49 cases,male 31 and female 18.Age (7.8 ± 3.8 ) years old,weight ( 8.82 ± 4.24) kg,percutaneous blood oxygen saturation ( SPO2 ) 0.90 ± 0.04,preoperative mean pulmonary artery pressure (mPAP) ( 54.6 ± 16.8 ) mm Hg.single ventricle 13cases,tricuspid atresia 12 cases,double outlet of right ventricle with left ventricular dysplasia 11 cases,tricuspid stenosis 5 cases,ventricular imbalance type complete atrioventricular canal defect 5 cases and cross heart cases 3 cases.divided into three groups:≤0.5 years old of 17 cases,0.5 to 2.0 years old of 17 cases,≥2.0 years old 15 cases.All cases taken PAB under anesthesia and cpb,inhaled oxygen concentration 40％,SPO2 0.85,MPAP 20 mmHg.comparatively analysis postoperative SPO2,MPAP,Ventilator using time,ICU stay time and operation mortality of the three groups.ResultsThe postoperative PAP obviously decreased.Three groups of postoperative SPO2,mPAP,ventilator using time,ICU stay time were not significantly different.More than were followed up 6-72 months,1 cases ( 1-2 months) dead in aspiration two months postoperation.the other three cases had been completed Glenn and/or Fontan.ConclusionPAB can effectively reduce the pulmonary artery pressure in the different age children with congenital heart disease and pulmonary artery hypertension,the effect is good.more than 2 years old children still PAB feasible operation,and likely to complete the Glenn and/or Fontan procedure.