Enzymatic bionanocatalysts for combating peri-implant biofilm infections by specific heat-amplified chemodynamic therapy and innate immunomodulation.

Bacterial biofilm-associated infection is a life-threatening emergency contributing from drug resistance and immune escape. Herein, a novel non-antibiotic strategy based on the synergy of bionanocatalysts-driven heat-amplified chemodynamic therapy (CDT) and innate immunomodulation is proposed for specific biofilm elimination by the smart design of a biofilm microenvironment (BME)-responsive double-layered metal-organic framework (MOF) bionanocatalysts (MACG) composed of MIL-100 and CuBTC. Once reaching the acidic BME, the acidity-triggered degradation of CuBTC allows the sequential release of glucose oxidase (GOx) and an activable photothermal agent, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). GOx converts glucose into H2O2 and gluconic acid, which can further acidify the BME to accelerate the CuBTC degradation and GOx/ABTS release. The in vitro and in vivo results show that horseradish peroxidase (HRP)-mimicking MIL-100 in the presence of self-supplied H2O2 can catalyze the oxidation of ABTS into oxABTS to yield a photothermal effect that breaks the biofilm structure via eDNA damage. Simultaneously, the Cu ion released from the degraded CuBTC can deplete glutathione and catalyze the splitting of H2O2 into •OH, which can effectively penetrate the heat-induced loose biofilms and kill sessile bacteria (up to 98.64%), such as E. coli and MRSA. Particularly, MACG-stimulated M1-macrophage polarization suppresses the biofilm regeneration by secreting pro-inflammatory cytokines (e.g., IL-6, TNF-α, etc.) and forming a continuous pro-inflammatory microenvironment in peri-implant biofilm infection animals for at least 14 days. Such BME-responsive strategy has the promise to precisely eliminate refractory peri-implant biofilm infections with extremely few adverse effects.

Synthesis of a Hybrid Composed of Anisotropic Niobate Layers Modified with MoC Nanoparticles.

The hybrid composed of anisotropic niobate layers modified with MoC nanoparticles is synthesized by multistep reactions. The stepwise interlayer reactions for layered hexaniobate induce selective surface modification at the alternate interlayers, and the following ultrasonication leads to the formation of double-layered nanosheets. The further liquid phase MoC deposition with the double-layered nanosheets leads to the decoration of MoC nanoparticles on the surfaces of the double-layered nanosheets. The new hybrid can be regarded as a stacking of the two layers with anisotropically modified nanoparticles. The relatively high temperature in the MoC synthesis causes partial leaching of the grafted phosphonate groups. The exposed surface of the niobate nanosheets due to the partial leaching may interact with MoC to succeed in the hybridization. The hybrid after heating exhibits photocatalytic activity, indicating that this hybridization method can be useful for hybrid synthesis of semiconductor nanosheets and co-catalyst nanoparticles toward photocatalytic application.

SARS-CoV-2 Spike Stem Protein Nanoparticles Elicited Broad ADCC and Robust Neutralization against Variants in Mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global pandemic. The virus is rapidly evolving, characterized by the emergence of several major variants. Stable prefusion spike protein (Pre) is the immunogen in current vaccines but is limited in protecting against different variants. Here, the immune responses induced by the relatively conserved stem subunit (S2) of spike protein versus Pre are investigated. Pre generates the most robust neutralization responses against SARS-CoV-2 variants in vesicular stomatitis virus pseudovirus-based assessment but elicits less antibody-dependent cellular cytotoxicity (ADCC) activity than S2. By contrast, S2 induces the most balanced immunoglobulin G (IgG) antibodies with potent and broad ADCC activity although produces weaker neutralization. The immunogenicity of S2 and Pre improves by incorporating the two proteins into double-layered protein nanoparticles. The resulting protein nanoparticles Pre/S2 elicit higher neutralizing antibodies than Pre alone, and stronger ADCC than S2 alone. Moreover, nanoparticles produce more potent and balanced serum IgG antibodies than the corresponding soluble protein mixture, and the immune responses are sustained for at least four months after the immunization. Thus, the double-layered protein nanoparticles have the potential to be developed into broader SARS-CoV-2 vaccines with excellent safety profiles.

Prototypical Study of Double-Layered Cathodes for Aqueous Rechargeable Static Zn-I2 Batteries.

Aqueous rechargeable zinc-iodine batteries (ZIBs) are promising candidates for grid energy storage because they are safe and low-cost and have high energy density. However, the shuttling of highly soluble triiodide ions severely limits the device's Coulombic efficiency. Herein, we demonstrate for the first time a double-layered cathode configuration with a conductive layer (CL) coupled with an adsorptive layer (AL) for ZIBs. This unique cathode structure enables the formation and reduction of adsorbed I3- ions at the CL/AL interface, successfully suppressing triiodide ion shuttling. A prototypical ZIB using a carbon cloth as the CL and a polypyrrole layer as the AL simultaneously achieves outstanding Coulombic efficiency (up to 95.6%) and voltage efficiency (up to 91.3%) in the aqueous ZnI2 electrolyte even at high-rate intermittent charging/discharging, without the need of ion selective membranes. These findings provide new insights to the design and fabrication of ZIBs and other batteries based on conversion reactions.

IL-Functionalized Mg3Al-LDH as New Efficient Adsorbent for Pd Recovery from Aqueous Solutions.

Palladium is a noble metal of the platinum group metals (PGMs) with a high value and major industrial applications. Due to the scarce palladium resources, researchers' attention is currently focused on Pd ions recovery from secondary sources. Regarding the recovery process from aqueous solutions, many methods were studied, amongst which adsorption process gained a special attention due to its clear advantages. Moreover, the efficiency and the selectivity of an adsorbent material can be further improved by functionalization of various solid supports. In this context, the present work aims at the synthesis and characterization of Mg3Al-LDH and its functionalization with ionic liquid (IL) (Methyltrialkylammonium chloride) to obtain adsorbent materials with high efficiency in Pd removal from aqueous solutions. The maximum adsorption capacity developed by Mg3Al-LDH is 142.9 mg Pd., and depending on the functionalization method used (sonication and co-synthesis, respectively) the maximum adsorption capacity increases considerably, qmax-Mg3Al IL-US = 227.3 mg/g and qmax-Mg3Al IL-COS = 277.8 mg/g.

Use of double-layered covered esophageal stents in post-surgical esophageal leaks and esophageal perforation: Our experience. / Uso de prótesis esofágicas cubiertas de doble malla en fístulas esofágicas postquirúrgicas y perforaciones esofágicas: experiencia en nuestro centro.

INTRODUCTION: The use of esophageal stents for the endoscopic management of esophageal leaks and perforations has become a usual procedure. One of its limitations is its high migration rate. To solve this incovenience, the double-layered covered esophageal stents have become an option. OBJECTIVES: To analyse our daily practice according to the usage of double-layered covered esophageal metal stents (DLCEMS) (Niti S™ DOUBLE™ Esophageal Metal Stent Model) among patients diagnosed of esophageal leak or perforation. METHODS: Retrospective, descriptive and unicentric study, with inclusion of patients diagnosed of esophageal leak or perforation, from November 2010 until October 2018. The main aim is to evaluate the efficacy of DLCEMS, in terms of primary success and technical success. The secondary aim is to evaluate their (the DLCEMS) safety profile. RESULTS: Thirty-one patients were firstly included. Among those, 8 were excluded due to mortality not related to the procedure. Following stent placement, technical success was reached in 100% of the cases, and primary success, in 75% (n=17). Among the complications, stent migration was present in 21.7% of the patients (n=5), in whom the incident was solved by endoscopic means. CONCLUSIONS: According to our findings, DLCEMS represent an alternative for esophageal leak and perforation management, with a high success rate in leak and perforation resolutions and low complication rate, in contrast to the published data. The whole number of migrations were corrected by endoscopic replacement, without the need of a new stent or surgery.

Development of theranostic dual-layered Au-liposome for effective tumor targeting and photothermal therapy.

BACKGROUND: Photothermal therapy (PTT) is an emerging anti-cancer therapeutic strategy that generates hyperthermia to ablate cancer cells under laser irradiation. Gold (Au) coated liposome (AL) was reported as an effective PTT agent with good biocompatibility and excretory property. However, exposed Au components on liposomes can cause instability in vivo and difficulty in further functionalization. RESULTS: Herein, we developed a theranostic dual-layered nanomaterial by adding liposomal layer to AL (LAL), followed by attaching polyethylene glycol (PEG) and radiolabeling. Functionalization with PEG improves the in vivo stability of LAL, and radioisotope labeling enables in vivo imaging of LAL. Functionalized LAL is stable in physiological conditions, and 64Cu labeled LAL (64Cu-LAL) shows a sufficient blood circulation property and an effective tumor targeting ability of 16.4%ID g-1 from in vivo positron emission tomography (PET) imaging. Also, intravenously injected LAL shows higher tumor targeting, temperature elevation in vivo, and better PTT effect in orthotopic breast cancer mouse model compared to AL. The tumor growth inhibition rate of LAL was 3.9-fold higher than AL. CONCLUSION: Based on these high stability, in vivo imaging ability, and tumor targeting efficiency, LAL could be a promising theranostic PTT agent.

Application of double layered end-to-end anastomosis with continuous manual suture for completing digestive tract reconstruction in totally laparoscopic distal gastrectomy.

BACKGROUND: We retrospectively reviewed and consecutively collected the clinical data of distal gastric cancer patients who received surgical treatment, and we discuss the safety and feasibility of double layered end-to-end anastomosis with continuous manual suture to complete digestive tract reconstruction in totally laparoscopic distal gastrectomy. METHODS: We reviewed the clinical data of 41 patients with distal gastric cancer from the gastroenterology department of the Second Affiliated Hospital of Dalian Medical University, from September 2018 to August 2019, who underwent totally laparoscopic distal gastrectomy. During the operation, the method of double layered end-to-end anastomosis with continuous manual suture was used for Billroth type I anastomosis to complete digestive tract reconstruction. All patients have been given a follow-up visit and gastroscopy three months after the operation. The peri-operative clinical information and postoperative follow-up information were collected for analysis, and the clinical application value was evaluated. RESULTS: General information: male(n = 27), female(n = 14), age = 65.02(SD 9.94) years, and BMI = 23.52(SD 2.56) kg/m2, Tumor location: antrum(32,78.0%), angle (6,14.6%), and body (3,7.3%). Clinical stage: I (27, 65.9%), II (7, 17.1%), and III (7, 17.1%). Operative information: operation time = 154.51(SD 33.37) min, anastomosis time = 26.88(SD 5.11) min; intraoperative bleeding = 66.34(SD 48.81) ml; first postoperative ambulation Median = 1(IQR 0) d, first postoperative flatus Median = 3(IQR 2) d, first postoperative diet Median = 3(IQR 1) d, postoperative hospital stay Median = 7(IQR 2) d, and total hospitalization cost = 10,935.00(SD 2205.72)USD. Differentiation degree: high and high-moderate (3,7.32%), moderate and poor-moderate (24, 58.54%), poor differentiation (14, 34.15%), dissected lymph nodes Median = 31(IQR 17), and positive lymph nodes Median = 0(IQR 1). Pathological stage: IA (20, 48.78%), IB (3, 7.32%), IIA (4, 9.76%), IIB (5, 12.20%), IIIA (1, 2.44%), IIIB (3, 7.32%), and IIIC (5, 12.20%). Complications (n = 4): lung infection (1, 2.44%), anastomotic leakage (1, 2.44%), and gastroparesis (2, 4.88%). CONCLUSION: It is safe and feasible in clinical treatment to apply the method of double layered end-to-end anastomosis with continuous manual suture to complete digestive tract reconstruction in totally laparoscopic distal gastrectomy.

Exome sequencing reveals a novel COL2A1 mutation implicated in multiple epiphyseal dysplasia.

Mutations in the COMP, COL9A1, COL9A2, COL9A3, MATN3, and SLC26A2 genes cause approximately 70% of multiple epiphyseal dysplasia (MED) cases. The genetic changes involved in the etiology of the remaining cases are still unknown, suggesting that other genes contribute to MED development. Our goal was to identify a mutation causing an autosomal dominant form of MED in a large multigenerational family. Initially, we excluded all genes known to be associated with autosomal dominant MED by using microsatellite and SNP markers. Follow-up with whole-exome sequencing analysis revealed a mutation c.2032G>A (p.Gly678Arg) in the COL2A1 gene (NCBI Reference Sequence: NM_001844.4), which co-segregated with the disease phenotype in this family, manifested by severe hip dysplasia and osteoarthritis. One of the affected family members had a double-layered patella, which is frequently seen in patients with autosomal recessive MED caused by DTDST mutations and sporadically in the dominant form of MED caused by COL9A2 defect.

Thermal Characteristics of Staggered Double-Layer Microchannel Heat Sink.

The present work numerically studies the thermal characteristics of a staggered double-layer microchannel heat sink (DLMCHS) with an offset between the upper layer of microchannels and lower layer of microchannels in the width direction, and investigates effects of inlet velocity and geometric parameters including the offset of the two layers of microchannels, vertical rib thickness and microchannel aspect ratio on the thermal resistance of the staggered DLMCHS. The present work found that the thermal resistance of the staggered DLMCHS increases with the increasing offset value when the vertical rib thickness is small, but decreases firstly and then increases as the offset value increases when the vertical rib thickness is large enough. Furthermore, the thermal resistance of the staggered DLMCHS decreases with the increasing offset when the aspect ratio is small, but increases with the increasing offset when the aspect ratio is large enough. Thus, for the DLMCHS with a small microchannel aspect ratio and large vertical rib thickness, the offset between the upper layer of microchannels and the lower layer of microchannels in the width direction is a potential method to reduce thermal resistance and improve the thermal performance of the DLMCHS.

Numerical Study of Double-Layered Microchannel Heat Sinks with Different Cross-Sectional Shapes.

This work numerically studies the thermal and hydraulic performance of double-layered microchannel heat sinks (DL-MCHS) for their application in the cooling of high heat flux microelectronic devices. The superiority of double-layered microchannel heat sinks was assessed by a comparison with a single-layered microchannel heat sink (SL-MCHS) with the same triangular microchannels. Five DL-MCHSs with different cross-sectional shapes-triangular, rectangular, trapezoidal, circular and reentrant Ω-shaped-were explored and compared. The results showed that DL-MCHS decreased wall temperatures and thermal resistance considerably, induced much more uniform wall temperature distribution, and reduced the pressure drop and pumping power in comparison with SL-MCHS. The DL-MCHS with trapezoidal microchannels performed the worst with regard to thermal resistance, pressure drop, and pumping power. The DL-MCHS with rectangular microchannels produced the best overall thermal performance and seemed to be the optimum when thermal performance was the prime concern. Nevertheless, the DL-MCHS with reentrant Ω-shaped microchannels should be selected when pumping power consumption was the most important consideration.

Preparation of polyurea/melamine formaldehyde double-layered self-healing microcapsules and investigation on core fraction.

Moisture curing type self-healing microcapsules become more attractive, while instability of active core material crippled the efficiency of self-healing behaviour. Polyurea (PU)/melamine formaldehyde (MF) double-layered self-healing microcapsules containing isophorone diisocyanate (IPDI) core with high and stable core fraction were prepared. The structure, morphology, particle size and distribution were studied with Fourier transform infra-red spectroscopy, optical microscopy, scanning electron microscopy and Mastersizer 3000. The influences of process conditions were investigated to uncover the principle of core fraction and morphology of microcapsules. The core fraction of microcapsules was reduced with the increase of ageing time, and microcapsules prepared with ice-bath, polyetheramine (PEA) and prepolymer of melamine formaldehyde (P-MF) had higher core fraction and better morphology. PEA D230 and 1500 rpm agitation rate were chosen according to optimised trade-offs in the core fraction and morphology of the microcapsules.

Double-Layered Matrix of Shellac Wax-Lutrol in Controlled Dual Drug Release.

Double-layered matrix tablets prepared from shellac wax-lutrol were fabricated using a molding technique, and the release of hydrochlorothiazide and propranolol HCl from the inner tablet or outer layer was studied. The simultaneous determination of dual drug release was measured with first derivative UV spectrophotometry. The tablet containing shellac wax as the outer tablet and lutrol as the inner tablet showed more appropriate drug release and the size of the inner layer influenced the rate of drug release. In addition, the aqueous solubility of the drug and the components of the inner tablet or outer layer affected the drug release behavior. Most of the double-layered tablets exhibited the drug-release pattern which fitted well with zero-order kinetic due to the restriction of the release surface. Biphasic drug release pattern was found in the tablet of which the outer layer rapidly eroded. The drug dissolution data from drug-loaded-outer layer could predict the dissolution time for the outer layer of drug-loaded inner part of double-layered matrix tablet. Incorporation of lutrol increased the drug release from shellac wax matrix, and the zero-order release was attained by fabricating it into a double-layered tablet.

SLC26A2 disease spectrum in Sweden - high frequency of recessive multiple epiphyseal dysplasia (rMED).

Diastrophic dysplasia (DTD) is an autosomal recessive skeletal dysplasia caused by SLC26A2 mutations. Clinical features include short stature, joint contractures, spinal deformities, and cleft palate. SLC26A2 mutations also result in other skeletal dysplasias, including the milder recessive multiple epiphyseal dysplasia (rMED). DTD is overrepresented in Finland and we speculated that this may have influenced the prevalence and spectrum of SLC26A2-related skeletal conditions also in Sweden. We reviewed the patient registry at Department of Clinical Genetics, Karolinska University Hospital, Stockholm to identify subjects with SLC26A2 mutations. Seven patients from six families were identified; clinical data were available for six patients. All but one patient had one or two copies of the Finnish SLC26A2 founder mutation IVS1+2T>C. Arg279Trp mutation was present in compound heterozygous form in five patients with phenotypes consistent with rMED. Their heights ranged from -2.6 to -1.4 standard deviation units below normal mean and radiographic features included generalised epiphyseal dysplasia and double-layered patellae. Two rMED patients had hypoplastic C2 and cervical kyphosis, a severe manifestation previously described only in DTD. Our study confirms a high prevalence of rMED in Sweden and expands the phenotypic manifestations of rMED.

Organic-aqueous crossover coating process for the desmopressin orally disintegrating microparticles.

The purpose of the present study was to prepare desmopressin orally disintegrating microparticles (ODMs) using organic-aqueous crossover coating process which featured an organic sub-coating followed by an aqueous active coating. Sucrose beads and hydroxypropyl cellulose (HPC) were used as inert cores and a coating material, respectively. Characterizations including size distribution analysis, in-vitro release studies and in-vitro disintegration studies were performed. A pharmacokinetic study of the ODMs was also conducted in eight beagle dogs. It was found that sucrose beads should be coated using organic solvents to preserve their original morphology. For the active coating, the aqueous coating solution should be used for drug stability. When sucrose beads were coated using organic-aqueous crossover coating process, double-layer ODMs with round shapes were produced with detectable impurities below limit of US Pharmacopeia. The median size of ODMs was 195.6 µm, which was considered small enough for a good mouthfeel. The ODMs dissolved in artificial saliva within 15 s because of hydrophilic materials including sucrose and HPC in the ODMs. Because of its fast-dissolving properties, 100% release of the drug was reached within 5 min. Pharmacokinetic parameters including Cmax and AUC24 indicated bioequivalence of the ODMs and the conventional immediate release tablets. Therefore, by using the organic-aqueous crossover coating process, double-layer ODMs were successively prepared with small size, round shapes and good drug stability.

Amniotic membrane extract-loaded double-layered wound dressing: evaluation of gel properties and wound healing.

The conservative single-layered wound dressing system is decomposed when mixed in polyvinyl alcohol (PVA) solution, which means it cannot be used with a temperature-sensitive drug. The goal of this investigation was to make an amniotic membrane extract (AME)-loaded double-layered wound dressing with an improved healing result compared to the conservative single-layered wound dressing systems. The double-layered wound dressing was developed with PVA/sodium alginate using a freeze-melting technique; one layer was PVA layer and the other was the drug-loaded sodium alginate layer. Its gel properties were assessed compared to single-layered wound dressings. Moreover, in vivo wound-healing effects and histopathology were calculated compared to commercial products. The double-layered wound dressing gave a similar gel fraction and Young's module as single-layered wound bandages developed with only PVA, and a similar inflammation ability and WVTR as single-layered wound dressings developed with PVA and sodium alginate. Our data indicate that these double-layered wound bandages were just as swellable, but more elastic and stronger than single-layered wound dressings comprised of the same polymers and quantities, possibly giving an acceptable level of moisture and accumulation of exudates in the wound zone. Compared to the commercial product, the double-layered wound dressing comprising 6.7% PVA, 0.5% sodium alginate and 0.01% AME significantly enhanced the wound-healing effect in the wound-healing test. Histological investigations showed that superior full-thickness wound-healing effects compared to the commercial product. Therefore, the double-layered wound dressing would be an outstanding wound-dressing system with improved wound healing and good gel property.

Continence outcomes following robotic radical prostatectomy: Our experience from 150 consecutive patients.

INTRODUCTION: Urinary continence is an important outcome parameter after robot assisted radical prostatectomy (RARP). We evaluated the continence outcomes following RARP using a double-layered urethrovesical reconstruction. MATERIALS AND METHODS: One hundred fifty consecutive patients undergoing RARP and double-layered urethrovesical reconstruction were prospectively studied for preoperative, intraoperative and post operative parameters. Key points followed during surgery were: Minimal dissection of sphincteric complex, preservation of puboprostatic ligament, selective ligation of deep venous complex and both posterior and anterior reconstruction using the Von Velthoven stitch. Intraoperative bladder fill test was done at the end of anastomosis to rule out urine leak. Check cystogram was done prior to catheter removal in the outpatient department. Patients were subsequently followed at regular intervals regarding the status of urinary continence. All patients irrespective of adjuvant therapy were included in the analysis. RESULTS: The mean age was 64 years (standard deviation ± 6.88), and mean serum PSA was 20.2 ng/ml. The mean BMI was 25.6 (SD: ±3.84). The mean prostate weight was 44.09 gm (range 18-103 gm, SD: ±15.59). Median days to catheter removal after surgery was 7 (range 4-14 days) days. Cystographically determined urinary leaks were seen in two patients. Urine leak was managed by delaying catheter removal for 1 week. Minimum 6 month follow up was available in 126 patients. 'No pad' status at 1 week, 1 month, 3 months, 6 months and 1 year was 15.1%, 54.9%, 78%, 90.5% and 94.1%, respectively. CONCLUSION: Excellent continence outcomes are observed in patients undergoing double-layered urethrovesical reconstruction.

Phytolacca americana extract as a quality-enhancing factor for biodegradable double-layered films based on furcellaran and gelatin - Property assessment.

For the first time, novel active double-layered films based on furcellaran (FUR) and gelatin (GEL) with the addition of Phytolacca americana (PA) extract were obtained. The 1st layer consisted of FUR and GEL, while the aqueous extract of P. americana berries was added in three different concentrations to the 2nd FUR-based layer. The films were characterised by good mechanical (TS range of 0.0011-0.0013 MPa, EAB range between 30.38 %-33.51 %) and water properties (WVTR range of 574.74-588.49 g/m2xd). Structural analysis (SEM and AFM) confirmed good film structure: regular, without cracks or air bubbles. The films showed antioxidant activity tested via the Folin-Ciocâlteu method (4.77-20.70 mg GAExg-1), FRAP assay (0.18-3.40 mM TExg-1) and CUPRAC assay (48.63-53.99 mM TExg-1). The film with the highest PA concentration (6 %) demonstrated the ability to neutralise free radicals, DPPH• and ABTS2+•, at the levels of 1.97 % and 17.34 %, respectively. The ecotoxicity test performed on Lepidium sativum seeds confirmed the lack of ecotoxic film aspects. The biodegradation test indicated that the films are biodegradable. The obtained films can be a good alternative to plastic packaging films (used in the food packaging industry), which are currently a global problem related to the development of post-consumer plastics.

Design and performance of double-layered artificial chordae.

Surgical repair with artificial chordae replacement has emerged as a standard treatment for mitral regurgitation. Expanded polytetrafluoroethylene (ePTFE) sutures are commonly employed as artificial chordae; however, they have certain limitations, such as potential long-term rupture and undesired material/tissue response. This study introduces a novel approach to artificial chordae design, termed the New Artificial Chordae (NAC), which incorporates a double-layered structure. The NAC comprises a multi-strand braided core composed of ultra-high molecular weight polyethylene (UHMWPE) fibers as the inner core, and an outer tube made of hydrophobic porous ePTFE. Compared to traditional ePTFE sutures, NAC exhibits increased flexibility, enhanced tensile strength, longer elongation and improved fatigue resistance. Moreover, NAC exhibits a more hydrophobic surface, which contributes to enhanced hemocompatibility. The study also includes in vivo investigations conducted on animal models to evaluate the biocompatibility and functional efficacy of the artificial chordae. These experiments demonstrate the enhanced durability and biocompatibility of the NAC, characterized by improved mechanical strength, minimal tissue response and reduced thrombus formation. These findings suggest the potential application of NAC as a prosthetic chordae replacement, offering promising prospects to address the limitations associated with current artificial chordae materials and providing novel ideas and approaches for the development of sustainable and biocompatible regenerative biomaterials.