Biocompatibility and mineralization potential of new calcium silicate cements.

Background/purpose: As calcium silicate cements (CSCs) have been successfully used in various types of vital pulp therapy, many new CSC products have been developed. The aim of this study was to evaluate the biocompatibilities and mineralization potential of new CSC. The experimental materials were NeoMTA Plus and EndoSequence Root Repair Material-Fast Set Putty (ERRM-FS) which were compared to ProRoot MTA. Materials and methods: In vitro, the effects of the new CSC on stem cells were evaluated. Each CSC was prepared for cell viability testing, alkaline phosphatase (ALP) assay, and calcium ion release assay. In vivo, the exposed pulp model was used for the partial pulpotomy procedure. Thirty-six teeth were treated with three materials: ProRoot MTA, NeoMTA Plus, or ERRM-FS. After four weeks, the teeth were extracted and processed for histologic analysis. Dentin bridge formation, pulp inflammation, and odontoblastic cell layer were evaluated and the area of newly formed calcific barrier of each group was measured. Results: Three CSCs demonstrated similar cell viability on stem cells and the levels of ALP and calcium release were not significantly different between tested materials. ProRoot MTA and ERRM-FS showed better tissue healing process than NeoMTA Plus after partial pulpotomy, in terms of quality of calcific barrier and pulp inflammation. The outcomes from measuring newly formed calcific area demonstrated no significant differences between the materials. Conclusion: NeoMTA Plus and ERRM-FS displayed similar biocompatibilities and mineralization potential compared to ProRoot MTA. Therefore, these new CSCs can be used as desirable alternatives to ProRoot MTA.

Novel 3D Printed Resin Crowns for Primary Molars: In Vitro Study of Fracture Resistance, Biaxial Flexural Strength, and Dynamic Mechanical Analysis.

This study evaluated the fracture resistance, biaxial flexural strength (BFS), and dynamic mechanical analysis (DMA) of three-dimensional (3D) printing resins for the esthetic restoration of primary molars. Two 3D printing resins, Graphy (GP) and NextDent (NXT), and a prefabricated zirconia crown, NuSmile (NS), were tested. GP and NXT samples were 3D printed using the workflow recommended by each manufacturer. Data were collected and statistically analyzed. As a result of the fracture resistance test of 0.7-mm-thick 3D printed resin crowns with a thickness similar to that of the NS crown, there was no statistically significant difference among GP (1491.6 ± 394.6 N), NXT (1634.4 ± 289.3 N), and NS (1622.8 ± 323.9 N). The BFS of GP was higher for all thicknesses than that of NXT. Both resins showed high survival probabilities (more than 90%) when subjected to 50 and 150 MPa. Through DMA, the glass transition temperatures of GP and NXT were above 120 °C and the rheological behavior of GP and NXT according to temperature and frequency were analyzed. In conclusion, GP and NXT showed optimum strength to withstand bite forces in children, and 3D printed resin crowns could be an acceptable option for fixed prostheses of primary teeth.

Image-guided in situ cancer vaccination with combination of multi-functional nano-adjuvant and an irreversible electroporation technique.

Cancer immunotherapy is a next-generation treatment strategy; however, its side effects limit its clinical translation. Here, a novel combination of a multi-functional nano-adjuvant (M-NA) prepared with an iron oxide/gold core and a cationic polymer shell via multilayer synthesis with CpG oligodeoxynucleotide (CpG-ODN) electrostatically complexed on its surface, and irreversible electroporation (IRE) technique was developed for effective image-guided in situ cancer vaccination. The M-NA can be retained long-term in the dense tumoral extracellular matrix after intratumoral injection and internalized by antigen-presenting cells (APCs). The IRE can induce immunogenic cell death. Indeed, in a mouse tumor model, the M-NA showed longer tumor retention time than free CpG-ODN. Compared with other treatments, the combined treatment significantly inhibited tumor growth with 100% survival rate for ∼60 days. The therapy induced the activation of cytotoxic lymphocytes and the maturation of APCs in vivo. This treatment could be effective in image-guided local cancer immunotherapy.

Assessment of Real-Time Active Noise Control Devices in Dental Treatment Conditions.

Dental clinics are exposed to various uncomfortable noises. The aim of this study was to quantify the effectiveness of active noise control devices in dental treatment conditions. Two types of commercial headsets (Airpods Pro, QC30) and two types of dental headsets (Alltalk, Quieton Dental) were used for the experiment. Three sounds (high-speed handpiece, low-speed handpiece, and suction system) were measured at three different distances from the dental teeth model, typodont. The distances of 10, 40, and 70 cm reflected the positions of the patient, assistant, and practitioner's ears, respectively. Sound analysis was performed, and the significance of differences in the maximum noise level using each device was determined with the Kruskal−Wallis test. Dental noise was characterized by the peak in sound pressure level (SPL) at 4−5 kHz and >15 kHz frequencies. The commercial headsets efficiently blocked 1 kHz and 10 kHz of noise. The dental headsets efficiently reduced 4−6 and >15 kHz noise. Quieton had the highest maximum SPL in all situations and positions among the four devices. For a better dental clinic, however, active noise control devices more suitable for the characteristics of dental noise should be developed.

A Small Molecule That Promotes Cellular Senescence Prevents Fibrogenesis and Tumorigenesis.

Uncontrolled proliferative diseases, such as fibrosis or cancer, can be fatal. We previously found that a compound containing the chromone scaffold (CS), ONG41008, had potent antifibrogenic effects associated with EMT or cell-cycle control resembling tumorigenesis. We investigated the effects of ONG41008 on tumor cells and compared these effects with those in pathogenic myofibroblasts. Stimulation of A549 (lung carcinoma epithelial cells) or PANC1 (pancreatic ductal carcinoma cells) with ONG41008 resulted in robust cellular senescence, indicating that dysregulated cell proliferation is common to fibrotic cells and tumor cells. The senescence was followed by multinucleation, a manifestation of mitotic slippage. There was significant upregulation of expression and rapid nuclear translocation of p-TP53 and p16 in the treated cancer cells, which thereafter died after 72 h confirmed by 6 day live imaging. ONG41008 exhibited a comparable senogenic potential to that of dasatinib. Interestingly, ONG41008 was only able to activate caspase-3, 7 in comparison with quercetin and fisetin, also containing CS in PANC1. ONG41008 did not seem to be essentially toxic to normal human lung fibroblasts or primary prostate epithelial cells, suggesting ONG41008 can distinguish the intracellular microenvironment between normal cells and aged or diseased cells. This effect might occur as a result of the increased NAD/NADH ratio, because ONG41008 restored this important metabolic ratio in cancer cells. Taken together, this is the first study to demonstrate that a small molecule can arrest uncontrolled proliferation during fibrogenesis or tumorigenesis via both senogenic and senolytic potential. ONG41008 could be a potential drug for a broad range of fibrotic or tumorigenic diseases.

Combination of Metal-Phenolic Network-Based Immunoactive Nanoparticles and Bipolar Irreversible Electroporation for Effective Cancer Immunotherapy.

To circumvent the limitations of conventional cancer immunotherapy, it is critical to prime antigen-presenting cells (APCs) to initiate the cancer-immune cycle. Here, the authors develop a metal-phenolic network (MPN)-based immunoactive nanoparticle in combination with irreversible electroporation (IRE) for an effective cancer immunotherapy. The MPN nanoparticles are synthesized by coordinating tannic acid with manganese (Mn) ions, and subsequent coating with CpG-oligodeoxynucleotides (CpG-ODNs) via hydrogen bonding. The CpG-ODN-coated Mn-phenolic network (CMP) nanoparticles are effectively internalized into macrophages, a type of APCs, and successfully trigger M1 polarization to promote release of proinflammatory cytokines. Notably, the CMP nanoparticles demonstrate an extended retention time period than the free CpG-ODN in the tumor. The tumor microenvironment tailored bipolar IRE, enhances the therapeutic efficacy by significantly broadening the ablation zone, which further increases immunogenic cell death (ICD). Ultimately, the simultaneous CMP nanoparticles and IRE treatment successfully inhibit tumor growth and prolong survival in a mouse tumor model. Thus, CMP nanoparticles are empowered with Mn and CpG-ODN immunomodulators and the tumor microenvironment tailored bipolar IRE will be a new tool for effective cancer immunotherapy to treat intractable malignancies.

Comparative study of pulpal responses to ProRoot MTA, Vitapex, and Metapex in canine teeth.

BACKGROUND/PURPOSE: ProRoot MTA, Vitapex, and Metapex are widely used for pulp treatment of primary tooth. The aim of this study was to compare the pulpal responses to ProRoot MTA, Vitapex, and Metapex in a canine model of pulpotomy. MATERIALS AND METHODS: Pulpotomy procedure was performed to 34 teeth (21 incisors and 13 premolars) and ProRoot MTA, Vitapex or Metapex was applicated to artificially exposed pulp tissues. After 13 weeks, the teeth were extracted and processed with hematoxylin-eosin staining for histologic evaluation. All specimens were evaluated in several categorys related to calcific barrier, inflammatory responses and the area of calcific barrier formation was measured. RESULTS: Most of the specimens in the ProRoot MTA group developed a calcific barrier at the pulp amputation site and showed a low level of inflammatory response. However, in comparison to ProRoot MTA group, a small amount of calcific barrier formed in Vitapex and Metapex groups. CONCLUSION: This in vivo study found that Vitapex and Metapex induced similar pulpal responses but showed poor outcomes compared with using ProRoot MTA. Vitapex and Metapex are therefore not good substitutes for ProRoot MTA in direct pulp capping and pulpotomy.

The Piston Elastic: A Novel Device for Treating Entrapped Ectopic Permanent Molars.

Ectopic eruption of the permanent molar may absorb the distal root of the primary second molar and may result in a decreased arch length or delayed eruption of the permanent tooth, requiring timely treatment. Therefore, we devised an effective and convenient method to unlock the entrapped tooth using a novel device called a "piston-elastic". This case report aims to explain the design and clinical application of this piston-elastic and to describe successful cases. Three patients (aged 6, 13, and 16 years) with ectopically erupted maxillary and mandibular molars, respectively, were treated with a piston-elastic. It was bound to the locked molar to improve the eruption path. After a certain time period, the repulsive force pushed the surface of the adjacent tooth, improving the eruption path of the entrapped tooth. The piston-elastic is a novel device that simply and effectively changes the direction of eruption of ectopically entrapped molars. As it can be manufactured and attached to the chair side, impression acquisition on a model cast and laboratory procedures are unnecessary. Compared to existing methods, the piston-elastic can be easily produced and delivered, causes little irritation, and is inexpensive.

Human nasal septal chondrocytes (NSCs) preconditioned on NSC-derived matrix improve their chondrogenic potential.

BACKGROUND: Extracellular matrix (ECM) has a profound effect on cell behaviors. In this study, we prepare a decellularized human nasal septal chondrocyte (NSC)-derived ECM (CHDM), as a natural (N-CHDM) or soluble form (S-CHDM), and investigate their impact on NSCs differentiation. METHODS: N-CHDM, S-CHDM were obtained from NSC. To evaluate function of NSC cultured on each substrate, gene expression using chondrogenic marker, and chondrogenic protein expression were tested. Preconditioned NSCs-loaded scaffolds were transplanted in nude mice for 3 weeks and analyzed. RESULTS: When cultivated on each substrate, NSCs exhibited similar cell spread area but showed distinct morphology on N-CHDM with significantly lower cell circularity. They were highly proliferative on N-CHDM than S-CHDM and tissue culture plastic (TCP), and showed more improved cell differentiation, as assessed via chondrogenic marker (Col2, Sox9, and Aggrecan) expression and immunofluorescence of COL II. We also investigated the effect of NSCs preconditioning on three different 2D substrates while NSCs were isolated from those substrates, subsequently transferred to 3D mesh scaffold, then cultivated them in vitro or transplanted in vivo. The number of cells in the scaffolds was similar to each other at 5 days but cell differentiation was notably better with NSCs preconditioned on N-CHDM, as assessed via real-time q-PCR, Western blot, and immunofluorescence. Moreover, when those NSCs-loaded polymer scaffolds were transplanted subcutaneously in nude mice for 3 weeks and analyzed, the NSCs preconditioned on the N-CHDM showed significantly advanced cell retention in the scaffold, more cells with a chondrocyte lacunae structure, and larger production of cartilage ECM (COL II, glycosaminoglycan). CONCLUSIONS: Taken together, a natural form of decellularized ECM, N-CHDM would present an advanced chondrogenic potential over a reformulated ECM (S-CHDM) or TCP substrate, suggesting that N-CHDM may hold more diverse signaling cues, not just limited to ECM component.

In Vivo Evaluation of Decellularized Human Tooth Scaffold for Dental Tissue Regeneration.

Conventional root canal treatment may result in loss of tooth vitality, which can lead to unfavorable treatment outcomes. Notably, a ceased tooth development of immature permanent teeth with open apices, regeneration of periodontal ligaments (PDL), and pulp is highly expected healing process. For regeneration, the scaffold is one of the critical components that carry biological benefits. Therefore, this study evaluated a decellularized human tooth as a scaffold for the PDL and pulp tissue regeneration. A tooth scaffold was fabricated using an effective decellularization method as reported in previous studies. PDL stem cells (PDLSCs) and dental pulp stem cells (DPSCs) obtained from human permanent teeth were inoculated onto decellularized scaffolds, then cultured to transplant into immunosuppressed mouse. After 9 weeks, PDLSCs and DPSCs that were inoculated onto decellularized tooth scaffolds and cultured in an in vivo demonstrated successful differentiation. In PDLSCs, a regeneration of the cementum/PDL complex could be expected. In DPSCs, the expression of genes related to revascularization and the hard tissue regeneration showed the possibility of pulp regeneration. This study suggested that the potential possible application of decellularized human tooth could be a scaffold in regeneration PDL and pulp tissue along with PDLSCs and DPSCs, respectively, as a novel treatment method.

Prognostic factors for the survival of primary molars following pulpotomy with mineral trioxide aggregate: a retrospective cohort study.

OBJECTIVES: The aim of the present study was to evaluate potential factors influencing the success rates of mineral trioxide aggregate (MTA) pulpotomy performed in primary molars. MATERIALS AND METHODS: A total of 347 teeth treated between March 2012 and December 2016 in 258 patients, with a mean age of 5.3 ± 1.7 years, were included in the analysis. Kaplan-Meier analyses were used to analyze were used time to failure. Multivariate Cox regression analysis with shared frailty was used to evaluate the clinical factors associated with failures. RESULTS: The mean (standard deviation) follow-up period was 35.8 (19.6) months. Within 84 months, the survival rate was 87.1%. In multivariate Cox regression, treatment performed in lower primary molars had a lower survival rate than upper primary molars (hazard ratio [HR] = 3.38, P = 0.012). Caries extension below the cemento-enamel junction had more risk of failure (HR = 10.9, P < 0.001). Final restoration using resin-modified glass ionomer or amalgam (direct filling) had a lower survival rate than stainless steel crown (HR = 5.62, P = 0.002). CONCLUSIONS: Clinical variables such as arch type, degree of caries extension, and type of final restoration may affect the survival of primary molars following MTA pulpotomy. CLINICAL RELEVANCE: The results of this study indicate that specific clinical variables can be used to predict the prognosis of MTA pulpotomy in primary teeth, and estimate the risk of treatment failure. Assessments of these variables should be performed in the context of evidence-based clinical decision making.

Cationic Nanoparticle-Mediated Activation of Natural Killer Cells for Effective Cancer Immunotherapy.

Natural killer (NK) cells have been recognized as a next-generation therapy for cancer as they are less likely to trigger adverse events (e.g., cytokine storm or graft-versus-host disease) than T cell-based therapeutics. Although NK cell activation strategies through genetic engineering and cytokine treatment have been actively studied for successful cancer treatment, the approaches are inefficient, expensive, and involve complex processing. Here, we developed a facile and efficient method of activating NK cells using cationic nanoparticles (cNPs). The cytotoxic activity of cNP-treated primary NK and NK-92MI cells against triple-negative breast cancer cells was over 2-fold higher than that of control NK cells in vitro. Molecular biological analyses confirmed that cNPs altered the expression of CCR4 and CXCR4 of NK cells that function as chemokine receptors. In vitro live cell imaging showed that the NK cells treated with cNPs were better than control NK cells at interacting with cancer cells. Consistent with these in vitro results, cNP-treated NK cells effectively inhibited tumor growth in an in vivo tumor animal model of triple-negative breast cancer. Additionally, NK cells treated with cNPs were tracked effectively in vivo by magnetic resonance imaging. Thus, cNP-mediated activation of NK cells has great potential as an NK cell-based cancer immunotherapy. Most of all, activating NK cells using cNPs has a great advantage over conventional methods in that immune cells can be activated by a one-step facile process with exogenously charged nanomaterials, without the need for genetic engineering or cytokine treatment.

Enhanced mechanical and biological characteristics of PLLA composites through surface grafting of oligolactide on magnesium hydroxide nanoparticles.

Poly(l-lactic acid) (PLLA) is a biocompatible and biodegradable polymer that has received much attention as a biomedical material. However, PLLA also produces by-products that acidify the surrounding tissues during in vivo degradation, which induces inflammatory responses. To overcome these problems, magnesium hydroxide nanoparticles (nano-magnesium hydroxide; nMH) were added to the PLLA matrix as a bioactive filler that can suppress inflammatory responses by neutralizing the acidified environment caused by the degradation of PLLA. Despite the advantages of nMH, the strong cohesion of these nanoparticles toward each other makes it difficult to manufacture a polymer matrix containing homogeneous nanoparticles through thermal processing. Here, we prepared two types of surface-modified nMH with oligolactide (ODLLA) utilizing grafting to (GT) and grafting from (GF) strategies to improve the mechanical and biological characteristics of the organic-inorganic hybrid composite. The incorporation of surface-modified nMH not only enhanced mechanical properties, such as Young's modulus, but also improved homogeneity of magnesium hydroxide particles in the PLLA matrix due to the increase in interfacial interaction. Additionally, the PLLA composites with surface-modified nMH exhibited reduced bulk erosion during hydrolytic degradation with lower cytotoxicity and immunogenicity. Hemocompatibility tests on the PLLA composites with nMH showed a higher albumin to fibrinogen ratio (AFR) and a lower influence of platelet activation, when compared with unmodified control samples. Taken all together, the surface-modified nMH could be seen to successfully improve the physical and biological characteristics of polymer composites. We believe this technology has great potential for the development of hybrid nanocomposites for biomedical devices, including cardiovascular implants.

An osteoconductive PLGA scaffold with bioactive ß-TCP and anti-inflammatory Mg(OH)2 to improve in vivo bone regeneration.

Poly(lactic-co-glycolic acid) (PLGA) has been widely used as a biomaterial for pharmaceutical and medical applications. However, the decomposition products of PLGA are known to acidify the surrounding tissue of the implanted site, causing an inflammatory response. Previously, we developed PLGA/inorganic nanocomposites and optimized the amounts of inorganic compounds, ß-tricalcium phosphate (ß-TCP) and magnesium hydroxide [Mg(OH)2], in terms of osteogenesis of normal human osteoblasts and anti-inflammatory responses of preosteoclastic cells in vitro. In this study, the potential of the optimized PLGA/ß-TCP/Mg(OH)2 nanocomposite (TCP/MH) to promote bone repair through osteoinductive, osteoconductive, and anti-inflammatory abilities was assessed using a bone defect in a rat humeral defect model. PLGA nanocomposites with or without inorganic compounds, PLGA, ß-TCP, MH, and TCP/MH were prepared through one-step bulk modification using a twin-screw extruder. The resulting TCP/MH nanocomposite successfully enhanced the bone regeneration rate for allowing complete bone defect healing with significantly suppressed inflammatory responses. Taken together, the organic and inorganic bioactive nanocomposite developed in this study, TCP/MH, is a promising material in orthopedic implantation.

Dental complications associated with neonatal intubation in preterm infants.

This paper describes the potential oral complications in preterm infants who have undergone orotracheal intubation. Neonatal intubation may have adverse effects on the developing deciduous teeth, oral soft tissues, and even the permanent teeth. However, endotracheal intubation may be essential for the survival of premature infants, owing to incomplete tracheal development. Excessive pressure to the oral tissue must be avoided, in cases where orotracheal intubation is inevitable. Moreover, the potential oral complications must be considered when neonatal intubation is performed for the patient's survival, and subsequent reevaluation and proper oral health care are needed.

Correlation between Dental Maturity and Body Mass Index in Korean Children.

Objective: The aim of this study was to determine relationships between dental maturity and body mass index (BMI) in Korean children. Study Design: 600 Korean children aged between 5 and 10 years for whom panoramic radiographs have been obtained between 2010 and 2017 were selected. Subjects were divided into four weight-status groups: underweight, normal weight, overweight, and obese. Five lower-left permanent teeth were observed and rated. The stage of each tooth was converted into a score using the table suggested by Demirjian, and the sum of these scores was designated as the 'maturity score'. Results: This study found statistically significant differences in dental maturity between the weight groups (analysis of variance, P=0.003), with the maturity score being higher in the obese group than in normal-weight subjects (Tukey's post-hoc test, P=0.004). The linear regression showed a positive association between BMI and the maturity score after adjusting for sex and age (ß=0.34, P<0.001). The linear regression coefficient was higher in girls (ß=0.61, P<0.001) than in boys (ß=0.31, P=0.02). Conclusions: These data suggest that dental maturation is positively associated with BMI in Korean children. Since many treatment decisions are made in relation to dental maturity, these findings may have implications for pediatric dental care.

Decellularized human periodontal ligament for periodontium regeneration.

Regenerating the periodontal ligament (PDL) is a crucial factor for periodontal tissue regeneration in the presence of traumatized and periodontally damaged teeth. Various methods have been applied for periodontal regeneration, including tissue substitutes, bioactive materials, and synthetic scaffolds. However, all of these treatments have had limited success in structural and functional periodontal tissue regeneration. To achieve the goal of complete periodontal regeneration, many studies have evaluated the effectiveness of decellularized scaffolds fabricated via tissue engineering. The aim of this study was to fabricate a decellularized periodontal scaffold of human tooth slices and determine its regeneration potential. We evaluated two different protocols applied to tooth slices obtained from human healthy third molars. The extracellular matrix scaffold decellularized using sodium dodecyl sulfate and Triton X-100, which are effective in removing nuclear components, was demonstrated to preserve an intact structure and composition. Furthermore, the decellularized scaffold could support repopulation of PDL stem cells near the cementum and expressed cementum and periodontal-ligament-related genes. These results show that decellularized PDL scaffolds of human teeth are capable of inducing the proliferation and differentiation of mesenchymal stem cells, thus having regeneration potential for use in future periodontal regenerative tissue engineering.

Fabrication of bacterial cellulose-collagen composite scaffolds and their osteogenic effect on human mesenchymal stem cells.

Scaffold plays a critical role in stem cell differentiation and tissue regeneration. Composite scaffolds composed of bacterial cellulose (BC) and collagen (Col) in different ratios (1:1, 3:1, 5:1) were fabricated in this study. The composite scaffolds exhibit a well-organized interconnected porous structure, significantly better physical stability than Col scaffold, and more water uptake up to 400%. They were also favorable with cell attachment and growth. After osteogenic induction of umbilical cord blood derived mesenchymal stem cells (UCB-MSCs) for 3 weeks, we found more up-regulated osteogenic markers (collagen type 1, osteocalcin, bone sialoprotein) and significantly elevated proteins and calcium deposition, particularly with BC/Col (5:1) scaffold. When PKH-26 pre-labelled MSC-loaded scaffolds were subcutaneously transplanted in a mouse model, they showed many PKH-26-labelled cells and positive signals of α-smooth muscle actin, for neovascularization in the BC/Col (5:1). The current work demonstrates that our BC/Col composites may be promising as a bone tissue-engineered scaffold.

Augmented re-endothelialization and anti-inflammation of coronary drug-eluting stent by abluminal coating with magnesium hydroxide.

Drug-eluting stents (DESs) have been widely used as a treatment approach for coronary artery diseases. Generally, conventional DESs were fully covered with drugs and biodegradable polymers on both abluminal and luminal layers (i.e., conformal coating). However, uncontrolled drug release from the luminal drug-coating layer of the stent is known to inhibit re-endothelialization. Furthermore, the acidification of the surrounding tissue by the decomposed coating polymer causes inflammation, resulting in restenosis and late thrombosis. To overcome these limitations, here we demonstrated a functional DES coated with poly(lactic-co-glycolic acid) (PLGA), sirolimus (SRL), and magnesium hydroxide (Mg(OH)2, MH) precisely only on the abluminal layer. The acidic neutralization effect of MH was elucidated by measuring the pH change of the fabricated film in PBS solution. In an in vitro cell study, the stent coated with MH exhibited higher compatibility with human coronary artery endothelial cells (ECs) and a lower inflammation score as compared to the control stent. Finally, in an in vivo large porcine model, the abluminal coated DES with SRL and MH showed excellent re-endothelialization and anti-inflammatory and anti-thrombotic effects. In conclusion, it is believed that this approach has great potential for the development of functional DES for the treatment of cardiovascular diseases.

One step bulk modification of poly(L-lactic acid) composites with functional additives to improve mechanical and biological properties for cardiovascular implant applications.

Poly(L-lactic acid) (PLLA) has been widely used as a promising biomaterial in biomedical applications due to its biodegradability and high mechanical strength. However, because of the inherent brittleness, low impact resistance, and weak thermal stability of PLLA, the modification process is usually required to utilize it for biomedical devices. Furthermore, acidic byproducts resulting from the hydrolysis of PLLA after implantation reduce the pH of the surrounding environment and cause inflammatory responses in the implanted area, leading to the failure of their clinical applications. To this end, here, we demonstrate a novel modification process for the PLLA composite with various functional additives, such as cis-aconitic anhydride (AA), triacetin (TA), isosorbide derivative (ISB), and/or Pluronic® F127 (F). The modified PLLA composite with TA and F (PLLA/TF) showed significantly improved elongation at break and Young's modulus and retained tensile strength. Moreover, incorporating magnesium hydroxide (MH) nanoparticles (PLLA/TFMH) significantly reduced acid-induced inflammation responses caused by the acidic degradation products of PLLA. Reduced plasma protein adsorption was observed in the PLLA/TFMH. These results suggest that the one step bulk modification of biodegradable PLLA using TA, F, and MH will have great potential in cardiovascular implant applications.