Poly L-lactic Acid Research Articles

Comparative Bulk RNA-Seq Analysis of Poly-l-Lactic Acid Versus Calcium Hydroxylapatite Reveals a Novel, Adipocyte-Mediated Regenerative Mechanism of Action Unique to PLLA.

Injectable biostimulators are widely used to improve facial aging signs. This study was performed to compare the genetic pathways affected by 2 different injectable biostimulators. Randomized 13-week study (n = 21) comparing gene expression after poly l-lactic acid (PLLA-SCA) and calcium hydroxylapatite (CaHA-R) injections (baseline [BL] and Day 28) as treatment of nasolabial fold wrinkles. Punch biopsy was performed at BL and day 90; RNA was isolated, gene expression was analyzed, and bulk RNA sequencing performed. Data from both pathways were studied using the Search Tool for Retrieval of Interacting Genes/Proteins and Reactome databases. Analysis at Day 0 and Day 90 showed differing gene regulation for PLLA-SCA and CaHA-R (after accounting for minor differences at BL, p < .05 at Day 90 for 9-12 genes). PLLA-SCA uniquely correlates with genes involved in adipocyte regeneration, while CaHA-R did not affect these genes. Clinically, this could translate to healthy fat replacement with an enhanced effect beyond the improvement of the collagen structure and a longer-lasting effect with PLLA-SCA. Furthermore, the adipokines that appear to be upregulated are regenerative with a positive impact on skin health. PLLA-SCA has a novel and unique signature, which supports a potential regenerative mechanism of action through its role in the modulation of adipocyte function.

Enhancing the Stereocomplex Crystallization of PLLA/PDLA Symmetric Blend by Controlling the Degree of Molecular Chain Entanglement

In order to enhance the content of stereocomplex crystals (SC) in poly L-lactic acid (PLLA)/poly D-lactic acid (PDLA) symmetric blend, thereby improving the defects of low crystallinity and poor heat resistance of polylactic acid (PLA)-based materials, the samples with different entanglement degrees were prepared by freezing extration method. The critical overlap concentration of the blend system was quantitatively obtained using an Ubbelohde viscometer. Based on this concentration, samples with a series of concentration gradient were prepared to control the different degrees of molecular chain entanglement inside. The results indicated that the chain disentanglement could greatly increase the content of SC in the blend, whether in the precipitation crystallization or the melt crystallization process. Especially after the isothermal crystallization for 30min at 130oC, the L/D-0.1 sample with the highest degree of disentanglement almost only formed SC, accounting for 95.2% of the total crystallinity. Samples with lower entanglement degree had more crystal nuclei and faster growth rate of formed spherulites. For completely entangled sample L/D-50, the crystal nucleus of homo-crystalls (HC) could be considered as SC. Besides, the Vicat softening temperature (VST) of L/D-0.1 sample increased from 79.9oC of L/D-50 sample to 103.8oC with an obvious increase of 24.9oC. All these results provide new ideas for improving the performance of PLA-based materials and show promising development prospects of green and sustainable polymers.

Foreign-body granuloma formation in the lower eyelid after injection of poly-D,L-lactic acid as a collagen stimulator: a case report

Poly-D,L-lactic acid (PDLLA) is widely used in facial rejuvenation as a collagen stimulator, with a lower risk of granuloma formation compared to poly-L-lactic acid (PLLA). However, granulomas may still occur. In this case, a 58-year-old woman developed firm, non-tender, bilateral infraorbital granulomas 2 months after her third PDLLA injection for infraorbital hollowing. The lesions were unresponsive to intralesional trichloroacetic acid (TCA) and intense pulsed light therapy, necessitating surgical removal. Histopathological analysis confirmed foreign-body granulomas caused by the PDLLA filler. This case highlights the need for caution when injecting PDLLA into thin-skinned areas like the infraorbital region, where granulomas can be more visible due to limited tissue volume. Although PDLLA fillers are generally safe, granuloma formation remains a potential complication. Early diagnosis and treatment with non-surgical methods, such as intralesional TCA, should be prioritized. If these methods fail, surgical excision, aimed at preserving as much normal tissue as possible, may be necessary for optimal outcomes.

4-year follow-up results of percutaneous closure of atrial septal defect with the total biodegradable poly-L-lactic acid device: date from a prospective, single-center trial

Abstract Background The poly-L-lactic acid (PLLA) device is a novel, total biodegradable occluder dedicated to percutaneous closure of atrial septal defect (ASD) .Closure of ASD with the PLLA device has proven to be relatively safe and effective in our preclinical and first-in-human studies. Objective The aim of the study was to evaluate long-term safety and efficacy of the PLLA device in percutaneous closure of ASD in a large cohort of patients. Methods A prospective study enrolling patients who had a clinically significant ASD was conducted in our institution from May 2018 to August 2019. Percutaneous ASD closure was undertaken with the PLLA device. Evaluations were scheduled pre-hospital discharge and again at 1, 3, 6, 12, 24, 36 and 48 months post implantation. Primary endpoints were a composite of clinical success, including closure success and no major complications at the 48-month follow-up evaluation. Results A total of 52 patients (35 children, 55.8% females, median age 7.55 years, median weight 28.75Kg) underwent an attempt at percutaneous ASD closure with PLLA device. Successful device implantation was achieved in 50 (96.1%) of 52 patients with delivery attempts. All the 50 patients (100%) completed 4-year follow-up visit. Closure success at 4-year follow-up were 84% (42/50), with 8 patient (16%) reported to have clinically significant leaks, including 2 large residual leaks, 5 moderate residual leaks, and 1 small residual leak. 10 complications occurred, with 1 event of cardiac arrhythmia during procedure, and 9 follow-up events, consisting in cardiac arrhythmias (n=6), moderate or large mitral regurgitation (n=2), and headache (n=1). Conclusion Percutaneous ASD closure with PLLA device in human seems to be safe. However, increased occurrence of residual leaks overtime indicated that long-term efficacy of PLLA device in human was sub-optimal.TTE follow-up of a case with PLLA device

Safety and efficacy of Mg-Dy membrane with poly-L-lactic acid coating for guided bone regeneration

The aim of this study was to evaluate safety and efficacy of a poly-L-lactic acid (PLLA)-coated magnesium (Mg)-Dysprosium (Dy) membrane in guided bone regeneration (GBR) using a rabbit calvarium model. The microstructure of the Mg-Dy membrane surface and thickness of the PLLA coating were examined. In vitro degradation and cytotoxicity test was conducted. The in vivo study used 24 white male rabbits with two 8 mm-diameter defects created on the calvaria; 12 defects were randomly assigned per group: (1) Negative control, (2) positive control, (3) uncoated Mg, and (4) PLLA-coated Mg group. Specimens were harvested at 4, 8, and 12 weeks postoperatively for radiological, histological, and histomorphometric analyses. The PLLA-coated Mg-Dy membrane showed a low degree of degradation, indicating that the coating exerted a protective effect. In the cytotoxicity test, no deformed or degenerated cells were observed. In the in vivo study, radiographic and histomorphometric analyses indicated favorable new bone formation and maintenance of the graft material for PLLA-coated Mg group. PLLA-coated Mg group, compared to the uncoated counterpart, restored the bony contour more completely, without inducing significant inflammatory response. Our results support the safety and efficacy of PLLA-coated Mg-Dy membranes for GBR both in vitro and in vivo.

Multicentric Retrospective Study on Safety and Efficacy of a Novel Injectable Poly-l-Lactic Acid for Buttocks Recontouring.

Poly-l-lactic acid (PLLA) injectables have gained increasing attention in aesthetic medicine due to their biocompatibility and long-lasting effects. Although their primary application centers around facial rejuvenation, their potential for off-label use in other body areas has been investigated, demonstrating promising outcomes in terms of both efficacy and safety. This study aims to assess the safety and efficacy of a novel 630 mg PLLA-based filler (GANA X), in buttocks treatment. Six physicians treated 51 patients for buttock aesthetic treatment across six different medical facilities in Italy. A survey was filled by both physicians and patients regarding treatment safety, efficacy, and change in quality of life. We reported minor or mild adverse events, self-resolving within the next few days. Both physicians and patients confirmed notable aesthetic improvements following treatment, varying from moderate to significant enhancement. These effects endured throughout follow-up visits spanning up to 24 months. Patient-reported outcomes indicated elevated self-esteem and improved quality of life posttreatment. The high level of satisfaction reported by both physicians and patients highlights the efficacy and tolerability of GANA X filler for buttocks treatment, encouraging their use and research for off-label body areas.

A comparative invitro study of distinct and novel stent geometries on mechanical performances of poly-L-lactic acid cardiovascular stents.

Poly-L-lactic acid (PLLA) is one of the representative polymeric materials serving as bioresorbable stents (BRS) for cardiovascular disease due to its proper biodegradation, high biocompatibility, and adequate mechanical properties among polymer candidates for BRS. However, PLLA BRS as cardiovascular stents also have limitations because their mechanical properties including low radial strength and high elastic recoil are inferior to those of metallic-based BRS stents. In the study, we developed and manufactured distinct and novel types of stent geometries for investigating mechanical properties of thin-walled PLLA BRS (110 μm) for cardiovascular applications. Five key mechanical tests, including radial strength, crimping profile, flexibility, elastic recoil, and foreshortening were performed through a comprehensive analysis. In addition, we applied the finite element method for further validation and insight of mechanical behaviors of the PLLA BRS. Results revealed that Model 2 had advantages in high flexibility as well as radial strengths, which would be a proper option for complex and acutely curved lesions. Model 3 would be an optimum selection for stent placement in mild target site due to its strength in minimum elastic recoil. Even though Model 4 showed the highest radial strength, finite element simulation showed that the geometry caused higher maximum stress than that of Model 2 and Model 3 during the crimping process. Model 1 showed the most vulnerable geometry among the tested models in both invitro and finite element analysis. Such data may suggest potential guidance in regard to understanding the mechanical behaviors of PLLA BRS as not only applicable cardiovascular but also peripheral and intracranial stents.

Comparison of Different Types of Poly-L-lactic Acid Microspheres In Vitro and In Vivo Studies

Abstract Background Biodegradable polymers are commonly used as dermal fillers in plastic surgery. Among these, poly-L-lactic acid (PLLA) distinguishes itself owing to its good biocompatibility, degradability, and ability to act as a collagen stimulator. Objectives In this study, the differential behavior of PLLA microspheres with varying microscopic morphology and surface hydrophilicity was investigated both in vitro and in vivo. Methods The introduction of short hydrophilic polyethylene glycol (PEG) chains into the PLLA molecule was employed to modify the morphology and enhance the surface hydrophilicity of the microspheres. The morphology and physicochemical properties of the PLLA and PLLA-b-PEG microspheres were characterized. Irregular PLLA particles, PLLA and PLLA-b-PEG microspheres were implanted into the subcutaneous tissue of rabbit models, and at 4, 26 and 52 weeks after implantation, biopsy samples were collected for hematoxylin and eosin (H&amp;E) and Masson's trichrome staining to evaluate differences in the tissue response between different implants. Results The results of in vitro research demonstrated that while the addition of short-chain hydrophilic PEG afforded a smoother surface for the microspheres, it had no significant effect on the molecular weight and degradation rate of PLLA. The histological examination revealed that the PLLA-b-PEG microspheres exhibited enhanced biocompatibility compared to the pure PLLA microspheres, while the irregular PLLA particles showed the highest inflammatory response among the three materials. Conclusions In this study, we found that the properties of PLLA were improved upon modification by short-chain PEG without reducing the collagen regeneration ability, thereby affording a better histocompatibility.

A biodegradable piezoelectric scaffold promotes spinal cord injury nerve regeneration

Neural repair and regeneration remain one of the greatest challenges in regenerative medicine. The incorporation of intelligent scaffolds with noninvasive in vivo electrical stimulation illustrates considerable potential for tissue repair and regeneration. Nevertheless, the development of biomaterials that possess both biodegradable tissue scaffolds and electrical stimulation capabilities at a high level remains a significant obstacle. In this study, we effectively integrated the organic piezoelectric material poly-L-lactic acid (PLLA) with inorganic piezoelectric nanowires (potassium sodium niobate coated with polydopamine, KNN@PDA) to fabricate PLLA/KNN@PDA piezoelectric composite fibers. These fibers exhibit in-situ electrical stimulation capabilities, rendering them suitable for direct application in living tissues. The PLLA/KNN@PDA piezoelectric composite fibers not only function as biodegradable scaffolds for regenerative tissue engineering and platforms for in-situ electrical stimulation to enhance dorsal root ganglion axon growth, proliferation, and neuronal differentiation but also serve as versatile scaffolds for broader tissue engineering applications. In the complete spinal cord transection rat model, the piezoelectric scaffold enabled the recovery of rat motor function, indicating its significant ability to promote tissue formation and regeneration. Therefore, combining biodegradable piezoelectric tissue scaffolds with in situ electrical stimulation has significant therapeutic advantages for spinal cord injury repair and may be extended to other damaged tissues regeneration.

Non-enzymatic cholesterol biosensor: Electrochemical sensing based on peptide-polylactic acid thin film

Cholesterol is a fundamental lipid prevalent in eukaryotic cell membranes and circulating in the bloodstream bound to lipoproteins. It serves as a precursor to steroid hormones and is regarded as a biomarker for cardiovascular disease and other metabolic disorders. Numerous cholesterol detection methods predominantly rely on enzymes, which suffer from instability, leading to non-cost-effective biosensors with low sensitivity and poor reusability. Therefore, monitoring cholesterol levels with a feasible, rapid, and stable biosensor is critical for diagnosing and treating various disorders. This study aimed to develop a non-enzymatic cholesterol biosensor based on a selected cholesterol recognition peptide as the detection element. Screen-printed carbon electrodes (SPEs) modified with biocompatible poly-L-lactic acid (PLLA) porous nanomembranes (NMs) were utilized as support for the covalent immobilization of the peptide. Data obtained from electrochemical impedance spectroscopy (EIS) demonstrated the peptide's effective binding affinity towards cholesterol, paving the way for its implementation. The determination of cholesterol with the proposed biosensor exhibited a low limit of detection of 6.31 μM with linear responses ranging from 2–15 μM and 20–40 μM. These findings present an alternative method for cholesterol sensing by integrating novel peptides as biorecognition motifs with biocompatible polymeric materials, potentially useful as biocompatible and future point-of-care sensors.

Animal Experimental Study of Bioabsorbable Left Atrial Appendage Occluder.

Left atrial appendage (LAA) closure can prevent stroke in high-risk patients with atrial fibrillation.A bioabsorbable LAA occluder made of degradable polymer materials, such as polydioxanone (PDO) and poly-L-lactic acid (PLA), and nitinol wire was used. Occluders were successfully implanted in 18 Chinese rural dogs, 2 of which died within 48 hours after operation due to pericardial tamponade and hemorrhage, respectively. Follow-up observation was performed after transcatheter LAA closure. New tissue was found on the surface of the occluder 2 months after operation. No adjacent structures such as the mitral valve and the left superior pulmonary vein were affected by the occluder discs. Hematoxylin and eosin (HE) staining was performed at 3 months after operation, which showed intact intimal structure on the occluder surface, and unabsorbed PDO and PLA were observed. Scanning electron microscopy showed irregular arrangement of endothelial cells. New endothelial tissue was observed to completely cover the occluder at 6 months after operation. Most PDOs were replaced by fibrous connective tissue, and scanning electron microscopy showed regularly arranged endothelial cells. Pathological examination at 12 months showed only a small remnant of PDO. The gross specimens of the liver, spleen, and kidneys and pathological examination did not indicate thromboembolism.The bioabsorbable LAA occluder made of PDO, PLA, and nitinol wire was safe and effective for the occlusion of LAA in dogs. The surface of the occluder was endothelialized half a year after operation. The absorbable materials of the occluder were degraded after 1 year.

Poly-L-lactic acid in the correction of age-related changes in facial skin

Age-related changes in the skin of the face and neck are the result of a number of interrelated biochemical processes occurring in various tissues (dermis and epidermis, subcutaneous fat, musculoskeletal apparatus and bone tissue). Currently, there are a number of minimally invasive techniques to correct age-related changes in the skin of the face, but the discussion regarding the clinical efficacy and duration of retention of the effect in correcting age-related facial changes continues. Poly-L-lactic acid (PLLA) is popular with specialists and is used as an effective method of correcting involutive changes in the skin of the face, however, despite the extensive experience of its use, there is not enough research in foreign and domestic literature to study the duration of retention of the effect of drugs based on poly-L-lactic acid. The article presents an analysis of the data of modern literature devoted to the study of the effectiveness of the use of poly-L-lactic acid as a method of correcting age-related changes in the skin of the face.

Multimaterial additive manufacturing of poly-L-lactic acid– hydroxylapatite/graphene oxide scaffold fabricated via vat photopolymerization: experimental investigation, analysis and cell study

PurposeThis study aims to design and implement a multimaterial system for printing multifunctional specimens suitable for various sectors, with a particular focus on biomedical applications such as addressing mandibular bone loss.Design/methodology/approachTo enhance both the mechanical and biological properties of scaffolds, an automatic multimaterial setup using vat photopolymerization was developed. This setup features a linear system with two resin vats and one ultrasonic cleaning tank, facilitating the integration of diverse materials and structures to optimize scaffold composition. Such versatility allows for the simultaneous achievement of various characteristics in scaffold design.FindingsThe printed multimaterial scaffolds, featuring 20 Wt.% hydroxylapatite (HA) on the interior and poly-L-lactic acid (PLLA) with 1 Wt.% graphene oxide (GO) on the exterior, exhibited favorable mechanical and biological properties at the optimum postcuring and heat-treatment time. Using an edited triply periodic minimal surface (TPMS) lattice structure further enhanced these properties. Various multimaterial specimens were successfully printed and evaluated, showcasing the capability of the setup to ensure functionality, cleanliness and adequate interface bonding. Additionally, a novel Gyroid TPMS scaffold with a nominal porosity of 50% was developed and experimentally validated.Originality/valueThis study demonstrates the successful fabrication of multimaterial components with minimal contaminations and suitable mechanical and biological properties. By combining PLLA-HA and PLLA-GO, this innovative technique holds significant promise for enhancing the effectiveness of regenerative procedures, particularly in the realm of dentistry.

Construction of a Curcumin‐Loaded PLLA/PCL Micro‐Nano Conjugated Fibrous Membrane to Synergistically Prevent Postoperative Adhesion From Multiple Perspectives

AbstractPostoperative adhesion (POA) has emerged as a prevalent clinical challenge in soft tissue repair, emphasizing the critical need for preventive measures. However, the complex POA development process makes POA prevention from a single aspect insufficient. Hence, a curcumin‐loaded poly‐L‐lactic acid‐poly (caprolactone) micro‐nano conjugated fibrous membrane (PAPC MCFM (cur)) is engineered to synergistically prevent POA from multiple perspectives, in which poly (caprolactone) (PCL) nanofibers (118 ± 12 nm) with low orientation traverse the oriented poly‐L‐lactic acid (PLLA) microfibers (2.0 ± 0.3 µm). The PAPC MCFM not only significantly improves the mechanical properties of the anisotropic fibrous membrane (AIFM) that the modulus of elasticity and the tensile strength in the direction vertical to microfiber orientation increase by 4.5 and 13.0 times, respectively, but also can further enhance the “contact guidance effect” of AIFM, i.e., hindering fibroblast adhesion, proliferation, and differentiation to myofibroblast through inhibiting integrin β1 activation, vinculin expression and focal adhesion (FA) formation, and the nuclear localization activation of yes‐associated protein (YAP). Except for these effects, PAPC MCFM loading with 2.5 mg mL−1 curcumin can further prevent POA by delivering anti‐inflammatory, antioxidant, and antibacterial properties, and by suppressing fibrosis through decreased transforming growth factor‐β1(TGF‐β1) expression, showing effective POA prevention in rat abdominal cavity and rabbit dura mater models.

MXene-coated piezoelectric poly-L-lactic acid membrane accelerates wound healing by biomimicking low-voltage electrical pulses

Electrical stimulation therapy is effective in promoting wound healing by rescuing the decreased endogenous electrical field, where self-powered and miniaturized devices such as nanogenerators become the emerging trends. While high-voltage and unidirectional electric field may pose thermal effect and damage to the skin, nanogenerators with lower voltages, pulsed or bidirectional currents, and less invasive electrodes are preferred. Herein, we construct a polydopamine (PDA)-modified poly-L-lactic acid (PLLA) /MXene (PDMP/MXene) nanofibrous composite membrane that generates piezoelectric voltages matching the transepithelial potential (TEP) to accelerate wound healing. PDA coating not only enhances the piezoelectricity of PLLA by dipole attraction and alignment, but also increases its hydrophilicity and facilitates subsequent MXene adhesion for electrical conductivity and stability in physiological environment. When applied as wound dressings in mice, the PDMP/MXene membranes act as a nanogenerators with reduced internal resistances and satisfactory piezoelectric performances that resemble bioelectric potentials (~10 mV) responding to physical activities. The membrane significantly accelerates wound closure by facilitating fibroblast migration, collagen deposition and angiogenesis, and suppressing the expression of inflammatory responses. This piezoelectric fibrous membrane therefore provides a convenient solution for speeding up wound healing by sustained low voltage mimicking bioelectricity, better cell affinity.

Melatonin-coated nanofiber cell sheets promote periodontal regeneration through ROS scavenging and preservation of stemness

Mesenchymal stem cell (MSC)-based cell sheet engineering holds great promise for periodontal tissue engineering and restoring damaged tissues. However, achieving optimal regenerative outcomes remains a challenge. This study introduces a novel approach that integrates melatonin-coated nanofiber fragments (mNFs) into dental follicle stem cell sheets (mNF-CSs) to enhance their regenerative potential. The mNF-CSs were engineered using electrospun poly-L-lactic acid (PLLA) nanofiber sheets fragmented into mNFs and coated with melatonin, a potent antioxidant and osteogenic agent. The mNF-CSs exhibited a homogenous morphology with sustained melatonin release over 21 days, providing a prolonged antioxidative effect critical for tissue regeneration. In vitro experiments demonstrated that mNF-CSs significantly reduced intracellular reactive oxygen species (ROS) levels and upregulated antioxidative proteins such as SOD1 and SOD2, resulting in improved cell viability, maintenance of stemness, and enhanced osteogenic differentiation potential of dental follicle stem cells (DFCs). In vivo studies using both a nude mouse and a rat periodontal defect model demonstrated that mNF-CSs promoted alveolar bone repair and periodontal tissue regeneration, with enhanced retention of MSCs at the defect site and increased expression of periodontal tissue-related markers. Transcriptome analysis revealed the upregulation of genes associated with biomineralization, odontogenesis, and autophagy pathways in mNF-CSs, suggesting their ability to modulate crucial cellular processes for tissue regeneration. Overall, mNF-CSs offer a promising strategy for enhancing periodontal tissue engineering applications, providing a platform for improving bone grafts and regenerative medicine strategies in the context of periodontal diseases.

Piezoelectric Biomedical Material, Poly-L-Lactic Acid (PLLA), in the Treatment of Spinal Epidural Compression: Diagnosis, Monitoring, and Postoperative Support

This study aims to design an intelligent biomedical piezoelectric material for monitoring the pressure in the spinal epidural space caused by postoperative hematoma compression (spinal epidural hematoma). Hematoma compression in the spinal epidural space is a clinically challenging condition that is difficult to diagnose, and failure to address it within forty-eight hours may lead to severe consequences. Given its urgency, prompt and accurate diagnosis and intervention are crucial. Due to its elusive diagnostic nature, patients often miss the opportune time for treatment. Therefore, this study utilizes poly L-lactic acid (PLLA), an FDA-approved highly biocompatible biomaterial. After undergoing high-pressure polarization, PLLA exhibits excellent piezoelectric properties, making it an ideal material for monitoring intracavitary pressure. Additionally, since postoperative hematoma formation is a primary cause of spinal epidural membrane compression, this study integrates urokinase, a potent thrombolytic protein, with PLLA electrospun fibers, enabling preliminary treatment upon pressure detection.This intelligent organic biomedical material not only enables real-time monitoring of postoperative spinal epidural space pressure but also passively utilizes ultrasound to release urokinase from PLLA fibers for initial treatment when pressure is detected. Furthermore, the application of electrospun PLLA biomedical material makes the material more easily moldable and simplifies the manufacturing process, expanding its potential applications. In summary, this technology combines expertise in organic materials science, electrochemistry, and clinical medicine, offering an innovative approach to addressing the crisis posed by hematoma compression in the spinal epidural space. In future clinical applications, this technology holds the promise of providing earlier and more effective treatment for patients, potentially becoming a significant breakthrough in the fields of medical electronics and biomedical engineering. Keywords: Piezoelectric Biomaterial, Pressure Monitoring Sensor, Drug Control Release, Postoperative Support, Diagnostic Innovation

An In Vitro Model of the Blood-Brain Barrier for the Investigation and Isolation of the Key Drivers of Barriergenesis.

The blood-brain barrier (BBB) tightly regulates substance transport between the bloodstream and the brain. Models for the study of the physiological processes affecting the BBB, as well as predicting the permeability of therapeutic substances for neurological and neurovascular pathologies, are highly desirable. Existing models, such as Transwell utilizing-models, do not mimic the extracellular environment of the BBB with their stiff, semipermeable, non-biodegradable membranes. To help overcome this, we engineered electrospun membranes from poly L-lactic acid in combination with a nanometric coating of poly(ethyl acrylate) (PEA) that drives fibrillogenesis of fibronectin, facilitating the synergistic presentation of both growth factors and integrin binding sites. Compared to commercial semi-porous membranes, these membranes significantly improve the expression of BBB-related proteins in brain endothelial cells. PEA-coated membranes in combination with different growth factors and extracellular protein coatings reveal nerve growth factor (NGF) and fibroblast growth factor (FGF-2) caused formation of better barriers in vitro. This BBB model offers a robust platform for studying key biochemical factors influencing barrier formation that marries the simplicity of the Transwell model with the highly tunable electrospun PEA-fibronectin membranes. This enables the generation of high-throughput drug permeability models without the need of complicated co-culture conditions.

Lactate triggers KAT8-mediated LTBP1 lactylation at lysine 752 to promote skin rejuvenation by inducing collagen synthesis in fibroblasts

Decreased collagen synthesis by fibroblasts is a key aspect of skin aging. Poly-L-Lactic Acid (PLLA) is a bioabsorbable material that can release lactate continuously, stimulating endogenous collagen synthesis in the skin. Herein, this study aimed to investigate the impact of PLLA-released lactate on collagen production in fibroblasts for skin rejuvenation. Human fibroblasts were exposed to varying concentrations of PLLA in vitro, while PLLA was injected into the back skin of aged mice in vivo. Safety and efficacy of PLLA on collagen synthesis and skin rejuvenation were evaluated through Calcein-AM/PI staining, EdU proliferation assay, and analysis of collagen I and collagen III expression in fibroblasts using western blotting and immunofluorescence. To elucidate the underlying mechanisms, lactate contents in cell-free supernatant and cell lysates from PLLA-treated fibroblasts, as well as total lysine lactylation (Pan Kla) levels were measured. Additionally, we found that fibroblasts can uptake extracellular lactate released from PLLA through monocarboxylate transporter-1 (MCT1) to facilitate latent-transforming growth factor beta-binding protein 1 (LTBP1) lactylation at lysine 752 (K752) via a KAT8-dependent mechanism, then increases the protein levels of collagen I and collagen III in fibroblasts. Overall, this study highlights a valuable insight into lactylation modification of non-histone protein for skin rejuvenation.

Polydopamine-modified biochar supported polylactic acid and zero-valent iron affects the functional microbial community structure for 1,1,1-trichloroethane removal in simulated groundwater

In-situ enhanced bioreduction by functional materials is a cost-effective technology to remove chlorinated hydrocarbons in groundwater. Herein, a novel polydopamine (PDA)-modified biochar (BC)-based composite containing nanoscale zero-valent iron (nZVI) and poly-l-lactic acid (PLLA) (PB-PDA-Fe) was synthesized to enhance the removal of 1,1,1-trichloroethane (1,1,1-TCA) in simulated groundwater with actual site sediments. Its impact on functional microbial community structure in system was also investigated. The typical characterizations revealed uniform dispersion of PLA and nZVI particles on the BC surface, being smoother after PDA coating. The composite exhibited a significantly higher performance on 1,1,1-TCA removal (82.38%, initial concentration 100 mg/L) than Fe-PDA and PB-PDA treatments. The diversity and richness of the microbial community in the composite treatment consistently decreased during incubation due to a synergistic effect between PLLA-BC and nZVI. Desulfitobaterium, Pedobacter, Sphaerochaeta, Shewanella, and Clostridium were identified as enriched genera by the composite through DNA-stable isotope probing (DNA-SIP), playing a crucial role in the bioreductive dechlorination process. All the above results demonstrate that this novel composite selectively enhances the activity of microorganisms with extracellular respiration functions to efficiently dechlorinate 1,1,1-TCA. These findings could contribute to understanding the responsive microbial community by carbon-iron composites and expedite the application of in-situ enhanced bioreduction for effective remediation of chlorinated hydrocarbon-contaminated groundwater.