Complications of collagen biostimulators in Brazil: Description of products, treatments, and evolution of 55 cases.

BACKGROUND: Complications of temporary and permanent fillers have been extensively studied. However, there is a lack of comparative data regarding poly-L-lactic acid (PLLA), calcium hydroxyapatite (CaHA), and polycaprolactone (PCL) known as collagen biostimulators. AIMS: This study addressed the complications of collagen biostimulators concerning their diagnosis, type of product, treatment, and monitoring. PATIENTS/METHODS: An electronic questionnaire was sent to Brazilian dermatologic ultrasound experts to identify complications related to biostimulators. The type of biostimulator, location of application, number of vials injected, application plan, time between injection treatment and complication, injector profile, treatment, and prognosis were assessed. RESULTS: Fifty-five cases were identified, of which 49.1% were caused by PLLA-Elleva®, 23.6% by CaHA (alone or combined with hyaluronic acid), 20.0% by PLLA-Sculptra®, and 7.3% by PCL. The most affected area was the face (72.7%), with nodules being the most common clinical form (89.1%), generally occurring late (60.0%) (>1 month). Only one case was injected at an incorrect depth (musculoaponeurotic system-SMAS). Despite several treatments, including saline (45.5%), hyaluronidase (25.5%), diluted corticosteroids (23.6%), and energy-based devices (10.9%), only five cases showed complete resolution. Hyaluronidase was beneficial in complications related to fillers when there was an association of calcium hydroxyapatite with hyaluronic acid (p < 0.01). CONCLUSIONS: Complications from collagen biostimulators were more common on the face, typically manifesting about 1 month after treatment. These issues seemed to be related more to the properties of the products rather than inadequate technique. Furthermore, hyaluronidase demonstrated efficacy only in cases where there was an association with HA.

Development and characterization of ceramic-polymeric hybrid scaffolds for bone regeneration: incorporating of bioactive glass BG-58S into PDLLA matrix.

In recent years, there has been a notable surge of interest in hybrid materials within the biomedical field, particularly for applications in bone repair and regeneration. Ceramic-polymeric hybrid scaffolds have shown promising outcomes. This study aimed to synthesize bioactive glass (BG-58S) for integration into a bioresorbable polymeric matrix based on PDLLA, aiming to create a bioactive scaffold featuring stable pH levels. The synthesis involved a thermally induced phase separation process followed by lyophilization to ensure an appropriate porous structure. BG-58S characterization revealed vitreous, bioactive, and mesoporous structural properties. The scaffolds were analyzed for morphology, interconnectivity, chemical groups, porosity and pore size distribution, zeta potential, pH, in vitro degradation, as well as cell viability tests, total protein content and mineralization nodule production. The PDLLA scaffold displayed a homogeneous morphology with interconnected macropores, while the hybrid scaffold exhibited a heterogeneous morphology with smaller diameter pores due to BG-58S filling. The hybrid scaffold also demonstrated a pH buffering effect on the polymer surface. In addition to structural characteristics, degradation tests indicated that by incorporating BG-58S modified the acidic degradation of the polymer, allowing for increased total protein production and the formation of mineralization nodules, indicating a positive influence on cell culture.

Sonochemical Synthesis of Magnetite/Poly(lactic acid) Nanocomposites.

Nanocomposites based on poly(lactic acid) (PLA) and magnetite nanoparticles (MNP-Fe3O4) show promise for applications in biomedical treatments. One key challenge is to improve the stabilization and dispersion of MNP-Fe3O4. To address this, we synthesized MNP-Fe3O4/PLA nanocomposites using ultrasound mediation and a single iron(II) precursor, eliminating the need for surfactants or organic solvents, and conducted the process under ambient conditions. The resulting materials, containing 18 and 33 wt.% Fe3O4, exhibited unique thermal behavior characterized by two mass losses: one at a lower degradation temperature (Td) and another at a higher Td compared to pure PLA. This suggests that the interaction between PLA and MNP-Fe3O4 occurs through hydrogen bonds, enhancing the thermal stability of a portion of the polymer. Fourier Transform Infrared (FT-IR) analysis supported this finding, revealing shifts in bands related to the terminal -OH groups of the polymer and the Fe-O bonds, thereby confirming the interaction between the groups. Raman spectroscopy demonstrated that the PLA serves as a protective layer against the oxidation of MNP-Fe3O4 in the 18% MNP-Fe3O4/PLA nanocomposite when exposed to a high-power laser (90 mW). Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM) analyses confirmed that the synthetic procedure yields materials with dispersed nanoparticles within the PLA matrix without the need for additional reactants.

Targeted and Individualized Gluteal Poly-L-Lactic Acid Injection for Optimal Aesthetic Results in the Gluteal Region.

Objective: The robust safety and efficacy profile associated with the use of biodegradable fillers such as poly-L-lactic acid (PLLA) for facial rejuvenation has resulted in a growing interest in off-label use for various aesthetic applications, including gluteal augmentation. The authors describe a novel targeted and individualized technique of PLLA injection into the buttock region. Methods: The technique involves clinical and anatomical evaluations of the gluteal region, and there are three distinct approaches for injecting PLLA in the gluteal region based on the most important factor to be improved: (1) skin quality, (2) contour and lifting, or (3) projection and volume. Results: This novel technique is associated with favorable patient outcomes in terms of improvements across all key areas of gluteal augmentation; improvement in skin quality and laxity, contour improvement and lifting, and gluteal volume and projection. Since its initiation, this technique has been found to be both cost-effective and clinically efficacious, with demonstratable benefits achieved with a lower volume of PLLA compared to other PLLA injection techniques. Limitations: Assessment of patient outcomes with this technique have, to date, been subjective clinical observations, which does not include quantitative outcomes such as patient satisfaction data or safety outcomes. Conclusion: We describe an optimized and individualized approach for injecting the collagen biostimulator PLLA in the gluteal region according to the needs of each patient.

Clinical and histological comparative outcomes after injections of poly-L-lactic acid and calcium hydroxyapatite in arms: A split side study.

BACKGROUND: Although much has been published on the use of poly-L-lactic acid (PLLA) and calcium hydroxyapatite (CaHA) for off-face indications, questions remain regarding their exact mechanisms of action in subcutaneous tissue and their comparative efficacy. OBJECTIVE: To present the clinical and histological results of the PLLA and CaHA injections into the opposing arms of the same patients. METHODS: Five women received superficial subcutaneous injections of PLLA into the left arm and CaHA into the right arm. After three sessions, the clinical and histological outcomes were analyzed. RESULTS: After the first session, three patients showed improvement in the right arm (CaHA), but at the end of study, two patients showed better results in the left arm (PLLA). Histologically, moderate to intense lymphocytic and giant cell infiltrate, as well as collagen and elastic fiber neoformation, were observed equally near the particles of both products. Dermis had no inflammatory or fiber alterations. CONCLUSION: In this study, there were no clinical differences between these two fillers. Despite current thinking and previous histological studies, we found both products produced moderate to intense inflammatory reaction, as well as collagenic/elastogenic fiber neoformation, only in the subcutaneous tissue of the immediate vicinity and surrounding the individual filler particles.

Changes in Facial Morphology Using Poly-L-lactic Acid Application According to Vector Technique: A Case Series.

Background: The search for nonsurgical cosmetic procedures has increased considerably in recent years. A new injection technique, using vector direction, has shown good results in improving facial aesthetics but to date has only been performed with hyaluronic acid which can be associated with a risk of vascular complications. Therefore, in clinical practice, it would be interesting to assess this technique with a liquid product already widely used in the facial region, and at the same time bring the same aesthetic benefits, but with greater durability than hyaluronic acid. Objective: To investigate the improvement of facial morphology in patients with facial flaccidity submitted to the vector technique using poly-L-lactic acid (PLLA) (Sculptra®; Galderma, Lausanne, Switzerland). Case Series: Here we report the outcomes of three cases of female patients, aged between 41 and 55 years, seeking improvement of facial flaccidity. In each patient, PLLA was applied in the posterior temporal region as a bolus, in three points, with a 2-mL injection in the upper region, 1.5mL in the midpoint, and 1.5mL at the bottom point. Each of the three patients showed an improvement in face morphology, with concomitant improvement in the support and stretching of the face and improvement in skin sagging in the upper, middle, and bottom regions. Conclusion: The vector technique with PLLA is a viable alternative for the treatment of patients with facial skin flaccidity, providing harmonious and progressive improvement in the face morphology.

Polymers Based on PLA from Synthesis Using D,L-Lactic Acid (or Racemic Lactide) and Some Biomedical Applications: A Short Review.

Poly(lactic acid) (PLA) is an important polymer that is based on renewable biomass resources. Because of environmental issues, more renewable sources for polymers synthesis have been sought for industrial purposes. In this sense, cheaper monomers should be used to facilitate better utilization of less valuable chemicals and therefore granting more sustainable processes. Some points are raised about the need to study the total degradability of any PLA, which may require specific composting conditions (e.g., temperature, type of microorganism, adequate humidity and aerobic environment). Polymerization processes to produce PLA are presented with an emphasis on D,L-lactic acid (or rac-lactide) as the reactant monomer. The syntheses involving homogeneous and heterogeneous catalytic processes to produce poly(D,L-Lactic acid) (PDLLA) are also addressed. Additionally, the production of blends, copolymers, and composites with PDLLA are also presented exemplifying different preparation methods. Some general applications of these materials mostly dedicated to the biomedical area over the last 10-15 years will be pointed out.

Poly(L-co-D,L lactic acid-co-Trimethylene Carbonate) 3D printed scaffold cultivated with mesenchymal stem cells directed to bone reconstruction: In vitro and in vivo studies.

A recent and quite promising technique for bone tissue engineering is the 3D printing, peculiarly regarding the production of high-quality scaffolds. The 3D printed scaffold strictly provides suitable characteristics for living cells, in order to induce treatment, reconstruction and substitution of injured tissue. The purpose of this work was to evaluate the behavior of the 3D scaffold based on Poly(L-co-D,L lactic acid-co-Trimethylene Carbonate) (PLDLA-TMC), which was designed in Solidworks™ software, projected in 3D Slicer™, 3D printed in filament extrusion, cultured with mesenchymal stem cells (MSCs) and tested in vitro and in vivo models. For in vitro study, the MSCs were seeded in a PLDLA-TMC 3D scaffold with 600 µm pore size and submitted to proliferation and osteogenic differentiation. The in vivo assays implanted the PLDLA-TMC scaffolds with or without MSCs in the calvaria of Wistar rats submitted to 8 mm cranial bone defect, in periods of 8-12 weeks. The results showed that PLDLA-TMC 3D scaffolds favored adherence and cell growth, and suggests an osteoinductive activity, which means that the material itself augmented cellular differentiation. The implanted PLDLA-TMC containing MSCs, showed better results after 12 weeks prior grafting, due the absence of inflammatory processes, enlarged regeneration of bone tissue and facilitated angiogenesis. Notwithstanding, the 3D PLDLA-TMC itself implanted enriched tissue repair; the addition of cells known to upregulate tissue healing reinforce the perspectives for the PLDLA-TMC applications in the field of bone tissue engineering in clinical trials.

Biological Characterization of Polymeric Matrix and Graphene Oxide Biocomposites Filaments for Biomedical Implant Applications: A Preliminary Report.

Carbon nanostructures application, such as graphene (Gr) and graphene oxide (GO), provides suitable efforts for new material acquirement in biomedical areas. By aiming to combine the unique physicochemical properties of GO to Poly L-lactic acid (PLLA), PLLA-GO filaments were produced and characterized by X-ray diffraction (XRD). The in vivo biocompatibility of these nanocomposites was performed by subcutaneous and intramuscular implantation in adult Wistar rats. Evaluation of the implantation inflammatory response (21 days) and mesenchymal stem cells (MSCs) with PLLA-GO took place in culture for 7 days. Through XRD, new crystallographic planes were formed by mixing GO with PLLA (PLLA-GO). Using macroscopic analysis, GO implanted in the subcutaneous region showed particles' organization, forming a structure similar to a ribbon, without tissue invasion. Histologically, no tissue architecture changes were observed, and PLLA-GO cell adhesion was demonstrated by scanning electron microscopy (SEM). Finally, PLLA-GO nanocomposites showed promising results due to the in vivo biocompatibility test, which demonstrated effective integration and absence of inflammation after 21 days of implantation. These results indicate the future use of PLLA-GO nanocomposites as a new effort for tissue engineering (TE) application, although further analysis is required to evaluate their proliferative capacity and viability.

Aspirin-Loaded Polymeric Films for Drug Delivery Systems: Comparison between Soaking and Supercritical CO2 Impregnation.

Polymeric implants loaded with drugs can overcome the disadvantages of oral or injection drug administration and deliver the drug locally. Several methods can load drugs into polymers. Herein, soaking and supercritical CO2 (scCO2) impregnation methods were employed to load aspirin into poly(l-lactic acid) (PLLA) and linear low-density polyethylene (LLDPE). Higher drug loadings (DL) were achieved with scCO2 impregnation compared to soaking and in a shorter time (3.4 ± 0.8 vs. 1.3 ± 0.4% for PLLA; and 0.4 ± 0.5 vs. 0.6 ± 0.5% for LLDPE), due to the higher swelling capacity of CO2. The higher affinity of aspirin explained the higher DL in PLLA than in LLDPE. Residual solvent was detected in LLDPE prepared by soaking, but within the FDA concentration limits. The solvents used in both methods acted as plasticizers and increased PLLA crystallinity. PLLA impregnated with aspirin exhibited faster hydrolysis in vitro due to the catalytic effect of aspirin. Finally, PLLA impregnated by soaking showed a burst release because of aspirin crystals on the PLLA surface, and released 100% of aspirin within 60 days, whereas the PLLA prepared with scCO2 released 60% after 74 days by diffusion and PLLA erosion. Hence, the scCO2 impregnation method is adequate for higher aspirin loadings and prolonged drug release.

Safety in immediate reconstitution of poly-l-lactic acid for facial biostimulation treatment.

Poly-L-lactic acid is presented as freeze-dried preparation of 150 mg per vial and, according to consensus, the recommendation on your preparation is hydrate in sterile water for injection (SWFI) or bacteriostatic water at room temperature for ≥24 hours. (J Drugs Dermatol; 2014;13:s44) However, in these long periods of hydration, it is time-consuming and costly for the physicians. To demonstrate the safeness of immediate reconstitution of facial biostimulation treatment with PLLA. A clinical prospective study with 26 Latin American female patients, aged between 27 and 80 years, complaining of facial laxity of treated with immediate PLLA reconstitution. One PLLA vial was injected per session in 12 mL total dilution. All patients had their pictures taken before and after the treatment in Photo Analysis Program Vectra 3D (Canfield® ). A follow-up 90 days was performed. The total of 58 facial applications of PLLA was reported in female patients with a mean age 52.62 (±13.46) years. Pain was reported in 17 injections (29.31%) and ecchymosis in 6 (10.34%). Also, 2 patients (3.44%) developed a nodule. None of the patients presented significant bruising, edema, or papules formation. Despite the literature declare that a longer hydration times (up to 48 hours) have been shown to reduce the risk of nodule formation (Aesthet Surg J; 2011;31:95), our study demonstrated the safeness of injection with immediate reconstitution and a very low adverse events rate. Immediate PLLA reconstitution is a great asset for physicians, injections in account of being less laborious, less time-consuming, and reducing product loss for the injector.

Electroactive nanofibers mats based on poly(l-lactic acid)/poly(ortho-ethoxyaniline) blends for biological applications.

The combination of scaffolds with desirable topographic characteristics and the use of electrical stimulus consist of a strategy to repair and regenerate tissues. An interesting approach to obtain electroactive scaffolds with the aforementioned features comprises on the use of conducting polymers which can be blended with other biocompatible polymers. In this work, poly(l-lactic acid) (PLLA) and poly(ortho-ethoxyaniline) (POEA) were synthesized and PLLA/POEA mats were prepared for the first time by electrospinning technique. Topographic characterization of PLLA/POEA showed a tunable mean diameter of the nanofibers by changing the electrospinning parameters. The presence of POEA into the blend was confirmed by X-ray photoelectron and Fourier-transform infrared spectroscopy analyses. Differential scanning calorimetry curves of PLLA/POEA exhibited shift positions of Tc and absence of the exothermic peak related to the characteristic isomerization process of POEA at high temperatures. The thermal analysis results indicate a favored miscibility between the polymers which is likely resulted from the strong interaction between polymers functionalities. The homogenous distribution of POEA chains throughout the scaffold rendered redox reversibility property for the mats. Biocompatibility results showed non-cytotoxic features for PLLA/POEA, attesting this novel system as a promising candidate for biological applications.

Viability Assays of PLLA Fibrous Membranes Produced by Rotary Jet Spinning for Application in Tissue Engineering

Abstract Tissue engineering suggests different forms to reconstruct tissues and organs. One of the ways is through the use of polymeric biomaterials such as poly(L-lactic acid) (PLLA). PLLA is a recognized material in tissue engineering due to its characteristics as biocompatibility and bioresorbability. In this work PLLA fibrous membranes were produced by a simple technique known as rotary jet spinning. The rotary jet spinning consists of fibrous membranes production, with fibers of scale nano/micrometric, from a polymeric solution through the centrifugal force generated by the equipment. The membranes formed were subjected to preliminary in vitro assays to verify the cytotoxicity of the membranes made in contact with the cells. Direct cytotoxicity assays were performed through the MTT, AlamarBlue® and Live/Dead® tests, with fibroblastic and osteoblastic cells. The results obtained in this study showed that PLLA membranes produced by rotary jet spinning showed promising results in the 24-hours contact period of the cells with the PLLA fibrous membranes. The information presented in this preliminary study provides criteria to be taken in the future procedures that will be performed with the biomaterial produced, aiming at its improvement.

Effect of poly (l-lactic acid) scaffolds seeded with aligned diaphragmatic myoblasts overexpressing connexin-43 on infarct size and ventricular function in sheep with acute coronary occlusion.

Diaphragmatic myoblasts (DM) are stem cells of the diaphragm, a muscle displaying high resistance to stress and exhaustion. We hypothesized that DM modified to overexpress connexin-43 (cx43), seeded on aligned poly (l-lactic acid) (PLLA) sheets would decrease infarct size and improve ventricular function in sheep with acute myocardial infarction (AMI). Sheep with AMI received PLLA sheets without DM (PLLA group), sheets with DM (PLLA-DM group), sheets with DM overexpressing cx43 (PLLA-DMcx43) or no treatment (control group, n = 6 per group). Infarct size (cardiac magnetic resonance) decreased ∼25% in PLLA-DMcx43 [from 8.2 ± 0.6 ml (day 2) to 6.5 ± 0.7 ml (day 45), p < .01, ANOVA-Bonferroni] but not in the other groups. Ejection fraction (EF%) (echocardiography) at 3 days post-AMI fell significantly in all groups. At 45 days, PLLA-DM y PLLA-DMcx43 recovered their EF% to pre-AMI values (PLLA-DM: 61.1 ± 0.5% vs. 58.9 ± 3.3%, p = NS; PLLA-DMcx43: 64.6 ± 2.9% vs. 56.9 ± 2.4%, p = NS), but not in control (56.8 ± 2.0% vs. 43.8 ± 1.1%, p < .01) and PLLA (65.7 ± 2.1% vs. 56.6 ± 4.8%, p < .01). Capillary density was higher (p < .05) in PLLA-DMcx43 group than in the remaining groups. In conclusion, PLLA-DMcx43 reduces infarct size in sheep with AMI. PLLA-DMcx43 and PLLA-DM improve ventricular function similarly. Given its safety and feasibility, this novel approach may prove beneficial in the clinic.

Simvastatin and nanofibrous poly(l-lactic acid) scaffolds to promote the odontogenic potential of dental pulp cells in an inflammatory environment.

In this study, we investigated the anti-inflammatory, odontogenic and pro-angiogenic effects of integrating simvastatin and nanofibrous poly(l-lactic acid) (NF-PLLA) scaffolds on dental pulp cells (DPCs). Highly porous NF-PLLA scaffolds that mimic the nanofibrous architecture of extracellular matrix were first fabricated, then seeded with human DPCs and cultured with 0.1 µM simvastatin and/or 10 µg/mL pro-inflammatory stimulator lipopolysaccharide (LPS). The gene expression of pro-inflammatory mediators (TNF-α, IL-1ß and MMP-9 mRNA) and odontoblastic markers (ALP activity, calcium content, DSPP, DMP-1 and BMP-2 mRNA) were quantified after long-term culture in vitro. In addition, we evaluated the scaffold's pro-angiogenic potential after 24 h of in vitro co-culture with endothelial cells. Finally, we assessed the combined effects of simvastatin and NF-PLLA scaffolds in vivo using a subcutaneous implantation mouse model. The in vitro studies demonstrated that, compared with the DPC/NF-PLLA scaffold constructs cultured only with pro-inflammatory stimulator LPS, adding simvastatin significantly repress the expression of pro-inflammatory mediators. Treating LPS+ DPC/NF-PLLA constructs with simvastatin also reverted the negative effects of LPS on expression of odontoblastic markers in vitro and in vivo. Western blot analysis demonstrated that these effects were related to a reduction in NFkBp65 phosphorylation and up-regulation of PPARγ expression, as well as to increased phosphorylation of pERK1/2 and pSmad1, mediated by simvastatin on LPS-stimulated DPCs. The DPC/NF-PLLA constructs treated with LPS/simvastatin also led to an increase in vessel-like structures, correlated with increased VEGF expression in both DPSCs and endothelial cells. Therefore, the combination of low dosage simvastatin and NF-PLLA scaffolds appears to be a promising strategy for dentin regeneration with inflamed dental pulp tissue, by minimizing the inflammatory reaction and increasing the regenerative potential of resident stem cells. STATEMENT OF SIGNIFICANCE: The regeneration potential of stem cells is dependent on their microenvironment. In this study, we investigated the effect of the microenvironment of dental pulp stem cells (DPSCs), including 3D structure of a macroporous and nanofibrous scaffold, the inflammatory stimulus lipopolysaccharide (LPS) and a biological molecule simvastatin, on their regenerative potential of mineralized dentin tissue. The results demonstrated that LPS upregulated inflammatory mediators and suppressed the odontogenic potential of DPSCs. Known as a lipid-lowing agent, simvastatin was excitingly found to repress the expression of pro-inflammatory mediators, up-regulate odontoblastic markers, and exert a pro-angiogenic effect on endothelial cells, resulting in enhanced vascularization and mineralized dentin tissue regeneration in a biomimetic 3D tissue engineering scaffold. This novel finding is significant for the fields of stem cells, inflammation and dental tissue regeneration.

Aligned ovine diaphragmatic myoblasts overexpressing human connexin-43 seeded on poly (L-lactic acid) scaffolds for potential use in cardiac regeneration.

Diaphragmatic myoblasts (DMs) are precursors of type-1 muscle cells displaying high exhaustion threshold on account that they contract and relax 20 times/min over a lifespan, making them potentially useful in cardiac regeneration strategies. Besides, it has been shown that biomaterials for stem cell delivery improve cell retention and viability in the target organ. In the present study, we aimed at developing a novel approach based on the use of poly (L-lactic acid) (PLLA) scaffolds seeded with DMs overexpressing connexin-43 (cx43), a gap junction protein that promotes inter-cell connectivity. DMs isolated from ovine diaphragm biopsies were characterized by immunohistochemistry and ability to differentiate into myotubes (MTs) and transduced with a lentiviral vector encoding cx43. After confirming cx43 expression (RT-qPCR and Western blot) and its effect on inter-cell connectivity (fluorescence recovery after photobleaching), DMs were grown on fiber-aligned or random PLLA scaffolds. DMs were successfully isolated and characterized. Cx43 mRNA and protein were overexpressed and favored inter-cell connectivity. Alignment of the scaffold fibers not only aligned but also elongated the cells, increasing the contact surface between them. This novel approach is feasible and combines the advantages of bioresorbable scaffolds as delivery method and a cell type that on account of its features may be suitable for cardiac regeneration. Future studies on animal models of myocardial infarction are needed to establish its usefulness on scar reduction and cardiac function.

Development of a membrane of poly (L-co-D,L lactic acid-co-trimethylene carbonate) with aloe vera: An alternative biomaterial designed to improve skin healing.

The search for new therapies and drugs that act as topical agents to relieve pain and control the infectious processes in burns always attracted interest in clinical trials. As an alternative to synthetic drugs, the use of natural extracts is useful in the development of new strategies and formulations for improving the life quality. The aim of this study was to develop a wound dressing using Poly(L-co-D,L lactic acid-co-TMC) (PLDLA-co-TMC) containing aloe vera (AV). This natural plant extract is known for its modulatory effects under healing process. The membrane of PLDLA-co-TMC+aloe vera was prepared at different concentrations of AV (5, 10, 15 and 50%). The FTIR showed no change in the PLDLA-co-TMC spectrum after AV addition, while the swelling test showed changes only in PLDLA-co-TMC+AV at 50%. The wettability measurements showed decrease in the contact angle in all samples after the AV addition in the polymer, while the AV release test showed that PLDLA-co-TMC+50%AV sample has higher AV release rate than the sample with other AV concentrations. The SEM analysis showed that AV was homogeneously distributed at 5% only. Tensile tests demonstrated an increase in the Young's modulus and a reduction in the elongation till rupture of the PLDLA-co-TMC after the addition of AV. Biocompatibility in vitro evaluation with fibroblast cells seeded in the membranes of PLDLA-co-TMC+AV showed that the cells were able to adhere, proliferate and maintain mitochondrial activity in all AV concentrations tested. Due to the known skin medicinal properties attributed to AV and the results here obtained, we suggest that after in vivo trials, the PLDLA-co-TMC+AV should be a promising biomaterial for application as a device for skin curative and healing agent.

PDLLA honeycomb-like scaffolds with a high loading of superhydrophilic graphene/multi-walled carbon nanotubes promote osteoblast in vitro functions and guided in vivo bone regeneration.

Herein, we developed honeycomb-like scaffolds by combining poly (d, l-lactic acid) (PDLLA) with a high amount of graphene/multi-walled carbon nanotube oxides (MWCNTO-GO, 50% w/w). From pristine multi-walled carbon nanotubes (MWCNT) powders, we produced MWCNTO-GO via oxygen plasma etching (OPE), which promoted their exfoliation and oxidation. Initially, we evaluated PDLLA and PDLLA/MWCNTO-GO scaffolds for tensile strength tests, cell adhesion and cell viability (with osteoblast-like MG-63 cells), alkaline phosphatase (ALP, a marker of osteoblast differentiation) activity and mineralized nodule formation. In vivo tests were carried out using PDLLA and PDLLA/MWCNTO-GO scaffolds as fillers for critical defects in the tibia of rats. MWCNTO-GO loading was responsible for decreasing the tensile strength and elongation-at-break of PDLLA scaffolds, although the high mechanical performance observed (~600MPa) assures their application in bone tissue regeneration. In vitro results showed that the scaffolds were not cytotoxic and allowed for osteoblast-like cell interactions and the formation of mineralized matrix nodules. Furthermore, MG-63 cells grown on PDLLA/MWCNTO-GO significantly enhanced osteoblast ALP activity compared to controls (cells alone), while the PDLLA group showed similar ALP activity when compared to controls and PDLLA/MWCNTO-GO. Most impressively, in vivo tests suggested that compared to PDLLA scaffolds, PDLLA/MWCNTO-GO had a superior influence on bone cell activity, promoting greater new bone formation. In summary, the results of this study highlighted that this novel scaffold (MWCNTO-GO, 50% w/w) is a promising alternative for bone tissue regeneration and, thus, should be further studied.