Osteoinductive Bone Morphogenic Protein, Collagen Scaffold, Calcium Phosphate Cement, and Magnesium-Based Fixation Enhance Anterior Cruciate Ligament Tendon Graft to Bone Healing In Animal Models: A Systematic Review.

PURPOSE: To perform a systematic literature review to analyze the results of the in vivo animal models and strategies that use osteoinductive materials to enhance the tendon graft-bone interface for anterior cruciate ligament reconstruction (ACLR). METHODS: Following the Preferred Reporting Items for Systemic Reviews and Meta-Analysis guidelines, the PubMed, Embase, and Web of Science databases were searched. The inclusion criteria were studies of in vivo animal models of ACLR using a material to enhance tendon graft-bone interface healing and reporting at least the histologic results at the interface, along with radiologic and biomechanical data. Studies without control group or with another tendon-bone healing model were excluded. Methodologic quality was assessed with the Animal Research: Reporting In Vivo Experiments 1guidelines. RESULTS: Twenty-seven studies met the inclusion criteria. Rabbit was the main animal model of ACLR, along with sheep and dog models. ACLR procedures varied widely between studies.. The main promising strategies and materials were wrapping the material around the graft, with a collagen scaffold loaded with an osteoinductive molecule (mostly bone morphogenetic proteins). The second strategy consisted of injecting the material at the tendon-bone interface; calcium phosphate cement or a derivative were the most used materials. Finally, using osteoinductive fixation devices was the third strategy; magnesium-based interference screws seemed to show most favorable results. CONCLUSIONS: The studies retained had major methodologic flaws that limit the scope of these conclusions. However, based on histologic, biomechanical, and radiologic analyses, the most promising materials were a collagen scaffold loaded with an osteoinductive molecule and wrapped around the graft, calcium phosphate cement injected in the bone tunnel, and a magnesium-based fixation device. CLINICAL RELEVANCE: In vivo animal models have identified several promising strategies and materials to optimize the tendon-bone interface after ACLR, but standardized and reproducible assessments are needed before these strategies can be adopted clinically.

A Systematic Review of Rat Models With Temporomandibular Osteoarthritis Suitable for the Study of Emerging Prolonged Intra-Articular Drug Delivery Systems.

PURPOSE: Development of minimally invasive therapies for temporomandibular joint osteoarthritis (TMJOA) has focused on drug intra-articular injections to avoid the systemic adverse effects experienced when these substances are administered orally. Therefore, we performed a systematic review to answer the question "Which method of induction of a TMJOA-related pain model in rats leads to prolonged painful symptoms, allowing the best assessment of a sustained drug delivery system?" MATERIALS AND METHODS: Following the PRISMA guidelines, we searched MEDLINE for papers published from 1994 to July 2020 on a TMJ arthritis model using rats. We identified the means of pain induction and of nociception assessment. We assessed protocol bias using an adaptation of the QUADAS-2 tool. Animal selection, the reference standard method of pain assessment, applicability of a statistical assessment, and flow and timing were assessed. RESULTS: Of the 59 full papers we reviewed, 41 performed no pain assessment after the first 7 days following induction of the TMJ-related pain model. We eventually identified 18 long-term TMJOA-related pain models. Pain was induced by injection of toxic substances, most commonly Freund's complete adjuvant (50 µg per 50 µl), formalin at various concentrations, or monosodium iodoacetate (0,5 mg per 50 µl), into the TMJ, or by physical methods. Few studies reported data on pain after 21 days of follow-up. Heterogeneity of induction methods, pain assessment methods, and flow and timing biases precluded a meta-analysis. CONCLUSIONS: Given that pain is 1 of the main symptoms of TMJOA, experimental study protocols should include long-term pain assessment.

Development and Biological Evaluation of Inkjet Printed Drug Coatings on Intravascular Stent.

Inkjet-printing technology was used to apply biodegradable and biocompatible polymeric coatings of poly(d,l-lactide) with the antiproliferative drugs simvastatin (SMV) and paclitaxel (PCX) on coronary metal stents. A piezoelectric dispenser applied coating patterns of very fine droplets (300 pL) and inkjet printing was optimized to develop uniform, accurate and reproducible coatings of high yields on the stent strut. The drug loaded polymeric coatings were assed by scanning electron microscopy (SEM), atomic force microscopy (AFM), and transition thermal microscopy (TTM) where a phase separation was observed for SMV/PLA layers while PCX showed a uniform distribution within the polymer layers. Cytocompatibility studies of PLA coatings showed excellent cell adhesion with no decrease of cell viability and proliferation. In vivo stent implantation studies showed significant intrastent restenosis (ISR) for PCX/PLA and PLA plain coatings similar to marketed Presillion (bare metal) and Cypher (drug eluting) stents. The investigation of several cytokine levels after 7 days of stent deployment showed no inflammatory response and hence no in vivo cytotoxicity related to PLA coatings. Inkjet printing can be employed as a robust coating technology for the development of drug eluting stents compared to the current conventional approaches.

A New Hemodynamic Ex Vivo Model for Medical Devices Assessment.

BACKGROUND: In-stent restenosis (ISR) remains a major public health concern associated with an increased morbidity, mortality, and health-related costs. Drug-eluting stents (DES) have reduced ISR, but generate healing-related issues or hypersensitivity reactions, leading to an increased risk of late acute stent thrombosis. Assessments of new DES are based on animal models or in vitro release systems, which have several limitations. The role of flow and shear stress on endothelial cell and ISR has also been emphasized. The aim of this work was to design and first evaluate an original bioreactor, replicating ex vivo hemodynamic and biological conditions similar to human conditions, to further evaluate new DES. METHODS: This bioreactor was designed to study up to 6 stented arteries connected in bypass, immersed in a culture box, in which circulated a physiological systolo-diastolic resistive flow. Two centrifugal pumps drove the flow. The main pump generated pulsating flows by modulation of rotation velocity, and the second pump worked at constant rotation velocity, ensuring the counter pressure levels and backflows. The flow rate, the velocity profile, the arterial pressure, and the resistance of the flow were adjustable. The bioreactor was placed in an incubator to reproduce a biological environment. RESULTS: A first feasibility experience was performed over a 24-day period. Three rat aortic thoracic arteries were placed into the bioreactor, immersed in cell culture medium changed every 3 days, and with a circulating systolic and diastolic flux during the entire experimentation. There was no infection and no leak. At the end of the experimentation, a morphometric analysis was performed confirming the viability of the arteries. CONCLUSIONS: We designed and patented an original hemodynamic ex vivo model to further study new DES, as well as a wide range of vascular diseases and medical devices. This bioreactor will allow characterization of the velocity field and drug transfers within a stented artery with new functionalized DES, with experimental means not available in vivo. Another major benefit will be the reduction of animal experimentation and the opportunity to test new DES or other vascular therapeutics in human tissues (human infrapopliteal or coronary arteries collected during human donation).

Systematic literature review of in vivo rat femoral defect models using biomaterials to improve the induced membrane technique: a comprehensive analysis.

Purpose: The aim of this study was to conduct a systematic literature review analyzing the results of in vivo rat femoral defect models using biomaterials for improving the induced membrane technique (IMT). Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, the PubMed, Embase, and Web of Science databases were searched. Inclusion criteria were studies reporting results of the IMT in in vivo rat femoral critical-sized defect models using a biomaterial possibly combined with molecules. Methodologic quality was assessed with the Animal Research: Reporting In Vivo Experiments guidelines. Results: Twenty studies met the inclusion criteria. Femoral stabilization with plate and screws was the most frequent. Histologic, biomechanical, and/or radiologic analyses were performed. In two-stage strategies, the PMMA spacer could be associated with bioactive molecules to enhance IM growth factor expression and improve bone formation. Modulating the roughness of spacers could increase IM thickness and accelerate its formation. In one-stage strategies, human tissue-derived membranes combined with bone grafting achieved bone formation comparable to a standard IMT. All calcium phosphate grafts seemed to require a functionalization with growth factors or bone marrow mononuclear cells to improve outcomes compared with non-functionalized grafts. Conclusion: This systematic review described the main parameters of the in vivo rat femoral defect models using biomaterials to improve the induced membrane technique. Although the studies included had several methodological limitations that may limit the scope of these conclusions, one- and two-stage strategies reported promising results with biomaterials to improve the IMT.

Comparison of chemical-induced temporomandibular osteoarthritis rat models (monosodium iodoacetate versus collagenase type II) for the study of prolonged drug delivery systems.

OBJECTIVE: To compare two agents that can induce a rat model of temporomandibular joint osteoarthritis (TMJOA) by chemical induction: monosodium iodoacetate (MIA) and collagenase type 2 (Col-2). We wished to ascertain the best agent for assessing drug-delivery systems (DDSs). METHOD: Male Wistar rats underwent intra-articular injection with MIA or Col-2. They were manipulated for 30 days. The head withdrawal threshold (HWT), immunohistological assessment, and positron emission tomography (PET) were used to evaluate the relevance of our models. RESULTS: For both the MIA and Col-2 groups, pain persisted for 30 days after injection. Change in the HWT showed that Col-2 elicited a strong action initially that decreased progressively. MIA had a constant action upon pain behavior. Histology of TMJ tissue from both groups showed progressive degradation of TMJ components. CONCLUSIONS: MIA and Col-2 induced orofacial pain by their local chemical action on TMJs. However, based on a prolonged and greater sustained effect on the pain threshold, persistent histological changes, and imaging results, MIA appeared to be more suitable for creation of a rat model of TMJOA for the study of DDSs.

Evaluation of a Medical Grade Thermoplastic Polyurethane for the Manufacture of an Implantable Medical Device: The Impact of FDM 3D-Printing and Gamma Sterilization.

Three-dimensional printing (3DP) of thermoplastic polyurethane (TPU) is gaining interest in the medical industry thanks to the combination of tunable properties that TPU exhibits and the possibilities that 3DP processes offer concerning precision, time, and cost of fabrication. We investigated the implementation of a medical grade TPU by fused deposition modelling (FDM) for the manufacturing of an implantable medical device from the raw pellets to the gamma (γ) sterilized 3DP constructs. To the authors' knowledge, there is no such guide/study implicating TPU, FDM 3D-printing and gamma sterilization. Thermal properties analyzed by differential scanning calorimetry (DSC) and molecular weights measured by size exclusion chromatography (SEC) were used as monitoring indicators through the fabrication process. After gamma sterilization, surface chemistry was assessed by water contact angle (WCA) measurement and infrared spectroscopy (ATR-FTIR). Mechanical properties were investigated by tensile testing. Biocompatibility was assessed by means of cytotoxicity (ISO 10993-5) and hemocompatibility assays (ISO 10993-4). Results showed that TPU underwent degradation through the fabrication process as both the number-averaged (Mn) and weight-averaged (Mw) molecular weights decreased (7% Mn loss, 30% Mw loss, p < 0.05). After gamma sterilization, Mw increased by 8% (p < 0.05) indicating that crosslinking may have occurred. However, tensile properties were not impacted by irradiation. Cytotoxicity (ISO 10993-5) and hemocompatibility (ISO 10993-4) assessments after sterilization showed vitality of cells (132% ± 3%, p < 0.05) and no red blood cell lysis. We concluded that gamma sterilization does not highly impact TPU regarding our application. Our study demonstrates the processability of TPU by FDM followed by gamma sterilization and can be used as a guide for the preliminary evaluation of a polymeric raw material in the manufacturing of a blood contacting implantable medical device.

Antiviral functionalization of a polypropylene nonwoven textile structure as a self-decontaminating layer for respiratory masks.

The aim of this work was to develop a filtering biocidal polypropylene (PP) nonwoven textile structure to block and inactivate airborne bacteria and viruses. PP filters were functionalized with a cyclodextrin (CD)-polycarboxylic acid-crosslinked polymer (PP-CD) through a pad/dry/curing process, and were then activated by padding in an alkyl dimethyl benzalkonium chloride (ADBAC) solution. The textile finishing process parameters were optimized with the perspective of mass production, considering the threshold temperature necessary for provoking crosslinking and the limitation of the low thermal stability of PP. The use of an aqueous solution containing hydroxypropyl-ß-cyclodextrin (HPßCD), 1,2,3,4-butanetetracarboxylic acid (BTCA), ammonium hypophosphite (AH), and a surfactant allowed immobilization of the optimal quantity of cyclodextrin polymer under curing for 5 minutes at 125 °C without affecting the nonwoven PP structure. The presence of CD drastically increased the sorption of ADBAC on the textiles. There was leaching of ADBAC at the first rinsing and then satisfactory fastness at the second and third rinsings, revealing adsorption mechanisms by weak physical interactions, ionic interactions, and inclusion of ADBAC inside the CD cavities. SEM revealed no clogging of the nonwoven pores, nor any increase in the air flow resistance, as evaluated by pressure drop measurements. The filtration efficiency of particulate matter PM3.0 and PM0.5 was moderately affected, in contrast to that of PM0.3, which greatly decreased due to the loss of the electrostatic charge of the filter upon the functionalization process. Bactericidal tests resulted in a reduction of 3 log10 against Staphylococcus aureus, and for virucidal tests on human coronavirus HCoV-229E, there was a reduction of 3.4 log10, with both strains undergoing 20 minutes of contact. Finally, the filter we developed is manufacturable by a scalable process, and because of its filtration and biocidal performances, it is a choice material as a self-disinfecting layer in the fabrication of facepiece respirators.

Injectable Chitosan-Based Hydrogels for Trans-Cinnamaldehyde Delivery in the Treatment of Diabetic Foot Ulcer Infections.

Diabetic foot ulcers (DFU) are among the most common complications in diabetic patients and affect 6.8% of people worldwide. Challenges in the management of this disease are decreased blood diffusion, sclerotic tissues, infection, and antibiotic resistance. Hydrogels are now being used as a new treatment option since they can be used for drug delivery and to improve wound healing. This project aims to combine the properties of hydrogels based on chitosan (CHT) and the polymer of ß cyclodextrin (PCD) for local delivery of cinnamaldehyde (CN) in diabetic foot ulcers. This work consisted of the development and characterisation of the hydrogel, the evaluation of the CN release kinetics and cell viability (on a MC3T3 pre-osteoblast cell line), and the evaluation of the antimicrobial and antibiofilm activity (S. aureus and P. aeruginosa). The results demonstrated the successful development of a cytocompatible (ISO 10993-5) injectable hydrogel with antibacterial (99.99% bacterial reduction) and antibiofilm activity. Furthermore, a partial active molecule release and an increase in hydrogel elasticity were observed in the presence of CN. This leads us to hypothesise that a reaction between CHT and CN (a Schiff base) can occur and that CN could act as a physical crosslinker, thus improving the viscoelastic properties of the hydrogel and limiting CN release.

Efficacy of Intra-Articular Injection of Botulinum Toxin Type A (IncobotulinumtoxinA) in Temporomandibular Joint Osteoarthritis: A Three-Arm Controlled Trial in Rats.

Temporomandibular disorders (TMD) are complex pathologies responsible for chronic orofacial pain. Intramuscular injection of botulinum toxin A (BoNT/A) has shown effectiveness in knee and shoulder osteoarthritis, as well as in some TMDs such as masticatory myofascial pain, but its use remains controversial. This study aimed to evaluate the effect of intra-articular BoNT/A injection in an animal model of temporomandibular joint osteoarthritis. A rat model of temporomandibular osteoarthritis was used to compare the effects of intra-articular injection of BoNT/A, placebo (saline), and hyaluronic acid (HA). Efficacy was compared by pain assessment (head withdrawal test), histological analysis, and imaging performed in each group at different time points until day 30. Compared with the rats receiving placebo, those receiving intra-articular BoNT/A and HA had a significant decrease in pain at day 14. The analgesic effect of BoNT/A was evident as early as day 7, and lasted until day 21. Histological and radiographic analyses showed decrease in joint inflammation in the BoNT/A and HA groups. The osteoarthritis histological score at day 30 was significantly lower in the BoNT/A group than in the other two groups (p = 0.016). Intra-articular injection of BoNT/A appeared to reduce pain and inflammation in experimentally induced temporomandibular osteoarthritis in rats.

In Vitro and In Vivo Evaluation of a Bio-Inspired Adhesive for Bone Fixation.

Compared to metallic hardware, an effective bone adhesive can revolutionize the treatment of clinically challenging situations such as comminuted, articular, and pediatric fractures. The present study aims to develop such a bio-inspired bone adhesive, based upon a modified mineral-organic adhesive with tetracalcium phosphate (TTCP) and phosphoserine (OPS) by incorporating nanoparticles of polydopamine (nPDA). The optimal formulation, which was screened using in vitro instrumental tensile adhesion tests, was found to be 50%molTTCP/50%molOPS-2%wtnPDA with a liquid-to-powder ratio of 0.21 mL/g. This adhesive has a substantially stronger adhesive strength (1.0-1.6 MPa) to bovine cortical bone than the adhesive without nPDA (0.5-0.6 MPa). To simulate a clinical scenario of autograft fixation under low mechanical load, we presented the first in vivo model: a rat fibula glued to the tibia, on which the TTCP/OPS-nPDA adhesive (n = 7) was shown to be effective in stabilizing the graft without displacement (a clinical success rate of 86% and 71% at 5 and 12 weeks, respectively) compared to a sham control (0%). Significant coverage of newly formed bone was particularly observed on the surface of the adhesive, thanks to the osteoinductive property of nPDA. To conclude, the TTCP/OPS-nPDA adhesive fulfilled many clinical requirements for the bone fixation, and potentially could be functionalized via nPDA to offer more biological activities, e.g., anti-infection after antibiotic loading.

Limitation of the migration of plasticizers from medical devices through treatment with low-pressure cold plasma, polydopamine coating, and annealing.

Poly(vinyl chloride) (PVC) is widely used in the manufacture of medical devices. The plasticizers added to PVC are potentially toxic for humans, likely to migrate, and thus unintentionally administered to patients. The objective of the present study was to reduce the migration of plasticizer (1,2-cyclohexanedicarboxylic acid, diisononylester (DINCH) or trioctyltrimellitate (TOTM)) from PVC by implementing a three-step surface treatment process: (i) pretreatment with low-pressure argon cold plasma, (ii) polydopamine coating, and (iii) post-treatment with cold plasma exposure or thermal treatment at 140 °C. Samples were then characterized in terms of the water contact angle (WCA) and the aspect in scanning electron microscopy. Plasticizer migration (n = 5) was measured using an HPLC technique with ultraviolet detection and found to depend on the treatment and the plasticizer. Plasticized PVC was hydrophobic, with a measured mean ± standard deviation WCA of 96.7 ± 3.6° for PVC-DINCH and 110.2 ± 5.8° for PVC-TOTM. Plasma post-treatment and thermal post-treatment were respectively associated with a mean decrease in migration of 38.3 ± 1.9% for DINCH and 61.5 ± 4.4% for TOTM. Our results are promising with regard to limiting the migration of plasticizers into the patient's blood and thus enabling the development of safer medical devices.

Core-Sheath Electrospun Nanofibers Based on Chitosan and Cyclodextrin Polymer for the Prolonged Release of Triclosan.

This work focuses on the manufacture of core-sheath nanofibers (NFs) based on chitosan (CHT) as sheath and cyclodextrin polymer (PCD) as core and loaded with triclosan (TCL). In parallel, monolithic NFs consisting of blended CHT-PCD and TCL were prepared. Nanofibers were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Fourier Transform Infrared spectroscopy (FTIR). SEM displayed the morphology of NFs and the structure of the nanowebs, while TEM evidenced the core-sheath structure of NFs prepared by coaxial electrospinning. The core diameters and sheath thicknesses were found dependent on respective flow rates of both precursor solutions. Nanofibers stability and TCL release in aqueous medium were studied and correlated with the antibacterial activity against Staphylococcus aureus and Escherichia coli. Results showed that the release profiles of TCL and therefore the antibacterial activity were directly related to the type of nanofibers. In the case of monolithic nanofibers, the NFs matrix was composed of polyelectrolyte complex (PEC formed between CHT and PCD) and resulted in a prolonged release of TCL and a sustained antibacterial effect. In the case of core-sheath NFs, the PEC was formed only at the core-sheath interface, leading to less stable NFs and therefore to a faster release of TCL, and to a less extended antibacterial activity compared to monolithic ones.

Systematic review of studies on drug-delivery systems for management of temporomandibular-joint osteoarthritis.

INTRODUCTION: Temporomandibular-joint osteoarthritis (TMJOA) management is a major challenge. Minimally invasive therapies (based mainly on injections) have been developed to increase local efficacy and limit adverse systemic effects. However, the requirement for repeat injections due to a short duration of action and expensive healthcare costs have pushed researchers to develop, via tissue engineering, drug-delivery systems (DDSs). In this literature systematic review, we aim to provide an overview of studies that tested DDSs on a TMJOA model. MATERIAL AND METHODS: We searched on PubMed for articles published from November 1965 to March 2021 on DDSs using a TMJOA model. We highlighted the different DDSs and the active molecule employed. Route of drug administration, model type, test duration, and efficacy duration were assessed. To evaluate the quality of each study, a protocol bias was tested using QUADAS-2™. RESULTS: Of the 10 studies that were full text-screened, four used a poly(lactic-co-glycolic acid)-based delivery system. The other DDSs employed chitosan-based hydrogels, microneedles patches, nanostructured lipid carriers, or poloxamer micelles. Hyaluronic acid, nonsteroidal anti-inflammatory drugs, and analgesics were used as active molecules in five studies. The main way to administer DDSs was intra-articular injection and the most used model was the rat. DISCUSSION: Various DDSs and active molecules have been studied on a TMJOA model that could aid TMJOA management. Further works using longer test durations are necessary to validate these advances.

Polydopamine treatment of chitosan nanofibers for the conception of osteoinductive scaffolds for bone reconstruction.

We report the influence of treatment time of electrospun chitosan nanofibers (CHT NFs) in dopamine hydrochloride bath (2 mg.mL-1 in 10 mM Tris buffer, pH 8.5) on the extent of the polydopamine (pDA) coating on NFs surface. The reaction was characterized by FTIR and SEM analysis and the cytocompatibility of the scaffolds toward MT3C3-E1 cells was assessed. Biomimetic deposition of hydroxyapatite (HA) in 1.5xSBF batch was investigated by SEM-EDS and XRD. Samples treated in dopamine bath during 2 h promoted the structural stability of NFs in PBS, provided optimal cytocompatibility and induced the in vitro biomineralization from 6 days in 1.5xSBF. The XRD and SEM-EDS investigations confirmed formation of spherical-shaped particles composed of apatitic phase. Finally, this study shows that these NFs-pDA scaffolds prepared in the optimal experimental conditions defined here are promising candidates for application as osteoinductive scaffolds for bone regeneration applied to orthopedic and dental applications.

Electrospun Filtering Membrane Designed as Component of Self-Decontaminating Protective Masks.

The 2019 coronavirus outbreak and worsening air pollution have triggered the search for manufacturing effective protective masks preventing both particulate matter and biohazard absorption through the respiratory tract. Therefore, the design of advanced filtering textiles combining efficient physical barrier properties with antimicrobial properties is more newsworthy than ever. The objective of this work was to produce a filtering electrospun membrane incorporating a biocidal agent that would offer both optimal filtration efficiency and fast deactivation of entrapped viruses and bacteria. After the eco-friendly electrospinning process, polyvinyl alcohol (PVA) nanofibers were stabilized by crosslinking with 1,2,3,4-butanetetracarboxylic acid (BTCA). To compensate their low mechanical properties, nanofiber membranes with variable grammages were directly electrospun on a meltblown polypropylene (PP) support of 30 g/m2. The results demonstrated that nanofibers supported on PP with a grammage of around only 2 g/m2 presented the best compromise between filtration efficiencies of PM0.3, PM0.5, and PM3.0 and the pressure drop. The filtering electrospun membranes loaded with benzalkonium chloride (ADBAC) as a biocidal agent were successfully tested against E. coli and S. aureus and against human coronavirus strain HCoV-229E. This new biocidal filter based on electrospun nanofibers supported on PP nonwoven fabric could be a promising solution for personal and collective protection in a pandemic context.

Preclinical Study of Radiation on Fat Flap Regeneration under Tissue-engineering Chamber: Potential Consequences for Breast Reconstruction.

Use of a tissue-engineering chamber (TEC) for growth of fat flap is a promising approach for breast reconstruction. Here, we evaluated in a preclinical model the effects of radiation on adipose tissue growth either before or after 3D-printed bioresorbable TEC implantation. Methods: Twenty-eight female Wistar rats were distributed into three groups: TEC implantation as nonirradiated controls (G1), TEC insertion followed by irradiation 3 weeks later (G2), and irradiation 6 weeks before TEC insertion (G3). G2 and G3 received 33.3 Gy in nine sessions of 3.7 Gy. Growth of the fat flap was monitored via magnetic resonance imaging. At 6 months after implantation, fat flaps and TECs were harvested for analysis. Results: Irradiation did not alter the physicochemical features of poly(lactic-co-glycolic acid)-based TECs. Compared with G1, fat flap growth was significantly reduced by 1.6 times in irradiated G2 and G3 conditions. In G2 and G3, fat flaps consisted of mature viable adipocytes sustained by CD31+ vascular cells. However, 37% (3 of 8) of the G2 irradiated adipose tissues presented a disorganized architecture invaded by connective tissues with inflammatory CD68 + cells, and the presence of fibrosis was observed. Conclusions: Overall, this preclinical study does not reveal any major obstacle to the use of TEC in a radiotherapy context. Although irradiation reduces the growth of fat flap under the TEC by reducing adipogenesis and inducing inconsistent fibrosis, it does not impact flap survival and vascularization. These elements must be taken into account if radiotherapy is proposed before or after TEC-based breast reconstruction.

Effects of Two Melt Extrusion Based Additive Manufacturing Technologies and Common Sterilization Methods on the Properties of a Medical Grade PLGA Copolymer.

Although bioabsorbable polymers have garnered increasing attention because of their potential in tissue engineering applications, to our knowledge there are only a few bioabsorbable 3D printed medical devices on the market thus far. In this study, we assessed the processability of medical grade Poly(lactic-co-glycolic) Acid (PLGA)85:15 via two additive manufacturing technologies: Fused Filament Fabrication (FFF) and Direct Pellet Printing (DPP) to highlight the least destructive technology towards PLGA. To quantify PLGA degradation, its molecular weight (gel permeation chromatography (GPC)) as well as its thermal properties (differential scanning calorimetry (DSC)) were evaluated at each processing step, including sterilization with conventional methods (ethylene oxide, gamma, and beta irradiation). Results show that 3D printing of PLGA on a DPP printer significantly decreased the number-average molecular weight (Mn) to the greatest extent (26% Mn loss, p < 0.0001) as it applies a longer residence time and higher shear stress compared to classic FFF (19% Mn loss, p < 0.0001). Among all sterilization methods tested, ethylene oxide seems to be the most appropriate, as it leads to no significant changes in PLGA properties. After sterilization, all samples were considered to be non-toxic, as cell viability was above 70% compared to the control, indicating that this manufacturing route could be used for the development of bioabsorbable medical devices. Based on our observations, we recommend using FFF printing and ethylene oxide sterilization to produce PLGA medical devices.

How Adding Chlorhexidine or Metallic Nanoparticles Affects the Antimicrobial Performance of Calcium Hydroxide Paste as an Intracanal Medication: An In Vitro Study.

The aim of our study was to explore the potential value of metallic (Ag, Cu, and Zn) salts, polymer/metallic nanoparticles, and chlorhexidine (CHX) for improving the antimicrobial activity of calcium hydroxide (CH) against E. faecalis and C. albicans, associated with persistent endodontic infections. A first screening was performed by determining minimum inhibitory/bactericidal concentrations (MIC/MBC). Antimicrobial activity of the CH paste mixed with metallic salts, chitosan or cyclodextrin polymer metallic nanoparticles was compared to the antimicrobial activity of CH paste alone and CH + CHX using a time-kill kinetics assay. The effect of the antimicrobials on the rheological and the key mechanical properties were also examined. Copper and zinc were discarded because of their MIC/MBC values and silver because of its kill time curve profile. Except for a slower setting time after 24 h and a higher weight loss after 1 week of incubation, the mechanical behavior of the CH paste was unaffected by the addition of CHX. Polymeric/metallic nanoparticles failed to potentiate the antimicrobial effect of CH. By contrast, CHX increased this effect and thus could help eradicate E. faecalis associated with persistent root canal infections without altering the desired key physical properties of the CH paste.

In Vitro Microbiological and Drug Release of Silver/Ibuprofen Loaded Wound Dressing Designed for the Treatment of Chronically Infected Painful Wounds.

This study consisted of developing a dressing loaded with silver (Ag) and ibuprofen (IBU) that provides a dual therapy, antibacterial and antalgic, intended for infected painful wounds. Therefore, non-woven polyethyleneterephtalate (PET) textiles nonwovens were pre-treated by cyclodextrin crosslinked with citric acid by a pad/dry/cure process. Then, textiles were impregnated in silver solution followed by a thermal treatment and were then coated by Layer-by-Layer (L-b-L) deposition of a polyelectrolyte multilayer (PEM) system consisting of anionic water-soluble poly(betacyclodextrin citrate) (PCD) and cationic chitosan. Finally, ibuprofen lysinate (IBU-L) was loaded on the PEM coating. We demonstrated the complexation of IBU with native ßCD and PCD by phase solubility diagram and 1H NMR. PEM system allowed complete IBU-L release in 6 h in PBS pH 7.4 batch (USP IV). On the other hand, microbiological tests demonstrated that loaded silver induced bacterial reduction of 4 Log10 against S. aureus and E. coli and tests revealed that ibuprofen lysinate loading did not interfere with the antibacterial properties of the dressing.