Search results for: bioresorbable

Authors: Chee Wee Gan, Anthony Herr Cheun Ng, Yee Shan Wong, Subbu Venkatraman, Lynne Hsueh Yee Lim

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Otitis media with effusion (OME) is the leading cause of hearing loss in children worldwide. Surgery to insert grommet tube into the eardrum is usually indicated for OME unresponsive to antimicrobial therapy. It is the most common surgery for children. However, current commercially available grommet tubes are non-bioresorbable, not drug-treated, with unpredictable duration of retention on the eardrum to ventilate middle ear. Their functionality is impaired when clogged or chronically infected, requiring additional surgery to remove/reinsert grommet tubes. We envisaged that a novel fully bioresorbable grommet tube with sustained antibiotic release technology could address these drawbacks. In this study, drug-loaded bioresorbable poly(L-lactide-co-ε-caprolactone)(PLC) copolymer grommet tubes were fabricated by microinjection moulding technique. In vitro drug release and degradation model of PLC tubes were studied. Antibacterial property was evaluated by incubating PLC tubes with P. aeruginosa broth. Surface morphology was analyzed using scanning electron microscopy. A preliminary animal study was conducted using guinea pigs as an in vivo model to evaluate PLC tubes with and without drug, with commercial Mini Shah grommet tube as comparison. Our in vitro data showed sustained drug release over 3 months. All PLC tubes revealed exponential degradation profiles over time. Modeling predicted loss of tube functionality in water to be approximately 14 weeks and 17 weeks for PLC with and without drug, respectively. Generally, PLC tubes had less bacteria adherence, which were attributed to the much smoother tube surfaces compared to Mini Shah. Antibiotic from PLC tube further made bacteria adherence on surface negligible. They showed neither inflammation nor otorrhea after 18 weeks post-insertion in the eardrums of guinea pigs, but had demonstrated severe degree of bioresorption. Histology confirmed the new PLC tubes were biocompatible. Analyses on the PLC tubes in the eardrums showed bioresorption profiles close to our in vitro degradation models. The bioresorbable antibiotic-loaded grommet tubes showed good predictability in functionality. The smooth surface and sustained release technology reduced the risk of tube infection. Tube functional duration of 18 weeks allowed sufficient ventilation period to treat OME. Our ongoing studies include modifying the surface properties with protein coating, optimizing the drug dosage in the tubes to enhance their performances, evaluating their functional outcome on hearing after full resoption of grommet tube and healing of eardrums, and developing animal model with OME to further validate our in vitro models.

Keywords: bioresorbable polymer, drug release, grommet tube, guinea pigs, otitis media with effusion

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Authors: Carolina Pereira Lobato Costa, Cristina Pascual-González, Monica Echeverry, Javier LLorca, Carlos Gonzáléz, Juan Pedro Fernández-Bláquez

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Although the potential of PLA self-reinforced composites for bone applications, not much literature addresses optimal manufacturing conditions. In this regard, this paper describes the woven self-reinforced PLA composites manufacturing processes: the commingling of yarns, weaving, and hot pressing and characterizes the manufactured laminates. Different structures and properties can be achieved by varying the hot compaction process parameters (pressure, holding time, and temperature). The specimens manufactured were characterized in terms of thermal properties (DSC), microstructure (C-scan optical microscope and SEM), strength (tensile test), and biocompatibility (MTT assays). Considering the final device, 155 ℃ for 10 min at 2 MPa act as the more appropriate hot pressing parameters. The laminate produced with these conditions has few voids/porosity, a tensile strength of 30.39 ± 1.21 MPa, and a modulus of 4.09 ± 0.24 GPa. Subsequently to the tensile testing was possible to observe fiber pullout from the fracture surfaces, confirming that this material behaves as a composite. From the results, no single laminate can fulfill all the requirements, being necessary to compromise in function of the priority property. Further investigation is required to improve materials' mechanical performance. Subsequently, process parameters and materials configuration can be adjusted depending on the place and type of implant to suit its function.

Keywords: woven fabric, self-reinforced polymer composite, poly(lactic acid), biodegradable

Procedia PDF Downloads 194

Authors: Stefan Gruden, Charlott Brunmark, Bo Holmqvist, Erwin D. Brenndorfer, Martin Johansson, Jian Liu, Ying Zhao, Niklas Axen, Moustapha Hassan

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Aim: The study was designed to evaluate the ability of the calcium sulfate-based NanoZolid® drug delivery technology to locally release the epidermal growth factor (EGF) protein while maintaining its biological activity. Methods: NanoZolid-formulated EGF protein labelled with a near-infrared dye (EGF-NIR) depots or EGF-NIR dissolved in PBS were injected subcutaneously into mice bearing EGF receptor (EGFR) positive human A549 lung cancer tumors inoculated subcutaneously. The release and biodistribution of the EGF-NIR were investigated in vivo longitudinally up to 96 hours post-administration, utilizing whole-body fluorescence imaging. In order to confirm the in vivo findings, histological analysis of tumor cryosections was performed to investigate EGF-NIR fluorescent signal and EGFR expression level by immunofluorescence labelling. Results: The in vivo fluorescence imaging showed a controlled release profile of the EGF-NIR loaded in the NanoZolid depots compared to free EGF-NIR. Histological analysis of the tumors further demonstrated a prevailing distribution of EGF-NIR in regions with high levels of EGFR expression. Conclusion: Calcium sulfate based depots can be used to formulate EGF while maintaining its biological activity, e.g., receptor binding capability. This may have good clinical potential for local delivery of biomolecules to enhance treatment efficacy and minimize systemic adverse effects.

Keywords: bioresorbable, calcium sulfate, controlled release, NanoZolid

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Authors: Amir Reza Heydari, Yaser Jenab

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Coronary artery disease, a common cardiovascular disease, is attributed to the accumulation of cholesterol-based plaques in the coronary arteries, leading to atherosclerosis. This disease is associated with risk factors such as smoking, hypertension, diabetes, and elevated cholesterol levels, contributing to severe clinical consequences, including acute coronary syndromes and myocardial infarction. Treatment approaches such as from lifestyle interventions to surgical procedures like percutaneous coronary intervention and coronary artery bypass surgery. These interventions often employ stents, including bare-metal stents (BMS), drug-eluting stents (DES), and bioresorbable vascular scaffolds (BVS), each with its advantages and limitations. Computational tools have emerged as critical in optimizing stent designs and assessing their performance. The aim of this study is to provide an overview of the computational methods of studies based on the finite element (FE) method in the field of coronary stenting and discuss the potential for development and clinical application of stent devices. Additionally, the importance of assessing the ability of computational models is emphasized to represent real-world phenomena, supported by recent guidelines from the American Society of Mechanical Engineers (ASME). Validation processes proposed include comparing model performance with in vivo, ex-vivo, or in vitro data, alongside uncertainty quantification and sensitivity analysis. These methods can enhance the credibility and reliability of in silico simulations, ultimately aiding in the assessment of coronary stent designs in various clinical contexts.

Keywords: atherosclerosis, materials, restenosis, review, validation

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Authors: C. Busuioc, I. Stancu, A. Nicoara, A. Zamfirescu, A. Evanghelidis

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The field of tissue engineering has expanded its potential due to the use of composite biomaterials belonging to increasingly complex systems, leading to bone substitutes with properties that are continuously improving to meet the patient's specific needs. Furthermore, the development of biomaterials based on ceramic and polymeric phases is an unlimited resource for future scientific research, with the final aim of restoring the original tissue functionality. Thus, in the first stage, composite scaffolds based on polycaprolactone (PCL) or polylactic acid (PLA) and inorganic powders were prepared by employing the electrospinning technique. The targeted powders were: commercial and laboratory synthesized hydroxyapatite (HAp), as well as barium titanate (BT). By controlling the concentration of the powder within the precursor solution, together with the processing parameters, different types of three-dimensional architectures were achieved. In the second stage, both the mineral powders and hybrid composites were investigated in terms of composition, crystalline structure, and microstructure so that to demonstrate their suitability for tissue engineering applications. Regarding the scaffolds, these were proven to be homogeneous on large areas and loaded with mineral particles in different proportions. The biological assays demonstrated that the addition of inorganic powders leads to modified responses in the presence of simulated body fluid (SBF) or cell cultures. Through SBF immersion, the biodegradability coupled with bioactivity were highlighted, with fiber fragmentation and surface degradation, as well as apatite layer formation within the testing period. Moreover, the final composites represent supports accepted by the cells, favoring implant integration. Concluding, the purposed fibrous materials based on bioresorbable polymers and mineral powders, produced by the electrospinning technique, represent candidates with considerable potential in the field of tissue engineering. Future improvements can be attained by optimizing the synthesis process or by simultaneous incorporation of multiple inorganic phases with well-defined biological action in order to fabricate multifunctional composites.

Keywords: barium titanate, electrospinning, fibre networks, hydroxyapatite, smart scaffolds

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Authors: Sarah Pasala, Elizabeth Zacharias

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Vital sign monitoring is crucial for both everyday health and medical diagnosis. A significant factor in assessing a human's health is their vital signs, which include heart rate, breathing rate, blood pressure, and electrocardiogram (ECG) readings. Vital sign monitoring has been the focus of many system and method innovations recently. Piezoelectrics are materials that convert mechanical energy into electrical energy and can be used for vital sign monitoring. Piezoelectric energy harvesters that are stretchable and flexible can detect very low frequencies like airflow, heartbeat, etc. Current advancements in piezoelectric materials and flexible sensors have made it possible to create wearable and implantable medical devices that can continuously monitor physiological signals in humans. But because of their non-biocompatible nature, they also produce a large amount of e-waste and require another surgery to remove the implant. This paper presents a biocompatible and flexible piezoelectric composite material for wearable and implantable devices that offers a high-performance platform for seamless and continuous monitoring of human physiological signals and tactile stimuli. It also addresses the issue of e-waste and secondary surgery. A Lead-free piezoelectric, SrBi4Ti4O15, is found to be suitable for this application because the properties can be tailored by suitable substitutions and also by varying the synthesis temperature protocols. In the present work, SrBi4Ti4O15 modified by rare-earth has been synthesized and studied. Coupling factors are calculated from resonant (fr) and anti-resonant frequencies (fa). It is observed that Samarium substitution in SBT has increased the Curie temperature, dielectric and piezoelectric properties. From impedance spectroscopy studies, relaxation, and non-Debye type behaviour are observed. The composite of bioresorbable poly(l-lactide) and Lead-free rare earth modified Bismuth Layered Ferroelectrics leads to a flexible piezoelectric device for non-invasive measurement of vital signs, such as heart rate, breathing rate, blood pressure, and electrocardiogram (ECG) readings and also artery pulse signals in near-surface arteries. These composites are suitable to detect slight movement of the muscles and joints. This Lead-free rare earth modified Bismuth Layered Ferroelectrics – polymer composite is synthesized using a ball mill and the solid-state double sintering method. XRD studies indicated the two phases in the composite. SEM studies revealed the grain size to be uniform and in the range of 100 nm. The electromechanical coupling factor is improved. The elastic constants are calculated and the mechanical flexibility is found to be improved as compared to the single-phase rare earth modified Bismuth Latered piezoelectric. The results indicate that this composite is suitable for the non-invasive detection of multiple vital signs of humans.

Keywords: composites, flexible, non-invasive, piezoelectric

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Authors: Irene Carmagnola, Valeria Chiono, Sandra Pacharra, Jochen Salber, Sean McMahon, Chris Lovell, Pooja Basnett, Barbara Lukasiewicz, Ipsita Roy, Xiang Zhang, Gianluca Ciardelli

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Thrombosis and restenosis after stenting procedure can be prevented by promoting fast stent wall endothelialisation. It is well known that surface functionalisation with antifouling molecules combining with extracellular matrix proteins is a promising strategy to design biomimetic surfaces able to promote fast endothelialization. In particular, REDV has gained much attention for the ability to enhance rapid endothelialization due to its specific affinity with endothelial cells (ECs). In this work, a two-step plasma treatment was performed to polymerize a thin layer of acrylic acid, used to subsequently graft PEGylated-REDV and polyethylene glycol (PEG) at different molar ratio with the aim to selectively promote endothelial cell adhesion avoiding platelet activation. PEGylate-REDV was provided by Biomatik and it is formed by 6 PEG monomer repetitions (Chempep Inc.), with an NH2 terminal group. PEG polymers were purchased from Chempep Inc. with two different chain lengths: m-PEG6-NH2 (295.4 Da) with 6 monomer repetitions and m-PEG12-NH2 (559.7 Da) with 12 monomer repetitions. Plasma activation was obtained by operating at 50W power, 5 min of treatment and at an Ar flow rate of 20 sccm. Pure acrylic acid (99%, AAc) vapors were diluted in Ar (flow = 20 sccm) and polymerized by a pulsed plasma discharge applying a discharge RF power of 200 W, a duty cycle of 10% (on time = 10 ms, off time = 90 ms) for 10 min. After plasma treatment, samples were dipped into an 1-(3-dimethylaminopropyl)-3- ethylcarbodiimide (EDC)/N-hydroxysuccinimide (NHS) solution (ratio 4:1, pH 5.5) for 1 h at 4°C and subsequently dipped in PEGylate-REDV and PEGylate-REDV:PEG solutions at different molar ratio (100 μg/mL in PBS) for 20 h at room temperature. Surface modification was characterized through physico-chemical analyses and in vitro cell tests. PEGylated-REDV peptide and PEG were successfully bound to the carboxylic groups that are formed on the polymer surface after plasma reaction. FTIR-ATR spectroscopy, X -ray Photoelectron Spectroscopy (XPS) and contact angle measurement gave a clear indication of the presence of the grafted molecules. The use of PEG as a spacer allowed for an increase in wettability of the surface, and the effect was more evident by increasing the amount of PEG. Endothelial cells adhered and spread well on the surfaces functionalized with the REDV sequence. In conclusion, a selective coating able to promote a new endothelial cell layer on polymeric stent surface was developed. In particular, a thin AAc film was polymerised on the polymeric surface in order to expose –COOH groups, and PEGylate-REDV and PEG were successful grafted on the polymeric substrates. The REDV peptide demonstrated to encourage cell adhesion with a consequent, expected improvement of the hemocompatibility of these polymeric surfaces in vivo. Acknowledgements— This work was funded by the European Commission 7th Framework Programme under grant agreement number 604251- ReBioStent (Reinforced Bioresorbable Biomaterials for Therapeutic Drug Eluting Stents). The authors thank all the ReBioStent partners for their support in this work.

Keywords: endothelialisation, plasma treatment, stent, surface functionalisation

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Authors: Divya SY. Ang, Mark B. Tan, Nicholas EM. Yeo, Siti RB. Sudirman, Khong Yik Chew

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Introduction: The importance of the amalgamation of technological and engineering advances with surgical principles of reconstruction cannot be overemphasized. With earlier detection of cancer, consequences of high-speed living and neglect, like traumatic injuries and infection, resulting in increasingly younger patients with bone defects. This may result in malformations and suboptimal function that is more noticeable and palpable in the younger, active demographic. Our team proposes a technique that encapsulates a mesh of multidisciplinary effort, tissue engineering and reconstructive principles. Methods/Materials: Our patient was a young competitive footballer in his early 30s who was diagnosed with submandibular adenoid cystic carcinoma with bony involvement. He was thus counselled for a right hemi mandibulectomy, the floor of mouth resection, right selective neck dissection, tracheostomy, and free fibular flap reconstruction of his mandible and required post-operative radiotherapy. Being young and in his prime sportsman years, he was unable to accept the morbidities associated with using his fibula to reconstruct his mandible despite it being the gold standard reconstructive option. The fibula is an ideal vascularized bone flap because it’s reliable and easily shaped with relatively minimal impact on functional outcomes. The fibula contributes to 30% of weightbearing and is the attachment for the lateral compartment muscles; it is stronger in footballers concerning lateral bending. When harvesting the fibula, the distal 6-8cm and up to 10% of the total length is preserved to maintain the ankle’s stability, thus, minimizing the impact on daily activities. There are studies that have noted gait variability post-operatively. Therefore, returning to a premorbid competitive level may be doubtful. To improve his functional outcomes, the decision was made to try and restore the fibula's form and function. Using the concept of Fused Deposition Modelling (FDM), our team comprising of Plastics, Otolaryngology, Orthopedics and Radiology, worked with Osteopore to design a 3D bioresorbable implant to regenerate the fibula defect (14.5cm). Bone marrow was harvested via reaming the contralateral hip prior to the wide resection. 30mls of his blood was obtained for extracting platelet rich plasma. These were packed into the Osteopore 3D-printed bone scaffold. This was then secured into the fibula defect with titanium plates and screws. The flexor hallucis longus and soleus were anchored along the construct and intraosseous membrane, done in a single setting. Results: He was reviewed closely as an outpatient over 10 months post operatively. He reported no discernable loss or difference in ankle function. He is satisfied and back in training and our team has video and photographs that substantiate his progress. Conclusion: FDM allows regeneration of long bone defects. However, we aimed to also restore his eversion and inversion that is imperative for footballers and hence reattached his previously dissected muscles along the length of the Osteopore implant. We believe that the reattachment of the muscle stabilizes not only the construct but allows optimum muscle tensioning when moving his ankle. This is a simple but effective technique in restoring complete function and form in a young patient whose minute muscle control is imperative to life.

Keywords: fused deposition modelling, functional reconstruction, lower limb bony defects, regenerative surgery, 3D printing, tissue engineering

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