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Islet transplantation for type 1 diabetes treatment has been limited by the need for lifelong immunosuppression regimens. This challenge has prompted the development of macroencapsulation devices (MEDs) to immunoprotect the transplanted islets. While promising, conventional MEDs are faced with insufficient transport of oxygen, glucose, and insulin because of the reliance on passive diffusion. Hence, these devices are constrained to two-dimensional, wafer-like geometries with limited loading capacity to maintain cells within a distance of passive diffusion. We hypothesized that convective nutrient transport could extend the loading capacity while also promoting cell viability, rapid glucose equilibration, and the physiological levels of insulin secretion. Here, we showed that convective transport improves nutrient delivery throughout the device and affords a three-dimensional capsule geometry that encapsulates 9.7-fold-more cells than conventional MEDs. Transplantation of a convection-enhanced MED (ceMED) containing insulin-secreting ß cells into immunocompetent, hyperglycemic rats demonstrated a rapid, vascular-independent, and glucose-stimulated insulin response, resulting in early amelioration of hyperglycemia, improved glucose tolerance, and reduced fibrosis. Finally, to address potential translational barriers, we outlined future steps necessary to optimize the ceMED design for long-term efficacy and clinical utility.
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Encapsulamento de Células/métodos , Sistemas de Liberação de Medicamentos/métodos , Células Secretoras de Insulina/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Convecção , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Sistemas de Liberação de Medicamentos/instrumentação , Insulina/metabolismo , Secreção de Insulina/efeitos dos fármacos , Secreção de Insulina/fisiologia , Células Secretoras de Insulina/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Transplante das Ilhotas Pancreáticas/métodos , Masculino , RatosRESUMO
Microneedles have recently been adopted for use as a painless and safe method of transdermal therapeutic delivery through physically permeating the stratum corneum. While microneedles create pathways to introduce drugs, they can also act as conduits for biosignal sensing. Here, we explore the development of microneedles as both biosensing and drug delivery platforms. Microneedle sensors are being developed for continuous monitoring of biopotentials and bioanalytes through the use of conductive and electrochemically reactive biomaterials. The range of therapeutics being delivered through microneedle devices has diversified, while novel bioabsorbable microneedles are undergoing first-in-human clinical studies. We foresee that future microneedle platform development will focus on the incorporation of biofunctional materials, designed to deliver therapeutics in a stimulus responsive fashion. Biofunctional microneedle patches will require improved methods of attaching to and conforming to epithelial tissues in dynamic environments for longer periods of time and thus present an assortment of new design challenges. Through the evolution of biomaterial development and microneedle design, biofunctional microneedles are proposed as a next generation of stimulus responsive drug delivery systems.
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Técnicas Biossensoriais/instrumentação , Sistemas de Liberação de Medicamentos/instrumentação , Agulhas , Adesivo Transdérmico , Administração Cutânea , Animais , Técnicas Biossensoriais/métodos , Sistemas de Liberação de Medicamentos/métodos , Desenho de Equipamento , Humanos , Pele/metabolismoRESUMO
Understanding of the mechanical properties of skin is crucial in evaluating the performance of skin-interfacing medical devices. Artificial skin models (ASMs) have rapidly gained attention as they are able to overcome the challenges in ethically sourcing consistent and representative ex vivo animal or human tissue models. Although some ASMs have become commercialised, a thorough understanding of the mechanical properties of the skin models is crucial to ensure that they are suitable for the purpose of the study. In the present study, skin and fat layers of ASMs (Simulab®, LifeLike®, SynDaver® and Parafilm®) were mechanically characterised through hardness, needle insertion, tensile and compression testing. Different boundary constraint conditions (minimally and highly constrained) were investigated for needle insertion testing, while anisotropic properties of the skin models were investigated through different specimen orientations during tensile testing. Analysis of variance (ANOVA) tests were performed to compare the mechanical properties between the skin models. Properties of the skin models were compared against literature to determine the suitability of the skin models based on the material property of interest. All skin models offer relatively consistent mechanical performance, providing a solid basis for benchtop evaluation of skin-interfacing medical device performance. Through prioritising models with mechanical properties that are consistent with human skin data, and with limited variance, researchers can use the data presented here as a toolbox to select the most appropriate ASM for their particular application.
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Current procedures for transdermal drug delivery (TDD) have associated limitations including poor administration of nucleic acid, small or large drug molecules, pain and stress for needle phobic people. A painless micro-sized device capable of delivering drugs easily and efficiently, eliminating the disadvantages of traditional systems, has yet to be developed. While polymeric-based microneedle (MN) arrays have been used successfully and clinically as TDD systems, these devices lack mechanical integrity, piercing capacity and the ability to achieve tailored drug release into the systemic circulation. Recent advances in micro/nano fabrication techniques using Additive Manufacturing (AM), also known as 3D printing, have enabled the fabrication of metallic MN arrays, which offer the potential to overcome the limitations of existing systems. This review summarizes the different types of MNs used in TDD and their mode of drug delivery. The application of MNs in the treatment of a range of diseases including diabetes and cancer is discussed. The potential role of solid metallic MNs in TDD, the various techniques used for their fabrication, and the influence of their geometrical characteristics (e.g., shape, size, base diameter, thickness, and tip sharpness) on effective TDD are explored. Finally, the potential and the future directions relating to the optimization of metallic MN arrays for TDD are highlighted.
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Benchtop testing of endovascular medical devices under accurately simulated physiological conditions is a critical part of device evaluation prior to clinical assessment. Currently, glass, acrylic and silicone vascular models are predominantly used as anatomical simulator test beds for in vitro testing. However, most current models lack the ability to mimic the non-linear radial compliance of native vessels and are typically limited to being compliance-matched at a single mean pressure comparison point or not at all. Hence, a degree of caution needs to be shown when analysing results from such models under simulated physiological or pathophysiological conditions. Similarly, the clinical translation of proposed biomimetic compliance-matched vascular grafts has undoubtedly been curtailed due to performance and material limitations. Here, we propose a new design for synthetic vessels where compliance can be precisely modulated across a wide physiological pressure range by customising design parameters. Building on previously demonstrated methods of 3D printing composite compliant cylindrical structures, we demonstrate proof of principle in creating composite vascular constructs designed via a finite element model. Our constructs are 3D printable and consist of a soft silicone matrix with embedded polyurethane fibres. The fibre layer consists of circumferential sinusoidal waves with an amplitude that can be altered to result in tuneable internal radial compliances of 5.2-15.9%/mmHg × 10-2 at a mean pressure of 100 mmHg. Importantly, the design presented here allows preservation of the non-linear exponentially decaying compliance curve of native arteries and veins with an increasing mean pressure. This model offers a design toolbox for 3D printable vascular models that offer biomimetic compliance. The robust nature of this model will lead to rapidly accelerating the design process for biomimetic vascular anatomical simulators, lumped parameter model flow loops, endovascular device benchtop testbeds, and compliance-matched synthetic grafts.
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Prótese Vascular , Poliuretanos , Artérias , Complacência (Medida de Distensibilidade) , Simulação por ComputadorRESUMO
In order to develop optimum microneedle designs, researchers must first develop robust, repeatable and adaptable test methods which are representative of in vivo conditions. However, there is a lack of experimental tools which can accurately comparatively interrogate functional microneedle penetration of tissue. In this study, we seek to develop a state of the art finite element model of microneedle insertion into and penetration of human skin. The developed model employs a 3D hyperelastic, anisotropic pre-stressed multi-layered material which more accurately reflects in vivo skin conditions, while the microneedle is modeled as an array, which can capture the influence of adjacent microneedles on the overall response. Using the developed finite element model, we highlight the importance of accurate computational modeling which can decipher the mechanics of microneedle insertion, including the influence of its position within an array and how it correlates well with experimental observations. In particular, we have concluded that, for our model microneedle array, increasing skin pretension from 0 to 10% strain reduces the penetration force by 13%, ultimate local deformation about the microneedle by 22% and the ultimate penetration efficiency by 15%. We have also concluded that the presence of a base plate limits the penetration efficiency by up to 24%, while the penetration efficiency across a 5 × 1 microneedle array may vary by 27%. This model elucidates, for the first time, the combined effects of skin tension and needle geometry on accurately predicting microneedle penetration efficiency. STATEMENT OF SIGNIFICANCE: Microneedles arrays (MNAs) are medical devices with microscale protrusions, typically designed to penetrate the outermost layer of the skin, that upon optimisation, could lead to disruptive minimally-invasive disease management. However, the mechanics of MNA insertion are complex, due in part to a 'bed of nails' effect, and difficult to elucidate experimentally. Therefore, comparisons between designs, functional assessment of production batches and ultimately the likelihood of clinical translation are challenging to predict. Here, we have develop the most sophisticated in silico model of MNA insertion into pre-tensioned human skin to predict the extent of MNA penetration and therefore the likelihood of successful therapeutic delivery. Researchers can customise this model to predict the penetration efficiency of any MNA design.
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Agulhas , Pele , Administração Cutânea , Sistemas de Liberação de Medicamentos , Análise de Elementos Finitos , Humanos , MicroinjeçõesRESUMO
Medical devices, such as silicone-based prostheses designed for soft tissue implantation, often induce a suboptimal foreign-body response which results in a hardened avascular fibrotic capsule around the device, often leading to patient discomfort or implant failure. Here, it is proposed that additive manufacturing techniques can be used to deposit durable coatings with multiscale porosity on soft tissue implant surfaces to promote optimal tissue integration. Specifically, the "liquid rope coil effect", is exploited via direct ink writing, to create a controlled macro open-pore architecture, including over highly curved surfaces, while adapting atomizing spray deposition of a silicone ink to create a microporous texture. The potential to tailor the degree of tissue integration and vascularization using these fabrication techniques is demonstrated through subdermal and submuscular implantation studies in rodent and porcine models respectively, illustrating the implant coating's potential applications in both traditional soft tissue prosthetics and active drug-eluting devices.
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Próteses e Implantes , Silicones , Animais , Humanos , Teste de Materiais , Porosidade , SuínosRESUMO
The standard method of evaluating the lubricity of intermittent urinary catheters with coefficient of friction (CoF) testing is not physiologically relevant, while there is also a dearth of published research on catheter-associated urethral micro-trauma. We developed a novel human urethral epithelial cell-seeded model of the urethra to replace the rubber counter-surface used in standard CoF testing. This cell-seeded model, in conjunction with a novel testing device, allows an investigation of catheter-associated epithelial micro-trauma in vitro for the first time. The CoF of four brands of commercially-available hydrophilic-coated intermittent catheters was measured using both the rubber and urethral model counter-surfaces. Post-catheterisation of the urethral model, the damage to the epithelial layer was analysed using standard cell imaging. The rubber counter-surface was shown to over-estimate the CoF of gel-coated catheters compared to our urethral model due to stick-slip behaviour caused by polymer-on-polymer interaction of the catheter base material on the rubber counter-surface. We identified no deleterious effect due to the presence or design of catheter eyelets to either the CoF measurements or the degree of epithelium damage in our model. Furthermore, the epithelial damage did not correlate with the measured CoF of the low friction catheters, suggesting a more nuanced pathogenesis of urethral irritation and casting doubt on the translatability of a solely mechanical assessment of lubricity of urinary catheters to a clinical effect.
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Cateterismo Urinário , Cateteres Urinários , Biomimética , Fricção , Humanos , Masculino , UretraRESUMO
Pancreatic islet transplantation is a promising advanced therapy that has been used to treat patients suffering from diabetes type 1. Traditionally, pancreatic islets are infused via the portal vein, which is subsequently intended to engraft in the liver. Severe immunosuppressive treatments are necessary, however, to prevent rejection of the transplanted islets. Novel approaches therefore have focused on encapsulation of the islets in biomaterial implants which can protect the islets and offer an organ-like environment. Vascularization of the device's surface is a prerequisite for the survival and proper functioning of transplanted pancreatic islets. We are pursuing a prevascularization strategy by incorporation of vascular endothelial growth factor (VEGF)-loaded microspheres in 3-dimensional printed poly(dimethylsiloxane)-based devices prior to their prospective loading with transplanted cells. Microspheres (~50 µm) were based on poly(ε-caprolactone-PEG-ε-caprolactone)-b-poly(L-lactide) multiblock copolymers and were loaded with 10 µg VEGF/mg microspheres, and subsequently dispersed in a hyaluronic acid carrier liquid. In vitro release studies at 37°C demonstrated continuous release of fully bioactive VEGF for 4 weeks. In conclusion, our results demonstrate that incorporation of VEGF-releasing microspheres ensures adequate release of VEGF for a time window of 4 weeks, which is attractive in view of the vascularization of artificial pancreas implants.
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Indutores da Angiogênese/química , Dimetilpolisiloxanos/química , Portadores de Fármacos , Poliésteres/química , Polietilenoglicóis/química , Impressão Tridimensional , Fator A de Crescimento do Endotélio Vascular/química , Indutores da Angiogênese/farmacologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Composição de Medicamentos , Implantes de Medicamento , Liberação Controlada de Fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Ácido Hialurônico/química , Microesferas , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/farmacologiaRESUMO
Implantable tubular devices known as nerve guidance conduits (NGCs) have drawn considerable interest as an alternative to autografting in the repair of peripheral nerve injuries. At present, there exists a lack of biodegradable, biocompatible materials for the fabrication of NGCs with physical properties which suitably match the native nerve tissue. Most of the existing reports have been confined to the traditional synthetic aliphatic polyesters due to their naturally-occurring degradation by-products, suitably slow in vivo resorption timeframes and relatively diverse and tailorable range of material properties. Moreover, these thermoplastic polymers can be processed into NGCs from various methods and further tweaking of physical properties can be achieved during fabrication. Although there have been many successful reports of nerve gap repair using NGCs made from these materials, the majority have been confined to basic tubular designs across short to medium nerve gaps with at best equivalent outcomes to autografts. This article reviews the performance of poly-α-hydroxyester tubes to date (including modifications to basic hollow conduits) and is intended to aid researchers as they aim to create biomimetic NGCs capable of bridging larger nerve gaps with superior results to autografting. Based on the existing reports, a next-generation bioresorbable NGC should involve a highly flexible poly-α-hydroxyester outer tube, most suitably from a lactide-caprolactone co-polymer, with some combination of internal lumen contact guidance and bioactive neurotrophic factors. However, detailed further experimentation and an interdisciplinary approach will be required to arrive at an ideal final configuration.
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Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Regeneração Tecidual Guiada/métodos , Nervos Periféricos/efeitos dos fármacos , Poliésteres/química , Poliésteres/farmacologia , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/metabolismo , Humanos , Nervos Periféricos/citologia , Nervos Periféricos/fisiologia , Permeabilidade , Poliésteres/síntese química , Poliésteres/metabolismo , PorosidadeRESUMO
We present a simple and customizable microneedle mold fabrication technique using a low-cost desktop SLA 3D printer. As opposed to conventional microneedle fabrication methods, this technique neither requires complex and expensive manufacturing facilities nor expertise in microfabrication. While most low-cost 3D-printed microneedles to date display low aspect ratios and poor tip sharpness, we show that by introducing a two-step "Print & Fill" mold fabrication method, it is possible to obtain high-aspect ratio sharp needles that are capable of penetrating tissue. Studying first the effect of varying design input parameters and print settings, it is shown that printed needles are always shorter than specified. With decreasing input height, needles also begin displaying an increasingly greater than specified needle base diameter. Both factors contribute to low aspect ratio needles when attempting to print sub-millimeter height needles. By setting input height tall enough, it is possible to print needles with high-aspect ratios and tip radii of 20-40 µm. This tip sharpness is smaller than the specified printer resolution. Consequently, high-aspect ratio sharp needle arrays are printed in basins which are backfilled and cured in a second step, leaving sub-millimeter microneedles exposed resulting microneedle arrays which can be used as male masters. Silicone female master molds are then formed from the fabricated microneedle arrays. Using the molds, both carboxymethyl cellulose loaded with rhodamine B as well as polylactic acid microneedle arrays are produced and their quality examined. A skin insertion study is performed to demonstrate the functional capabilities of arrays made from the fabricated molds. This method can be easily adopted by the microneedle research community for in-house master mold fabrication and parametric optimization of microneedle arrays.
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Efficient and safe access to targeted therapeutic sites is a universal challenge in minimally invasive medical intervention. Percutaneous and transluminal needle insertion is often performed blindly and requires significant user skill and experience to avoid complications associated with the damage of underlying tissues or organs. Here, we report on the advancement of a safer needle with a radial mechanical clutch, which is designed to prevent overshoot injuries through the automatic stopping of the needle once a target cavity is reached. The stylet-mounted clutch system is inexpensive to manufacture and compatible with standard hypodermic or endoscopic needles, and therefore can be adapted to achieve safe access in a myriad of minimally invasive procedures, including targeted drug delivery, at-home and in-hospital intravenous access, laparoscopic and endo- and trans-luminal interventions. Here, we demonstrate the clutch needle design optimization and illustrate its potential for rapid and safe minimally invasive cannulation.
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Understanding the response of mesenchymal stem cells (MSCs) to forces in the vasculature is very important in the field of cardiovascular intervention for a number of reasons. These include the development of MSC seeded tissue engineered vascular grafts, targeted or systemic delivery of MSCs in the dynamic environment of the coronary artery and understanding the potential pathological calcifying role of mechanically conditioned multipotent cells already present in the vessel wall. In vivo, cells present in the coronary artery are exposed to the primary biomechanical forces of shear stress, radial stress and hoop stress. To date, many studies have examined the effect of these stresses in isolation, thereby not presenting the complete picture. Therefore, the main aim of this study is to examine the combined role of these stresses on MSC behaviour. To this end, a bioreactor was configured to expose MSCs seeded on flexible silicone substrates to physiological forces - namely, a pulsatile pressure between 40 and 120mmHg (5.33-1.6x10(4)Pa), radial distention of 5% and a shear stress of 10dyn/cm(2) (1Pa) at frequency of 1Hz for up to 24h. Thereafter, the 'pseudovessel' was assessed for changes in morphology, orientation and expression of endothelial and smooth muscle cell (SMC) specific markers. Hematoxylin and eosin (H&E) staining revealed that MSCs exhibit a similar mechanosensitive response to that of endothelial cells (ECs); they reorientate parallel with direction of flow and have adapted their morphology to be similar to that of ECs. However, gene expression results show the cells exhibit greater levels of SMC-associated markers alpha-smooth muscle actin and calponin (p<0.05).
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Endotélio/metabolismo , Células-Tronco Mesenquimais/citologia , Maleabilidade , Silicones , Adolescente , Adulto , Fenômenos Biomecânicos , Reatores Biológicos , Forma Celular , Células Cultivadas , Endotélio/citologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Células-Tronco Mesenquimais/metabolismo , Pessoa de Meia-Idade , RNA Mensageiro/genéticaRESUMO
Metallic-based microneedles (MNs) offer a robust platform for minimally invasive drug delivery and biosensing applications due to their mechanical strength and proven tissue and drug compatibility. However, current designs suffer from limited functional surface area or challenges in manufacturing scalability. Here, porous 316L stainless steel MN patches are proposed. Fabricated through a scalable manufacturing process, they are suitable for storage and delivery of drugs and rapid absorption of fluids for biosensing. Fabrication of these MNs involves hot embossing a patch of stainless steel-based feedstock, sintering at 1100⯰C and subsequent electropolishing. Optimisation of this manufacturing process yields devices that maintain mechanical integrity yet possess high surface area and associated porosity (36%) to maximise loading capacity. Similarly, a small pore size has been targeted (average diameter 2.22⯵m, with 90% between 1.56⯵m and 2.93⯵m) to maximise capillarity and loading efficiency. This porous network has a theoretical wicking rate of 4.7⯵l/s and can wick-up 27⯱â¯5⯵l of fluid through capillary action which allows for absorption of pharmaceuticals for delivery. When inserted into a metabolite-loaded skin model, the MNs absorbed and recovered 17⯱â¯3⯵l of the metabolite solution. The drug delivery performance of the porous metallic MNs (22.4⯱â¯4.9⯵g/cm2) was found to be threefold higher than that of topical administration (7.1⯱â¯4.3⯵g/cm2). The porous metallic MN patches have been shown to insert into porcine skin under a 19â¯N load. These results indicate the potential of design-for-manufacturing porous stainless steel MNs in biosensing and drug delivery applications. STATEMENT OF SIGNIFICANCE: Microneedles are micro-scale sharp protrusions used to bypass the stratum corneum, the skin's outer protective layer, and painlessly access dermal layers suitable for drug delivery and biosensing. Despite a depth of research in the area we have not yet seen large-scale clinical adoption of microneedle devices. Here we describe a device designed to address the potential barriers to adoption seen by other microneedles devices. We have developed a scalable, cost effective process to produce medical grade stainless steel microneedle patches which passively absorb and store drugs or interstitial fluid though a porous network and capillary action. This device, with low manufacturing and regulatory burdens may help the large-scale adoption of microneedles.
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Técnicas Biossensoriais/métodos , Sistemas de Liberação de Medicamentos/métodos , Metais/química , Agulhas , Absorção Fisico-Química , Animais , Microinjeções/instrumentação , Permeabilidade , Porosidade , Pele , Suínos , Água/químicaRESUMO
This article presents a direct additive manufacturing method for composite material soft pneumatic actuators that are capable of performing a range of programmable motions. Commonly, molding is the method used to manufacture soft fluidic actuators. This is material, labor, and time intensive and lacks the design freedom to produce custom actuators efficiently. This article proposes an alternative semiautomated method of designing and manufacturing composite soft actuators. An affordable, open-source, desktop three-dimensional (3D) printer was modified into a four-axis, combined, fused deposition modeling, and paste extrusion printer. A Grasshopper 3D algorithm was devised to implement custom actuator designs according to user inputs, resulting in a G-code print file. Bending, contracting, and twisting motion actuators were parametrically designed and subsequently additively manufactured from silicone and thermoplastic elastomer (TPE) materials. Experimental testing was completed on these actuators along with their constitutive materials. Finite element models were created to simulate the actuator's kinematic performance. Having a platform method to digitally configure and directly additively manufacture custom-motion, composite soft actuators has the potential to accelerate the development of more intricate designs and lead to potential impacts in a range of areas, including in-clinic personalization of soft assistive devices and patient-specific biomedical devices.
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Proteins are important biologic therapeutics used for the treatment of various diseases. However, owing to low bioavailability and poor skin permeability, transdermal delivery of protein therapeutics poses a significant challenge. Here, we present a new approach for transdermal protein delivery using bullet-shaped double-layered microneedle (MN) arrays with water-swellable tips. This design enabled the MNs to mechanically interlock with soft tissues by selective distal swelling after skin insertion. Additionally, prolonged release of loaded proteins by passive diffusion through the swollen tips was obtained. The bullet-shaped MNs provided an optimal geometry for mechanical interlocking, thereby achieving significant adhesion strength (~1.6Ncm-2) with rat skin. By harnessing the MN's reversible swelling/deswelling property, insulin, a model protein drug, was loaded in the swellable tips using a mild drop/dry procedure. The insulin-loaded MN patch released 60% of insulin when immersed in saline over the course of 12h and approximately 70% of the released insulin appeared to have preserved structural integrity. An in vivo pilot study showed a prolonged release of insulin from swellable MN patches, leading to a gradual decrease in blood glucose levels. This self-adherent transdermal MN platform can be applied to a variety of protein drugs requiring sustained release kinetics.
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Acrilatos/química , Diabetes Mellitus Experimental/tratamento farmacológico , Excipientes/química , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Agulhas , Poliestirenos/química , Adesivo Transdérmico , Administração Cutânea , Animais , Disponibilidade Biológica , Glicemia/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/química , Insulina/administração & dosagem , Insulina/química , Masculino , Camundongos Endogâmicos C57BL , Microinjeções , Permeabilidade , Ratos Sprague-Dawley , Pele/metabolismo , Absorção Cutânea , Distribuição TecidualRESUMO
Medical implants of fixed size cannot accommodate normal tissue growth in children, and often require eventual replacement or in some cases removal, leading to repeated interventions, increased complication rates and worse outcomes. Implants that can correct anatomic deformities and accommodate tissue growth remain an unmet need. Here, we report the design and use of a growth-accommodating device for paediatric applications that consists of a biodegradable core and a tubular braided sleeve, with inversely related sleeve length and diameter. The biodegradable core constrains the diameter of the sleeve, and gradual core degradation following implantation enables sleeve and overall device elongation in order to accommodate tissue growth. By using mathematical modeling and ex vivo experiments using harvested swine hearts, we demonstrate the predictability and tunability of the behavior of the device for disease- and patient-specific needs. We also used the rat tibia and the piglet heart valve as two models of tissue growth to demonstrate that polymer degradation enables device expansion and growth accommodation in vivo.
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With increasing knowledge of the materials science of bulk metallic glasses (BMGs) and improvements in their properties and processing, they have started to become candidate materials for biomedical devices. A dichotomy in the types of medical applications has also emerged, in which some families of BMGs are being developed for permanent devices whilst another family - of Mg-based alloys - is showing promise in bioabsorbable implants. The current status of these metallurgical and technological developments is summarized.
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Próteses e Implantes , Ligas , Materiais Biocompatíveis , Corrosão , VidroRESUMO
A series of well-designed highly branched PEG-catechol based thermo-responsive copolymers were synthesized via a one-pot RAFT polymerization. A varying degree of photocrosslinkable (meth)acrylate moieties were incorporated within the 3D structure to allow on-demand photocuring (strong cohesion, unlike conventional PEG adhesives). At the same time, multitudes of free catechol groups inspired from adhesive proteins of marine mussels were also introduced in the hyperbranched structure, giving rise to adherence to skin and cardiac tissue. The resulting ambivalent PEG-catechol based copolymers were systematically studied to investigate the effects of polymer composition on tissue bioadhesive and swelling properties, comparing acrylates to methacrylates and PEG to 2-hydroxyethyl acrylamide (HEAA). It was proved that DOPA played a major role in the adhesion performance as it significantly enhanced the adhesion performances on varied substrates. The highly branched PEG-catechol copolymers demonstrate the great potential in the design of novel surgical glues, sealants or drug delivery vectors.