Remotely Controlled Electrochemical Degradation of Metallic Implants.

Biodegradable medical implants promise to benefit patients by eliminating risks and discomfort associated with permanent implantation or surgical removal. The time until full resorption is largely determined by the implant's material composition, geometric design, and surface properties. Implants with a fixed residence time, however, cannot account for the needs of individual patients, thereby imposing limits on personalization. Here, an active Fe-based implant system is reported whose biodegradation is controlled remotely and in situ. This is achieved by incorporating a galvanic cell within the implant. An external and wireless signal is used to activate the on-board electronic circuit that controls the corrosion current between the implant body and an integrated counter electrode. This configuration leads to the accelerated degradation of the implant and allows to harvest electrochemical energy that is naturally released by corrosion. In this study, the electrochemical properties of the Fe-30Mn-1C/Pt galvanic cell model system is first investigated and high-resolution X-ray microcomputed tomography is used to evaluate the galvanic degradation of stent structures. Subsequently, a centimeter-sized active implant prototype is assembled with conventional electronic components and the remotely controlled corrosion is tested in vitro. Furthermore, strategies toward the miniaturization and full biodegradability of this system are presented.

Biodegradable, Breathable Leaf Vein-Based Tactile Sensors with Tunable Sensitivity and Sensing Range.

Resistive pressure sensors have been widely studied for application in flexible wearable devices due to their outstanding pressure-sensitive characteristics. In addition to the outstanding electrical performance, environmental friendliness, breathability, and wearable comfortability also deserve more attention. Here, a biodegradable, breathable multilayer pressure sensor based piezoresistive effect is presented. This pressure sensor is designed with all biodegradable materials, which show excellent biodegradability and breathability with a three-dimensional porous hierarchical structure. Moreover, due to the multilayer structure, the contact area of the pressure sensitive layers is greatly increased and the loading pressure can be distributed to each layer, so the pressure sensor shows excellent pressure-sensitive characteristics over a wide pressure sensing range (0.03-11.60 kPa) with a high sensitivity (6.33 kPa-1 ). Furthermore, the sensor is used as a human health monitoring equipment to monitor the human physiological signals and main joint movements, as well as be developed to detect different levels of pressure and further integrated into arrays for pressure imaging and a flexible musical keyboard. Considering the simple manufacturing process, the low cost, and the excellent performance, leaf vein-based pressure sensors provide a good concept for environmentally friendly wearable devices.

A Biodegradable Multifunctional Film as a Tissue Adhesive for Instant Hemostasis and Wound Closure.

Here, a multifunctional film (MFF) as an alternative tissue adhesive in the form of an interpenetrating network consisting of self-crosslinked aldehyde-functionalized chitosan (AC) and crosslinked poly(acrylic acid) (PAA) further coordinated with Ag+ is reported. The MFF combines enhanced toughness and stretchability, which is attributed to the synergistic effects of the double-network design. Covalent crosslinking maintains the overall integrity of the MFF matrix, while noncovalent crosslinking dissipates energy under deformation. Upon contact, the MFF quickly dries the tissue surface followed by instant physical crosslinking to the tissue. Subsequent covalent crosslinking between the aldehyde groups of the MFF and the primary amine groups on the surface of the tissue further stabilizes the adhesion. Meanwhile, Ag+ provides strong antibacterial properties to the MFF. Notably, in vivo studies demonstrate that the MFF allows facile and tough attachment to the wet and dynamic surface of rabbit liver and presents superior hemostasis and sealing properties. Furthermore, the MFF can be safely degraded without causing abnormal defects in vivo. The outstanding physicochemical properties of the MFF can potentially be a good alternative to existing sutures or staples and has potential for use in clinical practice.

Strategies for Enhancing Polyester-Based Materials for Bone Fixation Applications.

Polyester-based materials are established options, regarding the manufacturing of bone fixation devices and devices in routine clinical use. This paper reviews the approaches researchers have taken to develop these materials to improve their mechanical and biological performances. Polymer blending, copolymerisation, and the use of particulates and fibre bioceramic materials to make composite materials and surface modifications have all been studied. Polymer blending, copolymerisation, and particulate composite approaches have been adopted commercially, with the primary focus on influencing the in vivo degradation rate. There are emerging opportunities in novel polymer blends and nanoscale particulate systems, to tune bulk properties, and, in terms of surface functionalisation, to optimise the initial interaction of devices with the implanted environment, offering the potential to improve the clinical performances of fracture fixation devices.

Current status of biobased and biodegradable food packaging materials: Impact on food quality and effect of innovative processing technologies.

Fossil-based plastic materials are an integral part of modern life. In food packaging, plastics have a highly important function in preserving food quality and safety, ensuring adequate shelf life, and thereby contributing to limiting food waste. Meanwhile, the global stream of plastics into the oceans is increasing exponentially, triggering worldwide concerns for the environment. There is an urgent need to reduce the environmental impacts of packaging waste, a matter raising increasing consumer awareness. Shifting part of the focus toward packaging materials from renewable resources is one promising strategy. This review provides an overview of the status and future of biobased and biodegradable films used for food packaging applications, highlighting the effects on food shelf life and quality. Potentials, limitations, and promising modifications of selected synthetic biopolymers; polylactic acid, polybutylene succinate, and polyhydroxyalkanoate; and natural biopolymers such as cellulose, starch, chitosan, alginate, gelatine, whey, and soy protein are discussed. Further, this review provides insight into the connection between biobased packaging materials and innovative technologies such as high pressure, cold plasma, microwave, ultrasound, and ultraviolet light. The potential for utilizing such technologies to improve biomaterial barrier and mechanical properties as well as to aid in improving overall shelf life for the packaging system by in-pack processing is elaborated on.

Safety and efficacy of sFilm-FS, a novel biodegradable fibrin sealant, in Göttingen minipigs.

Bleeding during surgical procedures is a common complication. Therefore, hemostatic agents have been developed to control bleeding, and fibrin sealants have several benefits. sFilm-FS is a novel fibrin sealant that comprises a biodegradable co-polymeric film embedded with human fibrinogen and thrombin. Herein, the safety and efficacy of sFilm-FS were compared using a liver and spleen puncture model of Göttingen minipigs with those of the standard hemostatic techniques (control animals) and EVARREST®, a reference fibrin sealant. Hemostasis and reduced blood loss were more effectively achieved with sFilm-FS than with the standard techniques in the control animals and comparable to those achieved with EVARREST®. No treatment-related adverse effects were observed in any of the groups. Histopathological evaluation indicated that sFilm-FS was slightly and moderately reactive at the liver puncture site and spleen, respectively, compared with the standard techniques in the control animals. These changes are expected degradation reactions of the co-polymeric film and are not considered as adverse events. No treatment-related abnormalities were noted in the other evaluated organs. Additionally, no evidence of local or systemic thromboses was noted. These results support the use of sFilm-FS for hemostasis in humans.

Local Tolerance and Biodegradability of a Novel Artificial Dura Mater Graft Following Implantation Onto a Dural Defect in Rabbits.

Dura mater defects are a common problem following neurosurgery. Dural grafts are used to repair these defects; among them are biodegradable polymeric synthetic grafts. ArtiFascia is a novel synthetic and fibrous Dural graft, composed of poly(l-lactic-co-caprolactone acid) (PLCL) and poly(d-lactic-co-caprolactone acid). In this study, the biodegradability and local tolerance of ArtiFascia was evaluated in rabbits and compared with a bovine collagen matrix as a reference control. ArtiFascia implantation resulted in the formation of neo-dura at the site of implantation and recovery of the dural damage and the calvaria bone above. The implanted graft was completely absorbed after 12 months and the remaining macrophages were morphologically consistent with the anti-inflammatory M2-like phenotype, which contributes to tissue healing and are not pro-inflammatory. The site of the drilled skull bone had a continuous smooth surface, without exuberant tissue or inflammation and a newly formed trabecular bone formation indicated the healing process of the bone. These results support the local tolerability and biodegradability of ArtiFascia when used as a dural graft in rabbits. This study suggests that PLCL-based grafts including ArtiFascia are safe and effective to repair Rabbit Dura.

Biocompatible and totally disintegrable semiconducting polymer for ultrathin and ultralightweight transient electronics.

Increasing performance demands and shorter use lifetimes of consumer electronics have resulted in the rapid growth of electronic waste. Currently, consumer electronics are typically made with nondecomposable, nonbiocompatible, and sometimes even toxic materials, leading to serious ecological challenges worldwide. Here, we report an example of totally disintegrable and biocompatible semiconducting polymers for thin-film transistors. The polymer consists of reversible imine bonds and building blocks that can be easily decomposed under mild acidic conditions. In addition, an ultrathin (800-nm) biodegradable cellulose substrate with high chemical and thermal stability is developed. Coupled with iron electrodes, we have successfully fabricated fully disintegrable and biocompatible polymer transistors. Furthermore, disintegrable and biocompatible pseudo-complementary metal-oxide-semiconductor (CMOS) flexible circuits are demonstrated. These flexible circuits are ultrathin (<1 µm) and ultralightweight (∼2 g/m2) with low operating voltage (4 V), yielding potential applications of these disintegrable semiconducting polymers in low-cost, biocompatible, and ultralightweight transient electronics.

Biopolymers as Food Packaging Materials.

Oil-derived plastics are the most commonly used materials for packaging because of their features, low cost, and availability of resources for manufacturing [...].

A state-of-art review on antenna designs for ingestible application.

Research interest in ingestible Wireless Capsule Endoscopy (WCE) studies in humans showed better results than conventional invasive probe endoscopy methods. Because of the structure and the position of the small intestine, proper scanning cannot be done in the area using traditional endoscopic methods. For patient comfort, continuous developments have been suggested in capsule endoscopy designs in terms of the quality of images transmitted, capsule orientation, positioning of the capsule from outside the body, link budget analysis, impedance matching and capsule miniaturization. To improve the image quality, transmission efficiency of the antenna has to be improved. This has led to the development of many antenna structures in an ingestible capsule system. Literatures have identified Med Radio and ISM (Industrial, Scientific and Medical) band as operation bands for the WCE systems. This review aims to highlight: (1) design considerations for various antenna types, (2) miniaturization techniques, (3) operating bands, specifications and various design challenges and (4) research gap, advanced design technologies and targets of ingestible antenna system. The main aim of this paper is to tutorial the up-to-date information on the recent antenna designing techniques and challenges for ingestible system.

Microstructured Photo-Crosslinked Poly(Trimethylene Carbonate) for Use in Soft Lithography Applications: A Biodegradable Alternative for Poly(Dimethylsiloxane).

Photo-crosslinkable poly(trimethylene carbonate) (PTMC) macromers were used to fabricate microstructured surfaces. Microstructured PTMC surfaces were obtained by hot embossing the macromer against structured silicon masters and subsequent photo-crosslinking, resulting in network formation. The microstructures of the master could be precisely replicated, limiting the shrinkage. Microstructured PTMC was investigated for use in two different applications: as stamping material to transfer a model protein to another surface and as structured substrate for cell culture. Using the flexible and elastic materials as stamps, bovine serum albumin labelled with fluorescein isothiocyanate was patterned on glass surfaces. In cell culture experiments, the behavior of human mesenchymal stem cells on nonstructured and microstructured PTMC surfaces was investigated. The cells strongly adhered to the PTMC surfaces and proliferated well. Compared to poly(dimethylsiloxane) (PDMS), which is commonly used in soft lithography, the PTMC networks offer significant advantages. They show better compatibility with cells, are biodegradable, and have much better mechanical properties. Both materials are transparent, flexible, and elastic at room temperature, but the tear resistance of PTMC networks is much higher than that of PDMS. Thus, PTMC might be an alternative material to PDMS in the fields of biology, medicine, and tissue engineering, in which microfabricated devices are increasingly being applied.

Evaluation of Infection Resistance of Biodegradable versus Conventional Annuloplasty Rings in an in vivo Rat Subcutaneous Model.

BACKGROUND: Biodegradable atrioventricular annuloplasty rings are theoretically more infection resistant due to their intra-annular implantation technique and nonporous structures (monofilament of poly-1,4-dioxanone). The aim of this study was to investigate the infection resistance of a biodegradable annuloplasty ring (Kalangos-Bioring®) in a rat subcutaneous implantation model and to compare it with a commonly used conventional annuloplasty ring (Edwards Physio II®). METHODS: This study included 32 Wistar albino rats which were divided into 2 groups according to the implantation of sterile or infected annuloplasty rings as control and study groups. Each animal had 2 implantation pockets (made on the right and left side of the dorsal median line) where 1 cm of the biodegradable annuloplasty ring was implanted into one pocket and 1 cm of the conventional annuloplasty ring was implanted into the other pocket. The infection model was created by topical inoculation of 1 mL Staphylococcus aureus strain (2 × 107 colony-forming units/mL) into the implantation pockets before skin closure. Each group was equally divided into 4 subgroups according to different follow-up schedules. The animals were inspected for local as well as systemic infection signs, and the rings were explanted at weeks 2, 4, 9, and 14 following implantation. Implantation pockets were evaluated macroscopically as well as by histopathological examinations. Microbiological analysis of the explanted implants with surrounding tissue was done by using quantitative sonication method. RESULTS: Conventional ring-implanted pockets showed a more prominent inflammation reaction than the biodegradable ring-implanted pockets, and this characteristic was found to be accentuated with bacterial contamination. The sterile rings did not reveal any positive cultures in either group. The number of positive cultures found in conventional rings contaminated with S. aureus was greater than in the biodegradable ring group (11/16 vs. 2/16 positive cultures, respectively; p = 0.0032). The amounts of growing bacteria in the culture environment were also statistically significantly higher in the conventional ring group (7,175 ± 5,936 vs. 181 ± 130 colony-forming units/mL, respectively; p < 0.0005). CONCLUSIONS: This is the first experimental study confirming the theoretical advantage of the infection resistance of the biodegradable annuloplasty ring (Kalangos-Bioring®) when implanted in an active infectious environment. Large animal models mimicking clinical scenarios and clinical comparative studies are needed to verify our results.

Bioresorbable vascular scaffolds: Biodegradation, drug delivery and vascular remodeling.

The metallic stents with durable polymers have been effective in reducing the need for revascularization, but the permanent presence of the metal and polymer have been associated with persistent inflammation, hypersensitivity reactions and incidence of thrombosis. Recent innovations of bioresorbable polymers are in development which could serve as temporary scaffolds that degrade into molecules and eventually resorb overtime, and leave the artery free of any permanent prosthetic constraints. The transient scaffolding has the advantages of restoring blood vessel to natural state, improve vasomotor tone and increase lumen enlargement because of expansive remodeling following completion of polymer resorption. The success of bioresorbable vascular scaffolds will depend on the degradation timeline, such that the elastic recoil of the blood vessel and negative remodeling which could potentially lead to restenosis are prevented. Bioresorbable scaffolds with bulky backbone and thick struts could lead to prolonged biodegradation, alter blood flow dynamics and increase thrombogenicity. The development of bioresorbable scaffolds is challenging because of the complexity of finding an ideal balance of polymer biodegradation and controlled drug release over time, such that the fractional drug released achieves optimal inhibitory concentration until the blood vessel remodels to a stable set point. This review discusses the various types of biodegradable materials, factors affecting biodegradation, drug release kinetics, vascular biocompatibility, adaptive vascular remodeling, and challenges in the development of bioresorbable scaffolds to treat vascular restenosis.

Preclinical Safety Evaluation in Rats of a Polymeric Matrix Containing an siRNA Drug Used as a Local and Prolonged Delivery System for Pancreatic Cancer Therapy.

Conventional chemotherapy treatments for pancreatic cancer are mainly palliative. RNA interference (RNAi)-based drugs present the potential for a new targeted treatment. LOcal Drug EluteR (LODER(TM)) is a novel biodegradable polymeric matrix that shields drugs against enzymatic degradation and releases small interfering RNA (siRNA) against G12D-mutated KRAS (siG12D). siG12D-LODER has successfully passed a phase 1/2a clinical trial. Such a formulation necessitates biocompatibility and safety studies. We describe the safety and toxicity studies with siG12D-LODER in 192 Hsd:Sprague Dawley rats, after repeated subcutaneous administrations (days 1, 14, and 28). Animals were sacrificed on days 29 and 42 (recovery phase). In all groups, no adverse effects were noted, and all animals showed favorable local and systemic tolerability. Histopathologically, LODER implantation resulted in the expected capsule formation, composed of a thin fibrotic tissue. On the interface between the cavity and the capsule, a single layer composed of macrophages and multinucleated giant cells was observed. No difference was noted between the placebo and siG12D-LODER groups. These findings provide valuable information for future preclinical studies with siRNA-bearing biodegradable polymers and for the safety aspects of RNAi-based drugs as a targeted therapy.

Enhanced mechanical properties and increased corrosion resistance of a biodegradable magnesium alloy by plasma electrolytic oxidation (PEO).

We report the enhanced mechanical properties of AZ31 magnesium alloys by plasma electrolytic oxidation (PEO) coating in NaOH, Na2SiO3, KF and NaH2PO4·2H2O containing electrolytes. Mechanical properties including wear resistance, surface hardness and elastic modulus were increased for PEO-coated AZ31 Mg alloys (PEO-AZ31). DC polarization in Hank's solution indicating that the corrosion resistance significantly increased for PEO-coating in KF-contained electrolyte. Based on these results, the PEO coating method shows promising potential for use in biodegradable implant applications where tunable corrosion and mechanical properties are needed.

Long-term Local and Systemic Safety of Poly(L-lactide-co-epsilon-caprolactone) after Subcutaneous and Intra-articular Implantation in Rats.

The use of biodegradable materials is gaining popularity in medicine, especially in orthopedic applications. However, preclinical evaluation of biodegradable materials can be challenging, since they are located in close contact with host tissues and might be implanted for a long period of time. Evaluation of these compounds requires biodegradability and biocompatibility studies and meticulous pathology examination. We describe 2 preclinical studies performed on Sprague-Dawley rats for 52 weeks, to evaluate clinical pathology, biocompatibility, biodegradability, and systemic toxicity after implantation of 2-layered films or saline-inflated balloon-shaped implants of downsized InSpace™ devices (termed "test device"). The test devices are made from a copolymer of poly-L-lactide-co-∊-caprolactone in a 70:30 ratio, identical to the device used in humans, intended for the treatment of rotator cuff tears. Intra-articular film implantation and subcutaneous implantation of the downsized device showed favorable local and systemic tolerability. Although the implanted materials have no inherent toxic or tumorigenic properties, one animal developed a fibrosarcoma at the implantation site, an event that is associated with a rodent-predilection response where solid materials cause mesenchymal neoplasms. This effect is discussed in the context of biodegradable materials along with a detailed description of expected pathology for biodegradable materials in long-term rodent studies.

Permeation measurement of gestodene for some biodegradable materials using Franz diffusion cells.

Biodegradable poly(d,l-lactide) (PDLLA), Poly(trimethylene carbonate) (PTMC), polycaprolactone (PCL), poly(caprolactone-co-d,l-lactide) (PCDLLA) and poly(trimethylene carbonate-co-caprolactone) (PTCL) are recently used for clinical drug delivery system such as subcutaneous contraceptive implant capsule due to their biodegradable properties that they could possess long-term stable performance in vivo without removal, however their permeation rate is unknown. In the work, biodegradable material membranes were prepared by solvent evaporation using chloroform, and commercial silicone rubber membrane served as a control. Gestodene was used as a model drug. Gestodene has high biologic progestational activity which allows for high contraceptive reliability at very low-dose levels. The permeation rate of gestodene for several biodegradable materials was evaluated. In vitro diffusion studies were done using Franz diffusion cells with a diffusion area of 1.33 cm(2). Phosphate buffer solution (PBS, pH 7.4), 10% methanol solution and distilled water were taken in donor and receiver chambers at temperature of 37 °C respectively. The in vitro experiments were conducted over a period of 24 h during which samples were collected at regular intervals. The withdrawn samples were appropriately diluted and measured on UV-vis spectrophotometer at 247 nm. Conclusion data from our study showed that permeation rate of PCDLLA with CL ratio more than 70% could be more excellent than commercial silicone rubber membrane. They may be suitable as a candidate carrier for gestodene subcutaneous contraceptive implants in contraceptive fields.

Inhibition of 3-D tumor spheroids by timed-released hydrophilic and hydrophobic drugs from multilayered polymeric microparticles.

First-line cancer chemotherapy necessitates high parenteral dosage and repeated dosing of a combination of drugs over a prolonged period. Current commercially available chemotherapeutic agents, such as Doxil and Taxol, are only capable of delivering single drug in a bolus dose. The aim of this study is to develop dual-drug-loaded, multilayered microparticles and to investigate their antitumor efficacy compared with single-drug-loaded particles. Results show hydrophilic doxorubicin HCl (DOX) and hydrophobic paclitaxel (PTX) localized in the poly(dl-lactic-co-glycolic acid, 50:50) (PLGA) shell and in the poly(l-lactic acid) (PLLA) core, respectively. The introduction of poly[(1,6-bis-carboxyphenoxy) hexane] (PCPH) into PLGA/PLLA microparticles causes PTX to be localized in the PLLA and PCPH mid-layers, whereas DOX is found in both the PLGA shell and core. PLGA/PLLA/PCPH microparticles with denser shells allow better control of DOX release. A delayed release of PTX is observed with the addition of PCPH. Three-dimensional MCF-7 spheroid studies demonstrate that controlled co-delivery of DOX and PTX from multilayered microparticles produces a greater reduction in spheroid growth rate compared with single-drug-loaded particles. This study provides mechanistic insights into how distinctive structure of multilayered microparticles can be designed to modulate the release profiles of anticancer drugs, and how co-delivery can potentially provide better antitumor response.

Synthesis, characterization and antibacterial activity of biodegradable films prepared from Schiff bases of zein.

Pure zein is known to be very hydrophobic, but is still inappropriate for coating and film applications because of their brittle nature. In an attempt to improve the flexibility and the antimicrobial activity of these coatings and films, Chemical modification of zein through forming Schiff bases with different phenolic aldhydes was tried. Influence of this modifications on mechanical, topographical, wetting properties and antimicrobial activity of zein films were evaluated. The chemical structure of the Schiff bases films were characterized by ATR-FTIR spectroscopy. The results indicate an improvement in mechanical properties with chemically modification of zein to form Schiff bases leading to a reduction in the elastic modulus. An increase in the elongation at break has been observed, but with slight influence on tensile strength. Plasticized zein films have similar initial contact angle (∼40°). An increase in reaction temperature and time increases film's affinity towards water. As shown by contact angle measurements, a noticeable relation was found between film composition and the hydrophilicity. Surface topography also varied by forming Schiff bases, becoming rougher than zein-based films. The antibacterial activities of zein and Schiff bases of zein-based films were investigated against gram-positive bacteria (Listeria innocua, Listeria monocytogenes, Bacillus cereus and Clostridium sporogenes) and gram-negative bacteria (Escherichia coli, Yersinia enterocolitica and Salmonella enterica). It was found that the antibacterial activity of the Schiff bases-based films was more effective than that of zein-based films.

Antimicrobial, Antioxidant, and Anti-Inflammatory Nanoplatform for Effective Management of Infected Wounds.

Burn wound healing continues to pose significant challenges due to excessive inflammation, the risk of infection, and impaired tissue regeneration. In this regard, an antibacterial, antioxidant, and anti-inflammatory nanocomposite (called HPA) that combines a nanosystem using hexachlorocyclotriphosphazene and the natural polyphenol of Phloretin with silver nanoparticles (AgNPs) is developed. HPA effectively disperses AgNPs to mitigate any toxicity caused by aggregation while also showing the pharmacological activities of Phloretin. During the initial stage of wound healing, HPA rapidly releases silver ions from its surface to suppress bacterial activity. Moreover, these nanoparticles are pH-sensitive and degrade efficiently in the acidic infection microenvironment, gradually releasing Phloretin. This sustained release of Phloretin helps scavenge overexpressed reactive oxygen species in the infected microenvironment area, thus reducing the upregulation of pro-inflammatory cytokines. The antibacterial activity, free radical clearance, and regulation of inflammatory factors of HPA through in vitro experiments are validated. Additionally, its effects using an infectious burn mouse model in vivo are evaluated. HPA is found to promote collagen deposition and epithelialization in the wound area. With its synergistic antibacterial, antioxidant, and anti-inflammatory activities, as well as favorable biocompatibilities, HPA shows great promise as a safe and effective multifunctional nanoplatform for burn injury wound dressings.