[Research progress on medical devices of polyhydroxyalkanoate in orthopedics].

Objective: To review the research progress of natural biomaterial polyhydroxyalkanoate (PHA) in orthopedics. Methods: The literature concerning PHA devices for bone defects, bone repair, and bone neoplasms, respectively, in recent years was extensively consulted. The three aspects of the advantages of PHA in bone repair, the preparation of PHA medical devices for bone repair and their application in orthopedics were discussed. Results: Due to excellent biodegradability, biocompatibility, and potential osteoinduction, PHA is a kind of good bone repair material. In addition to the traditional PHA medical implants, the use of electrostatic spinning and three-dimensional printing can be designed to various functional PHA medical devices, in order to meet the orthopedic clinical demands, including the bone regeneration, minimally invasive bone tissue repair by injection, antibacterial bone repair, auxiliary establishment of three-dimensional bone tumor model, directed osteogenic differentiation of stem cells, etc. Conclusion: At present, PHA is a hotspot of biomaterials for translational medicine in orthopedics. Although they have not completely applied in the clinic, the advantages of repair in bone defects have been gradually reflected in tissue engineering, showing an application prospect in orthopedics.

Polyhydroxyalkanoates and their advances for biomedical applications.

Polyhydroxyalkanoates (PHAs) are sustainable, versatile, biocompatible, and bioresorbable polymers that are suitable for biomedical applications. Produced via bacterial fermentation under nutrient-limiting conditions, they are uncovering a new horizon for devices in biomedical applications. A wide range of cell types including bone, cartilage, nerve, cardiac, and pancreatic cells, readily attach grow and are functional on PHAs. The tuneable physical properties and resorption rates of PHAs provide a toolbox for biomedical engineers in developing devices for hard and soft tissue engineering applications and drug delivery. The versatility of PHAs and the vast range of different PHA-based prototypes are discussed. Current in vitro, ex vivo, and in vivo development work are described and their regulatory approvals are reviewed.

Recent Progress in Polyhydroxyalkanoates-Based Copolymers for Biomedical Applications.

In recent years, naturally biodegradable polyhydroxyalkanoate (PHA) monopolymers have become focus of public attentions due to their good biocompatibility. However, due to its poor mechanical properties, high production costs, and limited functionality, its applications in materials, energy, and biomedical applications are greatly limited. In recent years, researchers have found that PHA copolymers have better thermal properties, mechanical processability, and physicochemical properties relative to their homopolymers. This review summarizes the synthesis of PHA copolymers by the latest biosynthetic and chemical modification methods. The modified PHA copolymer could greatly reduce the production cost with elevated mechanical or physicochemical properties, which can further meet the practical needs of various fields. This review further summarizes the broad applications of modified PHA copolymers in biomedical applications, which might shred lights on their commercial applications.

Polyester as Antigen Carrier toward Particulate Vaccines.

Spherical polyhydroxyalkanoate (PHA) inclusions are naturally self-assembled inside bacteria. These PHA beads are shell-core structures composed of a hydrophobic PHA core surrounded by proteins, such as PHA synthase (PhaC). PhaC is covalently attached and serves as an anchor protein for foreign protein vaccine candidate antigens. PHA beads displaying single and multiple antigens showed enhanced immunological properties when compared to respective soluble vaccines. This review highlights the unique design space of the PHA bead-based vaccines toward the development of safe and synthetic particulate vaccines. The PHA bead technology will be compared with chemically synthesized polyesters, such as polylactic acids, formulated to deliver vaccine antigens. The performance of PHA bead vaccine candidates to induce specific immune responses and protective immunity against bacterial and viral pathogens in animal trials will be summarized. We propose that the PHA bead technology offers a versatile vaccine platform for design and cost-effective manufacture of synthetic multivalent vaccines.

Recent progress in the utilization of biosynthesized polyhydroxyalkanoates for biomedical applications - Review.

PHAs (polyhydroxyalkanoates) have emerged as biodegradable plastics more strongly in the 20th century. A wide range of bacterial species along with fungi, plants, oilseed crops and carbon sources have been used extensively to synthesize PHA on large scales. Alteration of PHA monomers in their structures and composition has led to the development of biodegradable and biocompatible polymers with highly specific mechanical properties. This leads to the incorporation of PHA in numerous biomedical applications within the previous decade. PHAs have been fabricated in various forms to perform tissue engineering to repair liver, bone, cartilage, heart tissues, cardiovascular tissues, bone marrow, and to act as drug delivery system and nerve conduits. A large number of animal trials have been carried out to assess the biomedical properties of PHA monomers, which also confirms the high compatibility of PHA family for this field. This review summarizes the synthesis of PHA from different sources, and biosynthetic pathways and biomedical applications of biosynthesized polyhydroxyalkanoates.

Sustratos electrohilados de poli(hidroxibutirato-co-hidroxihexanoato) con glicósidos para reparación de la lesión medular / Glycosides-bearing electrospun poly(hydroxybutyrate-co-hydroxyhexanoate) substrates for the repair of injured spinal cord

Objetivo: Obtención mediante electrohilado de fibras micro- y submicrométricas de poliésteres funcionalizadas con glicósidos que constituyen elementos estructurales de proteoglicanos, para su uso en la reparación del tejido medular. Material y métodos: Las fibras se prepararon a partir de disoluciones de poli(3-hidroxibutirato-co-3-hidroxihexanoato) con glicósidos sintéticos mediante electrohilado variando sistemáticamente las condiciones del proceso. La morfología de las fibras fue analizada mediante microscopía electrónica de barrido. Asimismo, se evaluó la estabilidad de la interacción entre el glicósido y la fibra en medio acuoso, y su toxicidad en cultivos de células neurales. Resultados: La morfología de las fibras obtenidas depende principalmente de los parámetros de la disolución. En medio acuoso, el glicósido sulfatado se liberó de las fibras más lentamente que el que no tenía dicho grupo funcional. La viabilidad de las células neurales no se vio afectada por los glicósidos. Conclusión: La preparación de microfibras alineadas de poliéster funcionalizadas con glicósidos es posible. La mayor parte del glicósido permanece retenido en las fibras sumergidas en agua después de varios días. El electrohilado es una técnica muy accesible y versátil para la fabricación de soportes en estrategias de terapia celular de lesiones medulares (AU)

Objective: Preparation of functionalized micro- and submicrofibers by electrospinning of polyesters with glycosides which are structural elements of proteoglycans, for application to the repair of spinal cord lesions. Material and methods: Solutions of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) with synthetic glycosides were prepared varying systematically the processing conditions. Fiber morphology assessed by scanning electron microscopy. The stability of the interaction between the glycoside and the polymer fiber was evaluated in aqueous medium, and their toxicity in cultures of neural cells. Results: The fiber morphology was altered mainly by the solution parameters. In aqueous medium, the glycoside with a sulfate group was released from fibers at slower rate than the non-sulfated glycoside. The viability of neural cells was not affected by the glycosides. Conclusion: It is possible to fabricate aligned polyester micro fibers with glycosides. Most of the glycoside present in the fibers remains in the substrate after extraction in water for several days. Electrospinning is a very accessible and versatile technique for application to strategies of cellular therapy in spinal cord injuries (AU)

Novel particulate vaccines utilizing polyester nanoparticles (bio-beads) for protection against Mycobacterium bovis infection - a review.

Bovine tuberculosis (TB) continues to be a major health problem in cattle and development of a safe effective vaccine to control TB in cattle would be very useful. This paper reviews progress and provides new data in development of a TB bio-bead vaccine based on polyester nanoparticle inclusions which were produced by bioengineered bacteria. Polyhydroxybutyrate (PHB) biopolyester nanoparticles (bio-beads) have been produced which displayed mycobacterial antigens, Ag85A and ESAT-6, on the surface of the bio-beads for use as vaccines for the control of tuberculosis. Bio-beads were purified from the host production bacteria, Escherichia coli and the generally regarded as safe (GRAS) bacterium, Lactococcus lactis. Previous published studies showed that vaccination with Ag85A/ESAT-6 bio-beads induced antigen-specific IFN-γ, IL-17A, IL-6, TNF-α and IL-2 in splenocytes, but no significant increase in IL-4, IL-5 or IL-10. New results showed that antigen-specific IFN-γ release was induced by both CD4 and CD8 T cells in mice vaccinated with the Ag85A/ESAT-6 bio-beads. Mice vaccinated with Ag85A/ESAT-6 bio-beads alone or in combination with BCG had significantly lower bacterial counts from the lungs and spleen following aerosol challenge with Mycobacterium bovis compared to control groups. This unique approach to the design and production of bacterial-derived bio-beads displaying antigens enables a cost-effective way to express a diverse antigen repertoire for use as vaccines to combat TB or other diseases.

Biofunctionalization of polymers and their applications.

Polyhydroxyalkanoates (PHAs) are a family of biopolyesters synthesized by many types of bacteria as carbon and energy reserve materials. PHAs combine properties of thermal processibility, biodegradability, biocompatibility and sustainability. They have attracted attention from fermentation, materials and biomedical industries. Recent environmental concerns such as CO(2) emissions and plastic pollution as well as rapid exhaustion of petroleum resources have increased public and industrial interests in these unique materials. In fact, PHA has slowly evolved into an industrial value chain ranging from microbial fermentation, bioplastic packaging, biofuel, medical implants, drug delivery, protein purification, chiral chemicals and drug development. This chapter will discuss microbial PHA production and its applications in various fields.

Evaluation of a cationic poly(ß-hydroxyalkanoate) as a plasmid DNA delivery system.

Poly(ß-hydroxyalkanoates) (PHAs) are biodegradable polymers produced by a wide range of bacteria. The structures of these polymers may be tuned by controlling the available carbon source composition, but the range of functional groups accessible in this manner is limited to those that the organism is able to metabolize. Much effort has been made to chemically modify the side chains of these polymers to achieve new materials with new applications. We have previously reported the synthesis of the first cationic PHA, poly(ß-hydroxyoctanoate)-co-(ß-hydroxy-11-(bis(2-hydroxyethyl)-amino)-10-hydroxyundecanoate) (PHON). Here, we report the use of this polymer as a plasmid DNA delivery system. PHON was found to bind and condense the DNA into positively charged particles smaller than 200 nm. In this manner, PHON was shown to protect plasmid DNA from nuclease degradation for up to 30 min. In addition, treatment of mammalian cells in vitro with PHON/DNA complexes resulted in luciferase expression as the result of the delivery of the encoded gene.

Medical application of microbial biopolyesters polyhydroxyalkanoates.

Polyhydroxyalkanoates (PHA) are a family of polyesters synthesized by microorganisms under unbalanced growth conditions. PHA including poly-3-hydroxybutyrate (PHB), copolymers of 3-hydroxybutyrate and 3-hydroxyvalerate (PHBV), poly-4-hydroxybutyrate (P4HB), copolymers of 3-hydroxybutyrate and 3-hydroxyhexanoate (PHBHHx), and poly-3-hydroxyoctanoate (PHO) are now available in sufficient quantity for tissue engineering medical application studies due to their reasonable biocompatibility, adjustable mechanical properties, and controllable biodegradability. This paper reviews many achievements based on PHA for medical devices development, tissue repair, artificial organ construction, drug delivery, and nutritional/therapeutic uses. Combined with the recent FDA approval for P4HB clinical application, one can expect a good prospect for PHA application in the medical fields.