Superhydrophobic Polyhydroxyalkanoates: Preparation and Applications.

Poly( R-3-hydroxybutyrate- co- R-3-hydroxyhexanoate) (PHBHHx), a family member of microbial polyhydroxyalkanoates (PHA), is a biodegradable and biocompatible material with some hydrophobicity and reasonable strength for packaging and tissue engineering applications. In this study, superhydrophobic PHBHHx is fabricated via a simple nonsolvent-assisted process. The material can absorb all tested hydrophobic solvents and oil up to 6-fold of the material weights from water, permitting applications for cleaning environmental oil or solvent pollutions with convenience of disposal after the usage due to its biodegradability. With an excellent combination of biodegradability and biocompatibility, superhydrophobic PHBHHx films are evaluated for antibioadhesion properities to exploit possible implant usages. Up to 100% reductions for platelet adhesions on the superhydrophobic PHBHHx surfaces are observed compared with that on the control material surfaces. Superhydrophobic biodegradable and biocompatible PHBHHx films demonstrate promising low value and high volume or high value and low volume applications.

Highly Efficient Fluorescent Material Based on Rare-Earth-Modified Polyhydroxyalkanoates.

Fluorescent materials play an important role in biomedical fields. However, the main types of fluorescent materials suffer from several disadvantages especially the biotoxicity, which largely restrict its wider applications in biological fields. In this study, a highly efficient rare-earth-modified fluorescent material was successfully designed and fabricated based on polyhydroxyalkanoates, which are known as biodegradable and biocompatible materials. A new Functional-PHA polymer was microbially synthesized by engineered Halomonas bluephagenesis and was used as a basal matrix to generate the rare-earth-modified PHA. N-Acetyl-l-cysteine-grafted PHA (NAL-grafted-PHA) was first produced via a UV-initiated thiol-ene click reaction and the rare earth metal ions (Eu3+ and Tb3+) were subsequently chelated onto the NAL-grafted-PHA through the coordination effect. The composite material exhibited intense photoluminescence properties under UV laser excitation, indicating the excellent features as fluorescent material. The enhanced hydrophilicity and superior biocompatibility of rare-earth-chelated PHA were confirmed, suggesting its great potential application value in biomedical fields.

Synthesis, Characterization and Application of Thermoresponsive Polyhydroxyalkanoate-graft-Poly(N-isopropylacrylamide).

A thermoresponsive graft copolymer polyhydroxyalkanoate-g-poly(N-isopropylacrylamide) or short as PHA-g-PNIPAm, was successfully synthesized via a three-step reaction. First, PNIPAm oligomer with a trithiocarbonate-based chain transfer agent (CTA), short as PNIPAm-CTA, with designed polymerization degree was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Subsequently, the PNIPAm-CTA was treated with n-butylamine for aminolysis in order to obtain a pendant thiol group at the end of the chain (PNIPAm-SH). Finally, the PNIPAm-SH was grafted onto unsaturated P(3HDD-co-3H10U), a random copolymer of 3-hydroxydodecanoate (3HDD) and 3-hydroxy-10-undecylenate (3H10U), via a thiol-ene click reaction. Enhanced hydrophilicity and thermoresponsive property of the resulted PHA-g-PNIPAm were confirmed by water contact angle studies. The biocompatibility of PHA-g-PNIPAm was comparable to poly-3-hydroxybutyrate (PHB). The graft copolymer PHA-g-PNIPAm based on biopolyester PHA could be a promising material for biomedical applications.

Polyhydroxyalkanoates: the natural biopolyester for future medical innovations.

Polyhydroxyalkanoates (PHAs) are a family of natural microbial biopolyesters with the same basic chemical structure and diverse side chain groups. Based on their excellent biodegradability, biocompatibility, thermoplastic properties and diversity, PHAs are highly promising medical biomaterials and elements of medical devices for applications in tissue engineering and drug delivery. However, due to the high cost of biotechnological production, most PHAs have yet to be applied in the clinic and have only been studied at laboratory scale. This review focuses on the biosynthesis, diversity, physical properties, biodegradability and biosafety of PHAs. We also discuss optimization strategies for improved microbial production of commercial PHAs via novel synthetic biology tools. Moreover, we also systematically summarize various medical devices based on PHAs and related design approaches for medical applications, including tissue repair and drug delivery. The main degradation product of PHAs, 3-hydroxybutyrate (3HB), is recognized as a new functional molecule for cancer therapy and immune regulation. Although PHAs still account for only a small percentage of medical polymers, up-and-coming novel medical PHA devices will enter the clinical translation stage in the next few years.

Biomimetic natural biomaterials for tissue engineering and regenerative medicine: new biosynthesis methods, recent advances, and emerging applications.

Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering (TE) and regenerative medicine. In contrast to conventional biomaterials or synthetic materials, biomimetic scaffolds based on natural biomaterial can offer cells a broad spectrum of biochemical and biophysical cues that mimic the in vivo extracellular matrix (ECM). Additionally, such materials have mechanical adaptability, microstructure interconnectivity, and inherent bioactivity, making them ideal for the design of living implants for specific applications in TE and regenerative medicine. This paper provides an overview for recent progress of biomimetic natural biomaterials (BNBMs), including advances in their preparation, functionality, potential applications and future challenges. We highlight recent advances in the fabrication of BNBMs and outline general strategies for functionalizing and tailoring the BNBMs with various biological and physicochemical characteristics of native ECM. Moreover, we offer an overview of recent key advances in the functionalization and applications of versatile BNBMs for TE applications. Finally, we conclude by offering our perspective on open challenges and future developments in this rapidly-evolving field.

Advances in modified hyaluronic acid-based hydrogels for skin wound healing.

Hyaluronic acid (HA) is a natural linear anionic polysaccharide with many unique characteristics such as excellent biocompatibility and biodegradability, native biofunctionality, hydrophilicity, and non-immunoreactivity. HA plays crucial roles in numerous biological processes, including the inflammatory response, cell adhesion, migration, proliferation, differentiation, angiogenesis, and tissue regeneration. All these properties and biological functions of HA make it an appealing material for the synthesis of biomedical hydrogels for skin wound healing. Since HA is not able to be gelate alone, it must be processed and functionalized through chemical modifications and crosslinking to generate versatile HA-based hydrogels. In recent years, different physical and chemical crosslinking strategies for HA-based hydrogels have been developed and designed, such as radical polymerization, Schiff-base crosslinking, enzymatic crosslinking, and dynamic covalent crosslinking, and they have broad and promising applications in skin wound healing and tissue engineering. In this review, we focus on chemical modification and crosslinking strategies for HA-based hydrogels, aiming to provide an overview of the latest advances in the development of HA-based hydrogels for skin wound healing. We summarize and propose feasible measures for the application of HA-based hydrogels for skin treatment, and discuss future application trends, which may ultimately promote HA-based hydrogels as a promising biomaterial for clinical applications.

Osteogenic differentiation system based on biopolymer nanoparticles for stem cells in simulated microgravity.

An efficient long-term intracellular growth factor release system in simulated microgravity for osteogenic differentiation was prepared based on polylactic acid (PLA) and polyhydroxyalkanoate (PHA) nanoparticles (NPs) for loading of bone morphogenetic protein 2 (BMP2) and bone morphogenetic protein 7 (BMP7) (defined as sB2-PLA-NPs and sB7-PHA-NPs), respectively, associated with osteogenic differentiation of human adipose derived stem cells (hADSCs). On account of soybean lecithin (SL) as biosurfactants, sB2-PLA-NPs and sB7-PHA-NPs had a high encapsulation efficiency (>80%) of BMPs and uniform small size (<100 nm), and showed a different slow-release to provide BMP2 in early stage and BMP7 in late stages of osteogenic differentiation within 20 d, due to degradation rate of PLA and PHA in cells. After uptake into hADSCs, by comparison with single sB2-PLA-NPs or sB7-PHA-NPs, the Mixture NPs compound of sB2-PLA-NP and sB7-PHA-NP with a mass ratio of 1:1, can well-promote ALP activity, expression of OPN and upregulated related osteo-genes. Directed osteo-differentiation of mixture NPs was similar to result of sustained free-BMP2 and BMP7-supplying (sFree-B2&B7) in simulated microgravity, which demonstrated the reliability and stability of Mixture NPs as a long-term osteogenic differentiation system in space medicine and biology in future.

A Micro-Ark for Cells: Highly Open Porous Polyhydroxyalkanoate Microspheres as Injectable Scaffolds for Tissue Regeneration.

To avoid large open surgery using scaffold transplants, small-sized cell carriers are employed to repair complexly shaped tissue defects. However, most cell carriers show poor cell adherences and viability. Therefore, polyhydroxyalkanoate (PHA), a natural biopolymer, is used to prepare highly open porous microspheres (OPMs) of 300-360 µm in diameter, combining the advantages of microspheres and scaffolds to serve as injectable carriers harboring proliferating stem cells. In addition to the convenient injection to a defected tissue, and in contrast to poor performances of OPMs made of polylactides (PLA OPMs) and traditional less porous hollow microspheres (PHA HMs), PHA OPMs present suitable surface pores of 10-60 µm and interconnected passages with an average size of 8.8 µm, leading to a high in vitro cell adhesion of 93.4%, continuous proliferation for 10 d and improved differentiation of human bone marrow mesenchymal stem cells (hMSCs). PHA OPMs also support stronger osteoblast-regeneration compared with traditional PHA HMs, PLA OPMs, commercial hyaluronic acid hydrogels, and carrier-free hMSCs in an ectopic bone-formation mouse model. PHA OPMs protect cells against stresses during injection, allowing more living cells to proliferate and migrate to damaged tissues. They function like a micro-Noah's Ark to safely transport cells to a defect tissue.

Combined antibacterial and osteogenic in situ effects of a bifunctional titanium alloy with nanoscale hydroxyapatite coating.

To resolve the problems of bacterial infections and the low efficiency of osteogenesis of implanted titanium alloys in clinical dental and bone therapy, we developed a bifunctional titanium alloy (Ti) with a nano-hydroxyapatite (HA) coating (HBD + BMP/HA-Ti), which enables the sustained release of the natural antimicrobial peptide human ß-defensin 3 (HBD-3) and bone morphogenetic protein-2 (BMP-2). Due to the poriferous nano-sized structure of the HA coating with a 20-30 µm thickness, the HBD + BMP/HA-Ti material had a high encapsulation efficiency (>74%) and exhibited synchronized slow release of HBD-3 and BMP-2. In an antibacterial test, HBD + BMP/HA-Ti prevented the growth of bacteria in an inoculated medium, and its surface remained free from viable bacteria after a continuous incubation with Gram-negative and Gram-positive strains for 7 days. Furthermore, good adhesion, proliferation and osteogenic differentiation of hBMSCs in contact with HBD + BMP/HA-Ti were achieved in 7 days. Therefore, the bifunctional titanium alloy HBD + BMP/HA-Ti has a great potential for eventual applications in the protection of implants against bacteria in the orthopaedic and dental clinic.

Development of poly(vinyl alcohol) porous scaffold with high strength and well ciprofloxacin release efficiency.

Hydrophilic porous polymer scaffolds have shown great application in drug controlled release, while their mechanical properties and release efficiency still need further improvement. In the current study, the porous scaffolds of polyvinyl alcohol (PVA) prepared by quenching in liquid nitrogen and freeze drying method from different original concentration aqueous solutions were fabricated. Among different PVA scaffolds, the scaffold stemming from 18wt.% PVA aqueous solution exhibited the best mechanical properties, 10.5 and 1.54MPa tensile strengths for the dry and hydrogel states respectively. The inner morphology of such PVA scaffold was unidirectional honeycomb-like structure with average microchannel section of 0.5µm, and the scaffold showed porosity of 71% and rather low ciprofloxacin (Cip) release efficiency of 54.5%. Then poly(ethylene glycol) (PEG) was incorporated to enhance the Cip release efficiency. The release efficiency reached 89.3% after introducing 10wt.% PEG, and the mechanical properties of scaffold decreased slightly. Various characterization methods demonstrated that, adding PEG could help to enlarge the microchannel, create extra holes on the channel walls, weaken the interaction between PVA chains and Cip, and miniaturize the crystal size of Cip. All these effects benefit the dissolution and diffusion of Cip from scaffold, increasing its release capability. Moreover, based on biocompatible material composition, PVA/PEG scaffold is a non-cytotoxicity and have been verified that it can promote cell growth. And PVA/PEG scaffolds loaded with Cip can completely inhibit the growth of microorganism because of Cip sustaining release. The PVA scaffold would have a good potential application in tissue engineering, demanding high strength and well drug release capability.

Poly(3,4-ethylenedioxythiophene)/graphene oxide composite coating for electrode-tissue interface.

Owing to interacting with the living tissue directly, the electrode-tissue interface largely determines the performance of the whole bioelectronics devices. The miniaturization of biomedical electronic components requires interface materials to possess properties including excellent electrical performance, good biocompatibility and compatibility with microelectronic fabrication process. Considering the unique characteristics and wide applications in biomedical domain of conducting polymer and graphene, composite film consists of poly(3,4-ethylenedioxythiophene) (PEDOT) and graphene oxide (GO) is proposed as electrode-tissue interface in this work. The facilely electrochemically synthesized PEDOT/GO coating on microelectrodes shows low impedance, high charge storage capacity and good biocompatibility to act as electrode-tissue interface. As a result, the composite film is a potential biomaterial as electrode-tissue interface for tissue engineering and further implantable electrophysiological devices.

Graphene oxide doped conducting polymer nanocomposite film for electrode-tissue interface.

One of the most significant components for implantable bioelectronic devices is the interface between the microelectrodes and the tissue or cells for disease diagnosis or treatment. To make the devices work efficiently and safely in vivo, the electrode-tissue interface should not only be confined in micro scale, but also possesses excellent electrochemical characteristic, stability and biocompatibility. Considering the enhancement of many composite materials by combining graphene oxide (GO) for its multiple advantages, we dope graphene oxide into poly(3,4-ethylenedioxythiophene) (PEDOT) forming a composite film by electrochemical deposition for electrode site modification. As a consequence, not only the enlargement of efficient surface area, but also the development of impedance, charge storage capacity and charge injection limit contribute to the excellent electrochemical performance. Furthermore, the stability and biocompatibility are confirmed by numerously repeated usage test and cell proliferation and attachment examination, respectively. As electrode-tissue interface, this biomaterial opens a new gate for tissue engineering and implantable electrophysiological devices.