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.
Combining the advantages of microspheres and scaffolds, highly open porous microspheres (OPMs) made of polyhydroxyalkanoate (PHA) are developed as injectable carriers harboring growing stem cells. The PHA OPMs protect the stem cells from stresses during injection, allowing more living cells to proliferate and migrate to damaged tissues, functioning like a micro‐Noah's Ark to safely transport cells to a designated tissue location for regeneration.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Androgenetic alopecia (AGA), the most prevalent clinical hair loss, lacks safe and effective treatments due to downregulated angiogenic genes and insufficient vascularization in the perifollicular ...microenvironment of the bald scalp in AGA patients. In this study, a hyaluronic acid (HA) based hydrogel-formed microneedle (MN) was designed, referred to as V-R-MNs, which was simultaneously loaded with vascular endothelial growth factor (VEGF) and the novel hair loss drug Ritlecitinib, the latter is encapsulated in slowly biodegradable polyhydroxyalkanoates (PHAs) nanoparticles (R-PHA NPs) for minimally invasive AGA treatment. The integration of HA based hydrogel alongside PHA nanoparticles significantly bolstered the mechanical characteristics of microneedles and enhanced skin penetration efficiency. Due to the biosafety, mechanical strength, and controlled degradation properties of HA hydrogel formed microneedles, V-R-MNs can effectively penetrate the skin's stratum corneum, facilitating the direct delivery of VEGF and Ritlecitinib in a minimally invasive, painless and long-term sustained release manner. V-R-MNs not only promoted angiogenesis and improve the immune microenvironment around the hair follicle to promote the proliferation and development of hair follicle cells, but also the application of MNs to the skin to produce certain mechanical stimulation could also promote angiogenesis. In comparison to the clinical drug minoxidil for AGA treatment, the hair regeneration effect of V-R-MN in AGA model mice is characterized by a rapid onset of the anagen phase, improved hair quality, and greater coverage. This introduces a new, clinically safer, and more efficient strategy for AGA treatment, and serving as a reference for the treatment of other related diseases.
A hyaluronic acid (HA) based hydrogel-formed microneedle (MN) was designed, referred to as V-R-MNs, which was simultaneously loaded with vascular endothelial growth factor (VEGF) and the novel hair loss drug Ritlecitinib, the latter is encapsulated in slowly biodegradable polyhydroxyalkanoates (PHAs) nanoparticles (R-PHA NPs) for minimally invasive Androgenetic alopecia (AGA) treatment. The V-R-MNs promote angiogenesis and improve the immune microenvironment around the hair follicle, fostering the proliferation and development of hair follicle cells. In comparison to the clinical drug minoxidil for AGA treatment, V-R-MN exhibits a hair regeneration effect in AGA model mice characterized by a rapid onset of the anagen phase, improved hair quality, and greater coverage. Display omitted
•Designed a HA-hydrogel microneedles, simultaneously integrated VEGF and Ritlecitinib contained in PHA NPs for AGA treatment.•R-PHA NP addition enhances microneedle hardness, aiding minimally invasive transdermal delivery of microneedles.•V-R-MN group showed faster, superior hair regeneration than monotherapy (V-MN, R-MN, Ritlecitinib, and Minoxidil).•V-R-MN shows high biocompatibility with skin, ensuring safety and feasibility for transdermal drug delivery.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Different forms of biopolyester PHBVHHx microspheres were prepared so as to compare the mammalian cell behaviors in suspension cultivation system. Based on a microbial terpolyester PHBVHHx consisting ...of 3-hydroxybutyrate (HB), 3-hydroxyvalerate (HV), and 3-hydroxyhexanoate (HHx), solid microspheres (SMSs), hollow microspheres (HMSs), and porous microspheres (PMS) were successfully prepared by a modified solvent evaporation method involving gas-in-oil-in-water (G1/O/W2) double emulsion, water-in-oil-in-water (W1/O/W2) double emulsion and oil-in-water (O/W) single emulsion, respectively. Generally, PMSs have diameters ranging from 330 to 400 μm with pore sizes of 10 to 60 μm. The pores inside the PMSs were found well interconnected compared with PHBVHHx prepared by the traditional solvent evaporation method, resulting in the highest water uptake ratio. When inoculated with human osteoblast-like cells lasting 6 days, PMS showed much better cell attachment and proliferation compared with other less porous microspheres due to its large inner space as a 3 D carrier. Cell migration towards surface and other interconnected inner pores was clearly observable. Dead or apoptotic cells were found more common among less porous SMSs or HMSs compared with highly porous PMSs. It is therefore concluded that porous PHBVHHx microspheres with larger surface open pores and interconnected inner pores can serve as a carrier or scaffold supporting more and better cell growth for either injectable purposes or simply supporting cell growth.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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
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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.
Polyhydroxyalkanoates (PHAs), a family of natural microbial biopolyesters
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with excellent biodegradability and biosafety, can be produced optimally
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synthetic biology and designed to various medical devices for medical applications.
Bone Morphogenetic Protein 4 (BMP4) is crucial for bone and cartilage tissue regeneration, essential in medical tissue engineering, cosmetology, and aerospace. However, its cost and degradation ...susceptibility pose significant clinical challenges. To enhance its osteogenic activity while reducing dosage and administration frequency, we developed a novel long-acting BMP4 delivery system using poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) (PBVHx) nanoparticles with soybean lecithin-modified BMP4 (sBP-NPs). These nanoparticles promote directed osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) through sustained BMP4 release. sBP-NPs exhibited uniform size (100–200 nm) and surface charges, with higher BMP4 entrapment efficiency (82.63 %) compared to controls. After an initial burst release within 24 h, sBP-NPs achieved 80 % cumulative BMP4 release within 20 days, maintaining levels better than control BP-NPs with unmodified BMP4. Co-incubation and nanoparticle uptake experiments confirmed excellent biocompatibility of sBP-NPs, promoting hBMSC differentiation towards osteogenic lineage with increased expression of type I collagen, calcium deposition, and ALP activity (> 20,000 U/g protein) compared to controls. Moreover, hBMSCs treated with sBP-NPs exhibited heightened expression of osteogenic genetic markers, surpassing control groups. Hence, this innovative strategy of sustained BMP4 release from sBP-NPs holds potential to revolutionize bone regeneration in minimally invasive surgery, medical cosmetology or space environments.
To overcome the challenges of inactivation and degradation of the costly bone morphogenetic protein 4 (BMP4), extend its release duration, and maximize its clinical efficacy, we devised an innovative long-acting BMP4 release system utilizing poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) (PBVHx, or PHBVHHx) nanoparticles (BP-NPs) with few copolymer of poly(lactic-glycolic acid) coupled polyethyleneimine (PLGA-PEI).With stable release of BMP4 over 20 days, this system aims to guide the osteoinductivity of human stem cells with high calcium deposition, high alkaline phosphatase (ALP) activity, and upregulation of bone-related genetic markers. Display omitted
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Infection and rejection in musculoskeletal trauma often pose challenges for natural healing, prompting the exploration of biomimetic organ and tissue transplantation as a common alternative solution. ...Polyhydroxyalkanoates (PHAs) are a large family of biopolyesters synthesised in microorganism, demonstrating excellent biocompatibility and controllable biodegradability for tissue remodelling and drug delivery. With different monomer-combination and polymer-types, multi-mechanical properties of PHAs making them have great application prospects in medical devices with stretching, compression, twist in long time, especially in musculoskeletal tissue engineering. This review systematically summarises the applications of PHAs in multiple tissues repair and drug release, encompassing areas such as bone, cartilage, joint, skin, tendons, ligament, cardiovascular tissue, and nervous tissue. It also discusses challenges encountered in their application, including high production costs, potential cytotoxicity, and uncontrollable particle size distribution. In conclusion, PHAs offer a compelling avenue for musculoskeletal system applications, striking a balance between biocompatibility and mechanical performance. However, addressing challenges in their production and application requires further research to unleash their full potential in tackling the complexities of musculoskeletal regeneration.
Due to its rapid growth and high rate ofspread, Phyllostachys pubescens can suppress otherspecies, eventually leading to pure P. pubescensforests. Research on the patterns of litterdecomposition and ...nutrient release from P.pubescens across stand mixtures are helpful tounderstand the decomposition and nutrient dynamicsduring the invasion process. However, little is knownfor unmanaged conditions at high elevations.Therefore, we studied the decomposition of four littercompositions comprised of different combinations ofP.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Although considerable progress has been made in identifying the genes regulating accumulation of hormones that are involved in leaf senescence, only a few studies have focused on natural variations ...in jasmonates content and much less on the underlying genetic basis. Moreover, the epigenetic regulation of jasmonate-mediated leaf senescence remains largely unknown, in this study, we carried out metabolic profiling of a worldwide collection of rice accessions and demonstrated that there are substantial variations in jasmonate levels among these accessions. A subsequent metabolite-based genornewide association study identified candidates for two major quantitative genes （QTGs）, OsPME1 and OsTSD2, affecting the content of jasmonates. Further investigations using a series of relevant mutants and transgenic lines revealed the MeOH-jasmonata cascade plays an important role in regulating leaf senescence. Moreover, we showed that OsSRT1, one of the two Sir2 （silent information regugator 2） homologs in rice, negatively regulates leaf senescence by repressing expression of the biosynthetic genes of this metabolic cascade and at least particiaUy through histone H3K9 deacetylation of OsPME1. Taken together, our results indicate that the MeOH-jasmonates cascade and its epigenetic regulation are crucial for controlling leaf senescence process in rice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Heteroatoms and oxygen-vacancies synergistically tune the electronic property and Bader charge transference of the as-prepared catalyst to facilitate efficient electrochemical water-splitting.
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•Heteroatoms/oxygen-vacancy defects are used to jointly tailor electronic structure.•Mo-NiCo LDHs(Vo) exhibits outstanding oxygen/hydrogen evolution reaction activity.•Mo-NiCo LDHs(Vo) exhibits excellent long-time stability in overall water splitting.•The intrinsic activity of Mo-NiCo LDHs(Vo) is optimized by the new Mo active-site.
The development of earth-abundant and high-efficiency bifunctional electrocatalysts is extremely desirable for electrochemical water splitting, but there are some critical challenges that need to be addressed. The coordinated tailoring of electronic structure and Bader charge transference by heteroatom doping and oxygen vacancy defects are one of the strongest tactics to enhance the oxygen and hydrogen evolution reactions (OER and HER) of catalysts. Herein, a novel Mo-decorated nickel–cobalt layered double hydroxides 3D honeycomb nanoflake on Ni foam (labeled as Mo-NiCo LDHs(Vo)) as bifunctional electrode materials with enriched oxygen vacancy defects, excellent geometric stability, and enriched active sites was successfully fabricated through a facile hydrothermal reaction strategy. Density functional theory computations and experimental results confirmed that the electrocatalytic intrinsic activity of Mo-NiCo LDHs(Vo) was optimized not only because of the provision of new active sites by the Mo dopants via the construction of defects and oxygen vacancies but also because of the activation of the local electronic structures of the surrounding Ni and Co sites. Consequently, Mo-NiCo LDHs(Vo) exhibited outstanding electrocatalytic performance with an overpotential of 258 mV for OER and 194 mV for HER at a current density of 10 mA/cm2 in an alkaline medium. In addition, the catalyst exhibited excellent long-term stability after 100 h of use as a bifunctional electrode for overall water splitting. This work provides a facile means to fabricate superior, efficient noble metal-free catalysts with well-designed defects at the atomic-level using electronic structure engineering for energy-related applications.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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