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, SAZU, SBCE, SBMB, UL, UM, UPUK
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.
3D bioprinting technology can rapidly process cell-loaded biomaterials to prepare personalized scaffolds for repairing defective tissues, tissue regeneration, and even printing tissues or organs. 3D ...bioprinting relies on bioinks with appropriate rheology and cytocompatibility, and hydrogels are among the most promising bioink materials for 3D bioprinting. Among many hydrogel precursor materials, hyaluronic acid (HA) stands out due to its excellent physicochemical and biological properties, such as biocompatibility, hydrophilicity, non-immunogenicity, and complete biodegradability, and has become the most attractive hydrogel precursor for bioinks. In this review, we discuss the strategies adopted for the application of HA-based hydrogels as bioinks, including printability, improving their mechanical properties, and printing with loaded cells. Finally, we summarize the application of 3D bioprinted HA-based hydrogels in various tissue engineering applications in recent years, with the aim to provide fresh inspiration for further development of HA-based hydrogels for 3D bioprinting.
•Review the recent application of 3D bioprinted HA-based hydrogels in tissues engineering and prospect its future challenges.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In contrast to the early acting bone morphogenetic protein 2, bone morphogenetic protein 7 (BMP7) plays a decisive role mainly in the late stages of bone formation. To overcome deactivation and ...degradation of expensive BMP7, we designed a novel long‐acting BMP7 release system based on poly(3‐hydroxybutyrate‐co‐4‐hydroxybutyrate) (P34HB) nanoparticles to enable the induction of osteogenic differentiation in human adipose mesenchymal stem cells (ADSCs). In order to improve the encapsulation efficiency of BMP7 and avoid damage by organic solvents, BMP7 was modified and protected using the biosurfactant soybean lecithin. In an in vitro test, BMP7‐soybean lecithin‐P34HB nanoparticles (BMP7‐SPNPs) showed a short initial burst of BMP7 release during the first 24h, followed by a steady increase to a cumulative 80% release in 20days. Compared with the rapid release of control P34HB nanoparticles without soybean phospholipids loaded with BMP7 without soybean lecithin, BMP7‐SPNPs significantly reduced the initial burst of BMP7 release and stabilized the content of BMP7 to allow long‐term osteogenic differentiation during the late phase of bone development. Human ADSCs treated with BMP7‐SPNPs showed higher alkaline phosphatase activity and higher expression levels of genetic markers of osteogenic differentiation compared with the control group. Thus, the results indicate that BMP7‐SPNPs can be used as a rapid and long‐acting BMP7 delivery system for osteogenic differentiation.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Since the end of 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. The RNA genome of SARS-CoV-2, which is highly ...infectious and prone to rapid mutation, encodes both structural and nonstructural proteins. Vaccination is currently the only effective method to prevent COVID-19, and structural proteins are critical targets for vaccine development. Currently, many vaccines are in clinical trials or are already on the market. This review highlights ongoing advances in the design of prophylactic or therapeutic vaccines against COVID-19, including viral vector vaccines, DNA vaccines, RNA vaccines, live-attenuated vaccines, inactivated virus vaccines, recombinant protein vaccines and bionic nanoparticle vaccines. In addition to traditional inactivated virus vaccines, some novel vaccines based on viral vectors, nanoscience and synthetic biology also play important roles in combating COVID-19. However, many challenges persist in ongoing clinical trials.
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
Based on their excellent biocompatibility and adjustable biodegradability, the two natural polyesters polylactic acid (PLA) and polyhydroxyalkanoates (PHAs) have been widely used in medical ...engineering and regenerative medicine. Different types of natural biopolyester microspheres (NBPMs) composed of PLA, PHAs and their derivatives have been designed and used in diverse micro-devices in the last few decades, offering promise for diverse biomedical applications. In addition to biocompatibility and biodegradability, the structure and surface topology of NBPMs also affects in vitro and in vivo cell behaviors such as proliferation, metabolism and differentiation, which are often neglected. In this review, we summarized the preparation methods and properties of diverse NBPMs, including solid, hollow, open porous, and nanofibrous structures, as well as smooth, golf-ball-like, wrinkled, convex, rough and Janus surface topologies, respectively. Moreover, the advantages and limitations of NBPMs for medical applications are analyzed, including tissue engineering (e.g., regeneration of bone, cartilage, liver, tooth, myocardium, and skin), cell engineering for in vitro 3D cell culture, transportation, and cryopreservation, as well as different drug-release models. Finally, we discuss possible future applications of NBPMs with novel, more complex surface structures in light of current trends in biomedicine.
•Summarized characteristics and preparation of various natural biopolyester microspheres (NBPMs) with different structures and topology morphologies.•Reviewed applications of NBPMs in biomedical field.•Discussed the development and challenges of NBPMs for biomedical applications in the future.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Torealize intelligent and personalized medicine, it is a huge challenge to develop a hydrogel dressing that can be used as a sensor to monitor human health in real-time while promoting wound healing. ...Herein, an injectable, self-healing, and conductive chitosan-based (CPT) hydrogel with pH responsiveness and intrinsic antibacterial properties was fabricated via a Schiff base linkage and a hydrogen bond. Due to the introduction of Schiff base bonds, the injectable CPT hydrogel exhibits various excellent properties, such as pH responsiveness to sol–gel transition, self-healing properties, and broad-spectrum antibacterial properties even without additional antibacterial agents. In vitro experiments verify the excellent biocompatibility of the as-prepared hydrogel. An in vivo experiment in a mouse full-thickness skin-wound model was performed to confirm the outstanding effect on wound healing. Meanwhile, as epidermal sensors, the conductive hydrogel that perceives various human activities in real-time could provide the real-time analysis of the patient’s healthcare information. Based on these excellent properties, the CPT hydrogel, as a biological dressing with a sensing function, lays a solid foundation for the further realization of personalized medicine.
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IJS, KILJ, NUK, PNG, UL, UM
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
Differently to most chemically synthesized medical materials, polyhydroxyalkanoates (PHAs) are intracellular carbon and energy storage granules, which is a family of natural bio‐polymers synthesized ...by microorganism's materials. Due to excellent biocompatibility reasonable biodegradability and versatile material difference, PHAs are well medical biomaterials candidates for applications in tissue engineering and drug delivery, including commercial PHB, PHBV, PHBHHx, PHBVHHx, P34HB and few uncommercial PHAs. Electrospinning nanofibers with the size of 10–10,000 nm can improve the mechanical properties and decrease the crystallinity of PHA, meanwhile simulate the structure and function of native extracellular matrix of cells. Hence, PHAs electrospinning nanofibers as engineered scaffolds have been widely used for tissue engineering scaffolds in cardiovascular, vascular, nerve, bone, cartilage and skin; also, as carriers for application in drug delivery system. In this review, we highlight the extraction and properties of medical PHAs from natural or engineered microorganism, and microstructure, current manufacturing techniques and medical applications of electrospinning nanofibers of PHAs. Moreover, the current challenges and prospects of PHAs electrospinning nanofibers are discussed rationally, providing an insight into developing vibrant fields of PHAs electrospinning nanofibers‐based biomedicine.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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