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A Versatile Calcium Phosphate Nanogenerator for Tumor Microenvironment-activated Cancer Synergistic Therapy (Adv. Healthcare Mater. 23/2021)
Lian-Hua Fu,Chunying Li,Weimin Yin,Yan-Ru Hu,Tuanwei Sun,Yilin Wan,Jing Lin,Zhiming Li,Peng Huang
doi : 10.1002/adhm.202170110
Volume 10, Issue 23 2170110
Tunicate-Inspired Photoactivatable Proteinic Nanobombs for Tumor-Adhesive Multimodal Therapy (Adv. Healthcare Mater. 23/2021)
Yeonsu Jeong,Yun Kee Jo,Mou Seung Kim,Kye Il Joo,Hyung Joon Cha
doi : 10.1002/adhm.202170111
Volume 10, Issue 23 2170111
3D Liver Tissue Model with Branched Vascular Networks by Multimaterial Bioprinting (Adv. Healthcare Mater. 23/2021)
Xin Liu,Xinhuan Wang,Liming Zhang,Lulu Sun,Heran Wang,Hao Zhao,Zhengtao Zhang,Wenli Liu,Yiming Huang,Shen Ji,Jingjinqiu Zhang,Kai Li,Biaobiao Song,Chun Li,Hui Zhang,Song Li,Shu Wang,Xiongfei Zheng,Qi Gu
doi : 10.1002/adhm.202170114
Volume 10, Issue 23 2170114
Zwitterion-Driven Shape Program of Prodrug Nanoassemblies with High Stability, High Tumor Accumulation, and High Antitumor Activity (Adv. Healthcare Mater. 23/2021)
Guanting Li,Bingjun Sun,Shunzhe Zheng,Lu Xu,Wenhui Tao,Dongyang Zhao,Jiang Yu,Shuwen Fu,Xuanbo Zhang,Haotian Zhang,Yinglei Zhai,Cong Luo,Huaiwei Ding,Zhonggui He,Jin Sun
doi : 10.1002/adhm.202170115
Volume 10, Issue 23 2170115
Broad-Spectrum Antiviral Peptides and Polymers
Agnès Kuroki,Joyce Tay,Guan Huei Lee,Yi Yan Yang
doi : 10.1002/adhm.202101113
Volume 10, Issue 23 2101113
As the human cost of the pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still being witnessed worldwide, the development of broad-spectrum antiviral agents against emerging and re-emerging viruses is seen as a necessity to hamper the spread of infections. Various targets during the viral life-cycle can be considered to inhibit viral infection, from viral attachment to viral fusion or replication. Macromolecules represent a particularly attractive class of therapeutics due to their multivalency and versatility. Although several antiviral macromolecules hold great promise in clinical applications, the emergence of resistance after prolonged exposure urges the need for improved solutions. In the present article, the recent advancement in the discovery of antiviral peptides and polymers with diverse structural features and antiviral mechanisms is reviewed. Future perspectives, such as, the development of virucidal peptides/polymers and their coatings against SARS-CoV-2 infection, standardization of antiviral testing protocols, and use of artificial intelligence or machine learning as a tool to accelerate the discovery of antiviral macromolecules, are discussed.
Plasmonic Oxygen Defects in MO3?x (M = W or Mo) Nanomaterials: Synthesis, Modifications, and Biomedical Applications
Mingzhu Zhou,Yachong Liu,Yan Su,Qianqian Su
doi : 10.1002/adhm.202101331
Volume 10, Issue 23 2101331
Nanomedicine is a promising technology with many advantages and provides exciting opportunities for cancer diagnosis and therapy. During recent years, the newly developed oxygen-deficiency transition metal oxides MO3?x (M = W or Mo) have received significant attention due to the unique optical properties, such as strong localized surface plasmon resonance (LSPR) , tunable and broad near-IR absorption, high photothermal conversion efficiency, and large X-ray attenuation coefficient. This review presents an overview of recent advances in the development of MO3?x nanomaterials for biomedical applications. First, the fundamentals of the LSPR effect are introduced. Then, the preparation and modification methods of MO3?x nanomaterials are summarized. In addition, the biological effects of MO3?x nanomaterials are highlighted and their applications in the biomedical field are outlined. This includes imaging modalities, cancer treatment, and antibacterial capability. Finally, the prospects and challenges of MO3?x and MO3?x-based nanomaterial for fundamental studies and clinical applications are also discussed.
A Versatile Calcium Phosphate Nanogenerator for Tumor Microenvironment-activated Cancer Synergistic Therapy
Lian-Hua Fu,Chunying Li,Weimin Yin,Yan-Ru Hu,Tuanwei Sun,Yilin Wan,Jing Lin,Zhiming Li,Peng Huang
doi : 10.1002/adhm.202101563
Volume 10, Issue 23 2101563
Gas therapy is an emerging “green” cancer treatment strategy; however, its outcome often restricted by the complexity, diversity, and heterogeneity of tumor. Herein, a tumor targeting and tumor microenvironment-activated calcium phosphate nanotheranostic system (denoted as GCAH) is constructed for effective synergistic cancer starvation/gas therapy. GCAH is obtained by a facile biomineralization strategy using glucose oxidase (GOx) as a biotemplate, followed by loading of l-Arginine (L-Arg) and modification of hyaluronic acid (HA) to allow special selectivity for glycoprotien CD44 overexpressed cancer cells. This nanotheranostic system not only exhausts the glucose nutrients in tumor region by the GOx-triggered glucose oxidation, the generated H2O2 can oxidize L-Arg into NO under acidic tumor microenvironment for enhanced gas therapy. As such, there are significant enhancement effects of starvation therapy and gas therapy through the cascade reactions of GOx and L-Arg, which yields a remarkable synergistic therapeutic effect for 4T1 tumor-bearing mice without discernible toxic side effects.
Tunicate-Inspired Photoactivatable Proteinic Nanobombs for Tumor-Adhesive Multimodal Therapy
Yeonsu Jeong,Yun Kee Jo,Mou Seung Kim,Kye Il Joo,Hyung Joon Cha
doi : 10.1002/adhm.202101212
Volume 10, Issue 23 2101212
Near-IR (NIR) light-responsive multimodal nanotherapeutics have been proposed to achieve improved therapeutic efficacy and high specificity in cancer therapy. However, their clinical application is still elusive due to poor biometabolization and short retention at the target site. Here, innovative photoactivatable vanadium-doped adhesive proteinic nanoparticles (NPs) capable of allowing biological photoabsorption and NIR-responsive anticancer therapeutic effects to realize trimodal photothermal-gas-chemo-therapy treatments in a highly biocompatible, site-specific manner are proposed. The photoactivatable tumor-adhesive proteinic NPs can enable efficient photothermal conversion via tunicate-inspired catechol–vanadium complexes as well as prolonged tumor retention by virtue of mussel protein-driven distinctive adhesiveness. The incorporation of a thermo-sensitive nitric oxide donor and doxorubicin into the photoactivatable adhesive proteinic NPs leads to synergistic anticancer therapeutic effects as a result of photothermal-triggered “bomb-like” multimodal actions. Thus, this protein-based phototherapeutic tumor-adhesive NPs have great potential as a spatiotemporally controllable therapeutic system to accomplish effective therapeutic implications for the complete ablation of cancer.
3D Liver Tissue Model with Branched Vascular Networks by Multimaterial Bioprinting
Lian-Hua Fu,Chunying Li,Weimin Yin,Yan-Ru Hu,Tuanwei Sun,Yilin Wan,Jing Lin,Zhiming Li,Peng Huang
doi : 10.1002/adhm.202101405
Volume 10, Issue 23 2101405
Complicated vessels pervade almost all body tissues and influence the pathophysiology of the human body significantly. However, current fabrication strategies have limited success at multiscale vascular biofabrication. This study reports a methodology to fabricate soft vascularized tissue at centimeter scale using multimaterial bioprinting by a customized multistage-temperature-control printer. The printed constructs can be perfused via the branched endothelialized vasculatures to support the well-formed 3D capillary networks, which ensure cellular activities with sufficient nutrient supply and then mimic a mature and functional liver tissue in terms of synthesis of liver-specific proteins. Moreover, an inner and external pressure-bearing layer is printed to support the direct surgical anastomosis of the carotid artery to the jugular vein. In summary, a versatile platform to recapitulate the vasculature network is presented, in which case sustaining the optimal cellularization in engineered tissues is achievable.
Zwitterion-Driven Shape Program of Prodrug Nanoassemblies with High Stability, High Tumor Accumulation, and High Antitumor Activity
Guanting Li,Bingjun Sun,Shunzhe Zheng,Lu Xu,Wenhui Tao,Dongyang Zhao,Jiang Yu,Shuwen Fu,Xuanbo Zhang,Haotian Zhang,Yinglei Zhai,Cong Luo,Huaiwei Ding,Zhonggui He,Jin Sun
doi : 10.1002/adhm.202101407
Volume 10, Issue 23 2101407
Prodrug nanoassemblies have emerged as a promising platform for the delivery of anticancer drugs. PEGylation is a “gold standard” to improve colloidal stability and pharmacokinetics of nanomedicines. However, the clinical application of PEG materials is challenged by in vivo oxidative degradation and immunogenicity. Rational design of advanced biomaterials for the surface modification of nanomedicines is the hot spot of research. Here, a zwitterionic sulfobetaine surfactant is constructed as a novel surface modifier to coassemble with 10-hydroxycamptothecin-linoleic acid conjugate, with the classical PEGylated material as control. Interestingly, both the type and ratio of surfactants have profound impacts on the molecular mechanisms of the assembly of prodrugs, thereby affecting the pharmaceutical properties. Compared with PEGylated spherical prodrug nanoassemblies, zwitterion-modified prodrug nanoassemblies have distinct rod shape and superhydrophilic surface, and exhibit potent antitumor activity due to the combination of multiple advantages in terms of colloidal stability, cellular uptake, and pharmacokinetics. The findings illustrate the crucial role of zwitterionic surfactants as the surface modifier in the determination of in vivo fate of the prodrug nanoassemblies, and pave the way for the development of advanced nanomedicines.
Tunable 3D Hydrogel Microchannel Networks to Study Confined Mammalian Cell Migration (Adv. Healthcare Mater. 23/2021)
Katharina Siemsen,Sunil Rajput,Florian Rasch,Fereydoon Taheri,Rainer Adelung,Jan Lammerding,Christine Selhuber-Unkel
doi : 10.1002/adhm.202170113
Volume 10, Issue 23 2170113
Tunable 3D Hydrogel Microchannel Networks to Study Confined Mammalian Cell Migration
Katharina Siemsen,Sunil Rajput,Florian Rasch,Fereydoon Taheri,Rainer Adelung,Jan Lammerding,Christine Selhuber-Unkel
doi : 10.1002/adhm.202100625
Volume 10, Issue 23 2100625
Cells adapt and move due to chemical, physical, and mechanical cues from their microenvironment. It is therefore important to create materials that mimic human tissue physiology by surface chemistry, architecture, and dimensionality to control cells in biomedical settings. The impact of the environmental architecture is particularly relevant in the context of cancer cell metastasis, where cells migrate through small constrictions in their microenvironment to invade surrounding tissues. Here, a synthetic hydrogel scaffold with an interconnected, random, 3D microchannel network is presented that is functionalized with collagen to promote cell adhesion. It is shown that cancer cells can invade such scaffolds within days, and both the microarchitecture and stiffness of the hydrogel modulate cell invasion and nuclear dynamics of the cells. Specifically, it is found that cell migration through the microchannels is a function of hydrogel stiffness. In addition to this, it is shown that the hydrogel stiffness and confinement, influence the occurrence of nuclear envelope ruptures of cells. The tunable hydrogel microarchitecture and stiffness thus provide a novel tool to investigate cancer cell invasion as a function of the 3D microenvironment. Furthermore, the material provides a promising strategy to control cell positioning, migration, and cellular function in biological applications, such as tissue engineering.
Self-Healing of Hyaluronic Acid to Improve In Vivo Retention and Function
Anna Gilpin,Yuze Zeng,Jiaul Hoque,Ji Hyun Ryu,Yong Yang,Stefan Zauscher,William Eward,Shyni Varghese
doi : 10.1002/adhm.202100777
Volume 10, Issue 23 2100777
Convergent advances in the field of soft matter, macromolecular chemistry, and engineering have led to the development of biomaterials that possess autonomous, adaptive, and self-healing characteristics similar to living systems. These rationally designed biomaterials can surpass the capabilities of their parent material. Herein, the modification of hyaluronic acid (HA) to exhibit self-healing properties is described, and its physical and biological function both in vitro and in vivo is studied. The in vitro findings showed that self-healing HA designed to undergo self-repair improves lubrication, enhances free radical scavenging, and attenuates enzymatic degradation compared to unmodified HA. Longitudinal imaging following intraarticular injection of self-healing HA shows improved in vivo retention despite its low molecular weight. Concomitant with these functions, intraarticular injection of self-healing HA mitigates anterior cruciate ligament injury-mediated cartilage degeneration in rodents. This proof-of-concept study shows how incorporation of functional properties such as self-healing can be used to surpass the existing capabilities of biolubricants.
A Prevascularized Polyurethane-Reinforced Fibrin Patch Improves Regenerative Remodeling in a Rat Right Ventricle Replacement Model
Ze-Wei Tao,Dillon K. Jarrell,Andrew Robinson,Elizabeth M. Cosgriff-Hernandez,Jeffrey G. Jacot
doi : 10.1002/adhm.202101018
Volume 10, Issue 23 2101018
Congenital heart defects (CHDs) affect 1 in 120 newborns in the United States. Surgical repair of structural heart defects often leads to arrhythmia and increased risk of heart failure. The laboratory has previously developed an acellular fibrin patch reinforced with a biodegradable poly(ether ester urethane) urea mesh that result in improved heart function when tested in a rat right ventricle wall replacement model compared to fixed pericardium. However, this patch does not drive significant neotissue formation. The patch materials are modified here and this patch is prevascularized with human umbilical vein endothelial cells and c-Kit+ human amniotic fluid stem cells. Rudimentary capillary-like networks form in the fibrin after culture of cell-encapsulated patches for 3 d in vitro. Prevascularized patches and noncell loaded patch controls are implanted onto full-thickness heart wall defects created in the right ventricle of athymic nude rats. Two months after surgery, defect repair with prevascularized patches results in improved heart function and the patched heart area exhibited greater vascularization and muscularization, less fibrosis, and increased M2 macrophage infiltration compared to acellular patches.
3D-Printed Reinforcement Scaffolds with Targeted Biodegradation Properties for the Tissue Engineering of Articular Cartilage
Enrico Tosoratti,Philipp Fisch,Scott Taylor,Lee Ann Laurent-Applegate,Marcy Zenobi-Wong
doi : 10.1002/adhm.202101094
Volume 10, Issue 23 2101094
Achieving regeneration of articular cartilage is challenging due to the low healing capacity of the tissue. Appropriate selection of cell source, hydrogel, and scaffold materials are critical to obtain good integration and long-term stability of implants in native tissues. Specifically, biomechanical stability and in vivo integration can be improved if the rate of degradation of the scaffold material matches the stiffening of the sample by extracellular matrix secretion of the encapsulated cells. To this end, a novel 3D-printed lactide copolymer is presented as a reinforcement scaffold for an enzymatically crosslinked hyaluronic acid hydrogel. In this system, the biodegradable properties of the reinforced scaffold are matched to the matrix deposition of articular chondrocytes embedded in the hydrogel. The lactide reinforcement provides stability to the soft hydrogel in the early stages, allowing the composite to be directly implanted in vivo with no need for a preculture period. Compared to pure cellular hydrogels, maturation and matrix secretion remain unaffected by the reinforced scaffold. Furthermore, excellent biocompatibility and production of glycosaminoglycans and collagens are observed at all timepoints. Finally, in vivo subcutaneous implantation in nude mice shows cartilage-like tissue maturation, indicating the possibility for the use of these composite materials in one-step surgical procedures.
Dual Extrusion Patterning Drives Tissue Development Aesthetics and Shape Retention in 3D Printed Nipple-Areola Constructs
Sarah Van Belleghem,Bhushan Mahadik,Kirstie Snodderly,Zoe Mote,Bin Jiang,Justine R. Yu,Shannon McLoughlin,Xiaoming He,Arthur J. Nam,John P. Fisher
doi : 10.1002/adhm.202101249
Volume 10, Issue 23 2101249
Breast cancer and its most radical treatment, the mastectomy, significantly impose both physical transformations and emotional pain in thousands of women across the globe. Restoring the natural appearance of a nipple-areola complex directly on the reconstructed breast represents an important psychological healing experience for these women and remains an unresolved clinical challenge, as current restorative techniques render a flattened disfigured skin tab within a single year. To provide a long-term solution for nipple reconstruction, this work presents 3D printed hybrid scaffolds composed of complementary biodegradable gelatin methacrylate and synthetic non-degradable poly(ethylene) glycol hydrogels to foster the regeneration of a viable nipple-areola complex. In vitro results showcased the robust structural capacity and long-term shape retention of the nipple projection amidst internal fibroblastic contraction, while in vivo subcutaneous implantation of the 3D printed nipple-areola demonstrated minimal fibrotic encapsulation, neovascularization, and the formation of healthy granulation tissue. Envisioned as subdermal implants, these nipple-areola bioprinted regenerative grafts have the potential to transform the appearance of the newly reconstructed breast, reduce subsequent surgical intervention, and revolutionize breast reconstruction practices.
Facet-Dependent Biodegradable Mn3O4 Nanoparticles for Ameliorating Parkinson's Disease
Zhuojia Xu,Aihua Qu,Weiwei Wang,Meiru Lu,Baimei Shi,Chen Chen,Changlong Hao,Liguang Xu,Maozhong Sun,Chuanlai Xu,Hua Kuang
doi : 10.1002/adhm.202101316
Volume 10, Issue 23 2101316
Parkinson's disease (PD) is a common neurodegeneration disease. Unfortunately, there are no effective measures to prevent or inhibit this disease. In this study, biodegradable Mn3O4 nanoparticles (NPs) in different shapes are prepared and enclosed them by {100}, {200} and {103} facets that exhibit facet-dependent protection against neurotoxicity induced by oxidative damage in a cell model of PD. Notably, Mn3O4 nanorods enclosed by {103} facets exhibit high levels of enzyme-like activity to eliminate reactive oxygen specie in vitro. It is also determined that the uptake pathway of Mn3O4 NPs into MN9D cells is mediated by caveolin. The data demonstrate that Mn3O4 nanorods can be taken up by cells effectively and confer excellent levels of neuroprotection while the biodegradation of Mn3O4 NPs in vivo is confirmed by photoacoustic image of Mn3O4 NPs in brain at 60 d. Furthermore, the oxygen scavenging effect created by Mn3O4 nanorods is successfully applied to a mouse model of PD; the amount of ?-synuclein in the cerebrospinal fluid of PD mice is reduced by 61.2% in two weeks, thus demonstrating the potential application of facet-directed Mn3O4 NPs for the clinical therapy of neurodegenerative disease.
?-Catenin Limits Osteogenesis on Regenerative Materials in a Stiffness-Dependent Manner
Qi Zhou,Xiaoyan Ren,Michelle K. Oberoi,Meiwand Bedar,Rachel M. Caprini,Marley J. Dewey,Vasiliki Kolliopoulos,Dean T. Yamaguchi,Brendan A. C. Harley,Justine C. Lee
doi : 10.1002/adhm.202101467
Volume 10, Issue 23 2101467
Targeted refinement of regenerative materials requires mechanistic understanding of cell–material interactions. The nanoparticulate mineralized collagen glycosaminoglycan (MC-GAG) scaffold is shown to promote skull regeneration in vivo without additive exogenous growth factors or progenitor cells, suggesting potential for clinical translation. This work evaluates modulation of MC-GAG stiffness on canonical Wnt (cWnt) signaling. Primary human bone marrow-derived mesenchymal stem cells (hMSCs) are differentiated on two MC-GAG scaffolds (noncrosslinked, NX-MC, 0.3 kPa vs conventionally crosslinked, MC, 3.9 kPa). hMSCs increase expression of activated ?-catenin, the major cWnt intracellular mediator, and the mechanosensitive YAP protein with near complete subcellular colocalization on stiffer MC scaffolds. Overall Wnt pathway inhibition reduces activated ?-catenin and osteogenic differentiation, while elevating BMP4 and phosphorylated Smad1/5 (p-Smad1/5) expression on MC, but not NX-MC. Unlike Wnt pathway downregulation, isolated canonical Wnt inhibition with ?-catenin knockdown increases osteogenic differentiation and mineralization specifically on the stiffer MC. ?-catenin knockdown also increases p-Smad1/5, Runx2, and BMP4 expression only on the stiffer MC material. Thus, while stiffness-induced activation of the Wnt and mechanotransduction pathways promotes osteogenesis on MC-GAG, activated ?-catenin is a limiting agent and may serve as a useful target or readout for optimal modulation of stiffness in skeletal regenerative materials.
Polydopamine Nanosheets Doped Injectable Hydrogel with Nitric Oxide Release and Photothermal Effects for Bacterial Ablation and Wound Healing
Genhua Liu,Lu Wang,Ye He,Liucan Wang,Zhiwen Deng,Junjie Liu,Dan Peng,Tao Ding,Lu Lu,Yao Ding,Jixi Zhang,Peng Liu,Kaiyong Cai
doi : 10.1002/adhm.202101476
Volume 10, Issue 23 2101476
The development of wound dressings with combined antibacterial activities and pro-healing functions has always been an intractable medical task for treating bacterial wound infection. Herein, a novel injectable hybrid hydrogel dressing is developed, which is doped with nitric oxide (NO) donor (N,N’-di-sec-butyl-N,N’-dinitroso-1,4-phenylenediamine, BNN6) loaded two-dimensional polydopamine nanosheets (PDA NS). The hydrogel matrix is in situ formed through dynamic Schiff base crosslinking between hydrazide-modified ?-polyglutamic acid (?-PGA-ADH) and aldehyde-terminated Pluronic F127 (F127-CHO). Under 808 nm irradiation, the embedded PDA NS exhibits outstanding photothermal transform properties (56.1%) and on-demand NO release. The combination of photothermal and NO gas therapy with a synergistic antibacterial effect works on both Escherichia coli and Staphylococcus aureus in vitro. Furthermore, a full-thickness skin defect model also demonstrates that the hybrid hydrogel shows outstanding antibacterial properties and effectively accelerates the wound healing process. Overall, this study provides a facile and promising method for the fabrication of PDA NS based multifunctional hydrogel dressing for the application of infectious skin wound healing.
Development of Nickel Selenide@polydopamine Nanocomposites for Magnetic Resonance Imaging Guided NIR-II Photothermal Therapy
Wenxue Hu,Wenyao Zhen,Mengchao Zhang,Wei Wang,Xiaodan Jia,Shangjie An,Yue Wang,Zhuo Guo,Xiue Jiang
doi : 10.1002/adhm.202101542
Volume 10, Issue 23 2101542
The penetration depth of near-infrared laser has greatly restricted the development of most photothermal agents. Recently, photothermal agents in the second near-infrared (NIR-II) window have drawn great attention as they can overcome above barrier. Herein, a novel “all in one” NIR-II responsive nanoplatform (nickel selenide @polydopamine nanocomposites, NiSe@PDA NCs) based on in situ coating the polydopamine (PDA) on the surface of biomineralized nickel selenide nanoparticles (NiSe NPs) for dual-model imaging-guided photothermal therapy is reported. Under the illumination of NIR-II laser (1064 nm), the photothermal conversion efficiency of NiSe@PDA NCs can reach 48.4%, which is higher than that of single NiSe NPs due to the enhanced molar extinction coefficient. In addition, because of the paramagnetic effect of NiSe NPs, the constructed NiSe@PDA NCs can be acted as T1 contrast agent for magnetic resonance imaging (MRI). Most importantly, the MRI contrast effect is enhanced with the coating of PDA layer due to the loose structure of PDA. Ultimately, both in vitro and in vivo experiments demonstrate that the developed NCs can achieve efficient MRI-guided photothermal therapy for treating malignant tumor. Therefore, the designed NiSe@PDA NCs with excellent features show great potential for clinical MRI-guided cancer therapy.
Bioinspired Artificial Liver System with hiPSC-Derived Hepatocytes for Acute Liver Failure Treatment
Jinglin Wang,Haozhen Ren,Yuxiao Liu,Lingyu Sun,Zhuohao Zhang,Yuanjin Zhao,Xiaolei Shi
doi : 10.1002/adhm.202101580
Volume 10, Issue 23 2101580
Bioartificial liver (BAL) system has become a promising alternative to traditional liver transplantation in rescuing acute liver failure (ALF) patients. Herein, inspired by natural microstructure of hepatic lobules, a novel biomimetic bioartificial liver system (BBALS) is developed by integrating human induced pluripotent stem cell-derived hepatocytes (hiPSC-Heps) -laden microparticles and semipermeable microtubes into a microfluidic platform. As the working units are hepatic lobules-like semipermeable microtubes surrounding with serum-free suspension differentiated hiPSC-Heps microcarriers, the BBALS is endowed with functional cell aggregates and effective circulation system. Thus, the BBALS possesses high cell viability, favorable function regeneration, and effective substances exchange. Based on these features, a 3D liver chip with multiple parallel BBALS units is created for filtering the plasma of ALF rabbits, which validates the research significance and application potential of the proposed BBALS. Moreover, the novel integrated BBALS is applied to treat ALF rabbits and shows great advantages in increasing survival, generating serum proteins, and decreasing inflammation. These properties point to the broad prospects of BBALS in treating related diseases and improving traditional clinical methods.
Unraveling an Innate Mechanism of Pathological Mineralization-Regulated Inflammation by a Nanobiomimetic System
Dongyang Wang,Xiaomeng Wang,Lei Huang,Ziyi Pan,Kexuan Liu,Beibei Du,Ying Xue,Bei Li,Yuan Zhang,Huan Wang,Daowei Li,Hongchen Sun
doi : 10.1002/adhm.202101586
Volume 10, Issue 23 2101586
Pathological mineralization (PTM) often occurs under inflammation and affects the prognosis of diseases, such as atherosclerosis and cancers. However, how the PTM impacts inflammation has not been well explored. Herein, poly lactic-co-glycolic acid (PLGA)/gelatin/hydroxyapatite (HA) electrospun nanofibers are rationally designed as an ideal PTM microenvironment biomimetic system for unraveling the role of PTM on inflammation. The results demonstrate that the inflammatory response decreases continuously during the process of mineralization. When mature macromineralization forms, the inflammation almost completely disappears. Mechanistically, the PTM formation is mediated by matrix proteins, local high calcium, and cell debris (nuclei), or actively regulated by the lysosomal/plasma membrane components secreted by macrophages. These inflammatory inducible factors (calcium, cell debris, etc.) can be “buried” through PTM process, resulting in reduced immune responses. Overall, the present study demonstrates that PTM is an innate mechanism of inflammation subsidence, providing valuable insight into understanding the action of mineralization on inflammation.
Bioinspired Redwood-Like Scaffolds Coordinated by In Situ-Generated Silica-Containing Hybrid Nanocoatings Promote Angiogenesis and Osteogenesis both In Vitro and In Vivo
Minhao Wu,Feixiang Chen,Ping Wu,Zhiqiang Yang,Sheng Zhang,Lingfei Xiao,Zhouming Deng,Chong Zhang,Yun Chen,Lin Cai
doi : 10.1002/adhm.202101591
Volume 10, Issue 23 2101591
Inspired by natural redwood and bone, a biomimetic strategy is presented to develop a highly bioactive redwood-like nanocomposite via radial freeze casting of biocompatible hydrogels followed by the in situ coprecipitation of a Si-containing CaP hybrid nanocoating (SCPN). The engineered material displays radially aligned macrochannels and a porous network structure similar to those of natural redwood. In addition to acting as a mechanical reinforcement, introducing SCPNs into the weak redwood-like scaffold yields not only a nanoroughened surface topography, a low swelling ratio, retarded enzymatic degradation, and enhanced protein absorption abilities but also the sustained sequential release of Si and Ca ions, thereby providing essential biophysical and biochemical cues for effective bone regeneration. Benefiting from the redwood-like structures and bioactive SCPNs, the biomimetic materials create a favorable microenvironment for promoting the initial adhesion, spreading, proliferation, and migration of bone marrow-derived mesenchymal stem cells and human umbilical vein endothelial cells. Furthermore, the in vitro and in vivo data showed that the biocompatible redwood-like scaffold with precipitated SCPN can synergistically promote osteogenesis and angiogenesis in their aligned direction. Collectively, this work presents a novel bioinspired redwood-like material with multifunctional properties that provides new insight into bone defect repair.
Construction of pH-Dependent Nanozymes with Oxygen Vacancies as the High-Efficient Reactive Oxygen Species Scavenger for Oral-Administrated Anti-Inflammatory Therapy
Ning Zhao,Fei-Er Yang,Cong-Ying Zhao,Shi-Wen Lv,Jin Wang,Jing-Min Liu,Shuo Wang
doi : 10.1002/adhm.202101618
Volume 10, Issue 23 2101618
It is of great significance to eliminate excessive reactive oxygen species (ROS) for treating inflammatory bowel disease (IBD). Herein, for the first time, a novel nanozyme NiCo2O4@PVP is constructed via a step-by-step strategy. Noticeably, the existence of oxygen vacancy in the NiCo2O4@PVP is helpful for capturing oxygenated compounds, while both redox couples of Co3+/Co2+ and Ni3+/Ni2+ will offer richer catalytic sites. As expected, the obtained NiCo2O4@PVP exhibits pH-dependent multiple mimic enzymatic activities. Benefiting from the introduction of polyvinylpyrrolidone (PVP), the NiCo2O4@PVP possesses good physiological stability and excellent biosafety in stomach and intestines’ environment. Meanwhile, the NiCo2O4@PVP also presents strong scavenging activities to ROS in vitro, including •O2?, H2O2, as well as •OH. Furthermore, a dextran sodium sulfate (DSS)-induced colitis model is established for evaluating the anti-inflammatory activity of NiCo2O4@PVP in vivo. Based on the size-mediated and charge-mediated mechanisms, the nanozyme can pass through the digestive tract and target the inflamed site for oral-administrated anti-inflammatory therapy. More interestingly, compared with the model group, the expression levels of inflammatory factors (e.g., Interleukin- 6 (IL-6), Interleukin- 1? (IL-1?), tumor necrosis factor-? (TNF-?), and inducible nitric oxide synthase (iNOS)) in colon of mice show a significant decrease after nanozyme intervention, thereby inhibiting the development of IBD. In short, current work provides an alternative therapy for patients suffering from IBD.
Microbubble Functionalization with Platelet Membrane Enables Targeting and Early Detection of Sepsis-Induced Acute Kidney Injury
Jing Yang,Xiaoyan Miao,Yu Guan,Chaojin Chen,Sufang Chen,Xinmin Zhang,Xue Xiao,Zheng Zhang,Zhengyuan Xia,Tinghui Yin,Ziqing Hei,Weifeng Yao
doi : 10.1002/adhm.202101628
Volume 10, Issue 23 2101628
The morbidity and mortality of sepsis-induced acute kidney injury (SAKI) remain high. Early detection using molecular ultrasound imaging may reduce mortality and improve the prognosis. Inspired by the intrinsic relationship between platelets and SAKI, platelet membrane-coated hybrid microbubbles (Pla-MBs) are designed for early recognition of SAKI. Pla-MBs are prepared by ultrasound-assisted recombination of liposomes and platelets, consisting of inherent platelet membrane isolated from platelets. By coating with platelet membranes, Pla-MBs are endowed with various adhesive receptors (such as integrin ?IIb?3), providing a benefit for selective adhesion to damaged endothelium in SAKI. In a rat SAKI model, by combining the advantages of molecular ultrasound imaging and platelet membrane, Pla-MBs display platelet-mimicking properties and achieve the early targeted diagnosis of SAKI prior to the regular laboratory markers of kidney function. Moreover, the expression of platelet-binding proteins (von Willebrand factor and fibrinogen) in the kidneys shows consistent results with molecular ultrasound imaging. Together, microbubble functionalization with platelet membranes is diagnostically beneficial for SAKI and might be a promising modality for endothelial injury diseases in the future.
