An implantable blood clot–based immune niche for enhanced cancer vaccination

Fan, Qin; Ma, Qingle; Bai, Jingyu; Xu, Jialu; Fei, Ziying; Dong, Ziliang; Maruyama, Atsushi; Leong, Kam W.; Liu, Zhuang; Wang, Chao

doi:10.1126/sciadv.abb4639

Cited by 69 publications

(63 citation statements)

References 41 publications

(43 reference statements)

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“…2 j and k), suggesting a long-term sustained drug release behavior in vivo . Meanwhile, the degradation of blood clot gel in vivo was similar to the results we previously reported [ 37 ]. First, the degradation of blood clot was relatively slow in the first three days, and the subsequent degradation speed increased, and it was completely metabolized and cleared up in about 15 days ( Appendix A , Appendix A ).…”

Section: Resultssupporting

confidence: 89%

“…There are several unique and unprecedented properties of blood clots for bone defect regeneration. Firstly, the innate immune response can be effectively initiated and regulated by the blood clot locally, resulting in the recruitment of many various immune cells as we previously reported [ 37 ]; Secondary, the composition of platelets and plasma in the blood clot containing various growth factors makes blood clot benefit for the bone reparation; At last, due to the deep-red color, blood clots could be easily heated by near-infrared light (NIR) irradiation [ 38 ] to induce mild hyperthermia in the site of defect, which promotes the bone generation as well [ 38 , 39 ].…”

Section: Introductionmentioning

confidence: 99%

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Implantable blood clot loaded with BMP-2 for regulation of osteoimmunology and enhancement of bone repair

Fan

Bai

Shan

et al. 2021

Bioactive Materials

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The treatment of large-area bone defects still faces many difficulties and challenges. Here, we developed a blood clot delivery platform loaded with BMP-2 protein (BMP-2@BC) for enhanced bone regeneration. Blood clot gel platform as natural biomaterials can be engineered from autologous blood. Once implanted into the large bone defect site, it can be used for BMP-2 local delivery, as well as modulating osteoimmunology by recruiting a great number of macrophages and regulating their polarization at different stages. Moreover, due to the deep-red color of blood clot gel, mild localized hyperthermia under laser irradiation further accelerated bone repair and regeneration. We find that the immune niche within the bone defect microenvironment can be modulated in a controllable manner by the blood clots implantation and laser treatment. We further demonstrate that the newly formed bone covered almost 95% of the skull defect area by our strategy in both mice and rat disease models. Due to the great biocompatibility, photothermal potential, and osteoimmunomodulation capacity, such technology shows great promise to be used in further clinical translation.

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Section: Resultssupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Implantable blood clot loaded with BMP-2 for regulation of osteoimmunology and enhancement of bone repair

Fan

Bai

Shan

et al. 2021

Bioactive Materials

Self Cite

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“…developed an implantable natural blood clot‐mediated tumor vaccine system with good biocompatibility ( Figure A). [ 28 ] The internal network of the blood clot gel contained a large number of damaged RBCs, which attracted the accumulation of immune cells to enhance antitumor immunity. When the implanted blood clot was loaded with specific tumor‐associated antigens (TAA) and adjuvants, the recruited immune cells were stimulated to become tumor antigen‐specific immune cells, forming an effective and personalized tumor vaccine.…”

Section: Cell‐based Delivery Systemsmentioning

confidence: 99%

Cell‐Based Delivery Systems: Emerging Carriers for Immunotherapy

Wang

Ding

et al. 2021

Adv Funct Materials

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Immunotherapy is leading a paradigm shift in the treatment of various diseases, including tumors, auto‐immune diseases, and infectious diseases. However, the limited response rate and systemic side effects significantly impede the clinical applications of immunotherapy. As natural carriers for proteins and molecules, cells with low immunogenicity and toxicity have attracted considerable attention for biomedical applications and have achieved encouraging progress especially in immunotherapy. The convergence of multiple disciplines has equipped cell‐based delivery systems with control over their spatiotemporal distribution to enhance treatment efficacy and reduce side effects. Here, an overview of the fundamentals and design principles of cell‐based delivery systems followed by a perspective that includes the most recent advances of various cells as delivery carriers, with a special focus on the implications of cell‐based delivery systems for immunotherapy is offered.

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“…[76] Given their unique capabilities, GAGs have become promising biomaterials for regulating complicated binding events and scavenging various cytokines. [77] GAG hydrogels have been further developed to capture multiple cytokines and modulate the inflammatory status in chronic wounds. In one study, hydrogels constructed from multiple desulfated heparin derivatives and star-shaped poly(ethylene glycol) could effectively attenuate the chemoattractant activities of IL-8 and MCP-1 in an excisional wound model (Figure 4A).…”

Section: Hydrogel Scaffoldsmentioning

confidence: 99%

Capturing Cytokines with Advanced Materials: A Potential Strategy to Tackle COVID‐19 Cytokine Storm

et al. 2021

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as 2019-nCoV), [1] has caused more than 83 million infections and 1.8 million deaths globally as of January 1, 2021. [2] In the past 200 years, multiple epidemics induced by emerging viruses, such as SARS-CoV, Zika virus, Ebola virus, and recently SARS-CoV-2, have posed unprecedented threats to global public health. [3] Although several vaccine candidates have been approved by the U.S. Food and Drug Administration (FDA) for emergency prevention of SARS-CoV-2 infection, so far there is still absence of effective therapeutic options for patients with COVID-19. [4] Thus, it is of paramount importance to develop therapeutic approaches for COVID-19 and other potential pandemics.Similar to SARS-CoV infection, SARS-CoV-2 relies on spike proteins and angiotensin-converting enzyme 2 (ACE2) receptors for cell infection. [5][6][7] Once the virus enters human body, macrophages and monocytes secrete abundant proinflammatory cytokines, promoting pathogen elimination and tissue recovery. However, an exaggerated release of cytokines, known as a "cytokine storm" (or "cytokine release syndrome"), may worsen inflammatory status and result in immune-system-initiated organ damage. [8] Clinically, the majority of patients with COVID-19 appear asymptomatic or mildly symptomatic, while ≈20% of COVID-19 cases developThe COVID-19 pandemic, induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused great impact on the global economy and people's daily life. In the clinic, most patients with COVID-19 show none or mild symptoms, while approximately 20% of them develop severe pneumonia, multiple organ failure, or septic shock due to infection-induced cytokine release syndrome (the so-called "cytokine storm"). Neutralizing antibodies targeting inflammatory cytokines may potentially curb immunopathology caused by COVID-19; however, the complexity of cytokine interactions and the multiplicity of cytokine targets make attenuating the cytokine storm challenging. Nonspecific in vivo biodistribution and dose-limiting side effects further limit the broad application of those free antibodies. Recent advances in biomaterials and nanotechnology have offered many promising opportunities for infectious and inflammatory diseases. Here, potential mechanisms of COVID-19 cytokine storm are first discussed, and relevant therapeutic strategies and ongoing clinical trials are then reviewed. Furthermore, recent research involving emerging biomaterials for improving antibody-based and broad-spectrum cytokine neutralization is summarized. It is anticipated that this work will provide insights on the development of novel therapeutics toward efficacious management of COVID-19 cytokine storm and other inflammatory diseases.

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An implantable blood clot–based immune niche for enhanced cancer vaccination

Cited by 69 publications

References 41 publications

Implantable blood clot loaded with BMP-2 for regulation of osteoimmunology and enhancement of bone repair

Implantable blood clot loaded with BMP-2 for regulation of osteoimmunology and enhancement of bone repair

Cell‐Based Delivery Systems: Emerging Carriers for Immunotherapy

Capturing Cytokines with Advanced Materials: A Potential Strategy to Tackle COVID‐19 Cytokine Storm

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