50 results about "Cell recruitment" patented technology

Aiming at the challenge of osteochondral defect repair, the invention provides a preparation method of a fiber-reinforced self-repairing hydrogel scaffold (SBPS). According to the method, phenylboronic acid modified sodium alginate, polyvinyl alcohol and fibroin nanofibers rich in beta-Sheet are utilized to form the hydrogel through dynamic boric acid ester bonds and hydrogen bonds. The SBPS hydrogel loaded with PDGF-BB is combined with the nanosheet containing LDH / ChS / TGF-beta3, so that multi-dimensional synergy of mechanical strengthening, sequential drug release (PDGF-BB is released in an early stage and TGF-beta3 / Mg < 2 + > is released in a later stage), ROS removal and endogenous repair is realized. The Mg < 2 + > concentration gradient effect further assists staged regulation (vascularized bone regeneration-cartilage matrix synthesis), and breaks through the limitation of a single factor. Experiments prove that the scaffold can effectively drive angiogenesis, stem cell recruitment and cartilage / bone differentiation in vivo and in vitro, and finally osteochondral regeneration with structure-function matching is achieved.

The invention relates to application of a cGAS-STING signal channel inhibitor in preparation of a product for preventing or treating abdominal adhesion, and belongs to the technical field of biological medicines. The invention finds that peritoneal dialysis causes that a peritoneal mesothelial cell cGAS-STING pathway and downstream protein thereof are activated, inflammatory factors are generated, and the peritoneal mesothelial cell secretes a chemotactic factor CCL2 (MCP-1) participating in macrophage recruitment, so that migration of macrophages can be promoted, and abdominal adhesion is caused. The cGAS-STING signaling pathway inhibitor can be used for relieving the effects, so that the aim of treating abdominal adhesion is fulfilled.

The present disclosure provides anticancer agents containing a multispecific antigen-binding molecule that can efficiently and specifically recruit T cells to the target cancer cells, particularly CLDN6-expressing cancer cells and such, and can treat cancer through the cytotoxic activity of T cells against target cancer tissues containing CLDN6-expressing cells; combination therapies using the anticancer agent and at least one other anticancer agent; and pharmaceutical compositions for use in the combination therapies.

Lymphedema is characterized by the accumulation of protein-rich interstitial fluid, lipids and a significant inflammatory cell infiltrate in the limb. It causes a significant morbidity and is a common disabling disease affecting more than 250 million people worldwide, however there is no curative treatment for lymphedema. Here, the inventors found that dermolipectomies from patient with lymphedema exhibit inflamed gene expression profile compared to normal arm on same patient. After lipidomic analysis, the inventors identified severe decrease in arachidonic acid-derived lipid mediators generated by the 15-lipoxygenase (15-LOX) in lymphedematous arms. Using a mouse model of lymphedema, they reproduced the etiology of the human pathology including the loss of specialized pro-resolving lipid mediators that play essential roles in resolution of inflammation. This was associated with a lack of regulatory T cells (Treg) recruitment in the injured limb adipose tissue. Importantly, the inventors identified the lymphatic endothelial 15-LOX was responsible for the chemoattraction and transendothelial migration of Tregs. These results were confirmed by an aggravation of lymphedema and deterioration of the lymphatic network in an original transgenic mouse model in which ALOX15 gene is selectively deleted in the lymphatic system. Importantly, this was reversed by the injection of 15-LOX expressing lentivectors. These results provide evidence that lymphatic lipoxygenase may represent a novel therapeutic target for lymphedema by serving as a mediator of Treg invasion into lymphedematous adipose tissue.

The invention provides in-situ forming fluid bionic hydrogel as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The invention provides an injectable GelSSO / PDA (at) SDF fluid bionic niche, after in-situ photo-crosslinking, preferential and sustained release of PDA (at) SDF NPs initiates early signal amplification, which recruits EPCs and MSCs through an SDF-1 alpha / CXCR4 axis, promotes activation of the angiogenic vascular niche through an AKT signal, and repolarizes macrophages to a regenerated M2 phenotype. Subsequently, the gradual degradation of the bionic niche triggers the stable release of SSO, and the later signal is further amplified to form an osteogenic niche with transcriptional activity, thereby maintaining the MAPK / ERK-mediated MSCs osteogenic differentiation. The fluid bionic niche can form a niche conforming to defects through photopolymerization, the local immune imbalance and endogenous progenitor cell recruitment are corrected in the early stage, then formation of new vessels and lamellar bones is promoted, and finally vascularization regeneration of diabetic skull defects is achieved.

The invention belongs to the field of biomedical materials and tissue engineering, and particularly relates to an injectable mineralized collagen bone repair composite material loaded with stem cell recruitment factors and osteogenic induction factors and a preparation method of the injectable mineralized collagen bone repair composite material. The composite material is composed of 50%-53% of mineralized collagen matrix particles, 15%-20% of SDF-1alpha loaded heparinized gelatin microspheres, 15%-20% of BMP-2 loaded PDA coated mesoporous silica particles, 8%-10% of an NHS-PEG-NHS cross-linking agent and 4%-6% of glycerin. The composite material can realize time-space sequential regulation and control of'collection first and then differentiation '; a bionic bone matrix microenvironment is provided through the mineralized collagen matrix; the problems of two-factor release conflict and stability are solved; in-vitro experiments show that the material can significantly promote stem cell migration and osteogenic differentiation, and animal experiments prove that the material can recover 82-88% of mechanical properties of bone defect parts. The invention solves the technical problems of insufficient stem cell collection, low osteogenic differentiation efficiency and uncontrollable factor release of the existing bone repair material.

This invention discloses a composite microsphere loaded with ZIF-8 nanoparticles and stem cell extracellular vesicles, its preparation method, and its applications. The composite microsphere comprises a hydrogel matrix microsphere, and ZIF-8 nanoparticles and small extracellular vesicles derived from bone marrow mesenchymal stem cells uniformly dispersed and encapsulated within the hydrogel matrix microsphere. This invention integrates ZIF-8 nanoparticles and stem cell-derived sEVs into injectable, photocurable GelMA microspheres, constructing an integrated delivery platform capable of sequential release and multi-stage synergistic effects. This platform successfully integrates and leverages three major functions: immunomodulation, stem cell recruitment, and cartilage-induced differentiation, ultimately achieving high-quality functional healing of the tendon-bone interface at both histological and biomechanical levels, providing a highly promising new strategy for the regeneration and repair of interfacial tissues in the musculoskeletal system.

The invention discloses a preparation method of composite microspheres for regulating and controlling a local inflammation microenvironment and promoting nerve regeneration. The method comprises the following steps: preparing liposome loaded with ginsenoside Rg1; preparing a GM microsphere loaded with a stromal cell-derived factor 1 alpha (SDF1 alpha); and preparing the inflammation regulation nerve regeneration promoting composite microspheres. The composite microsphere can reduce inflammatory response, reduce scar tissue formation, promote angiogenesis, continuously release SDF1 alpha and promote endogenous stem cell recruitment and neural differentiation. Therefore, the composite microsphere is a functional biological scaffold for firstly regulating and controlling local microenvironment inflammation of spinal cord injury and then promoting collection and differentiation of endogenous stem cells for innovative sequential inflammation regulation and nerve regeneration, and a new strategy is provided for treating spinal cord injury by tissue engineering.

To provide a composition and a method for modulating an immune system in a subject.SOLUTION: A composition and a method provide means for treating and / or preventing a disease associated with deficiency and / or dysregulation of a T-cell. The composition can include: a porous scaffold, a growth factor which is present at approximately 1ng to approximately 1000ng per scaffold, and an effective amount for inducing formation of a tissue or an organ in the scaffold and mobilizing cells into the scaffold; and a differentiation factor which induces differentiation of mobilized cells into a T-cell precursor cell.SELECTED DRAWING: None

The inventors have prepared a novel anti-Cath-D antibody (F1M1) that can reduce tumor growth in a Cath-D secreting basal-like TNBC cell line with strong immune infiltration, without significant toxicity. The F1M1 antibody prevents recruitment of immunosuppressive M2 polarized tumor-associated macrophages (TAMs) and induces activation of natural killer cells in the tumor, and the F1M1 also enhances activation of antitumor M1 polarized TAM, recruitment and maturation of conventional cDC1 dendritic cells in the tumor to promote antigen presentation and reduce depletion marker expression of CD4 + and CD8 + T cells in the tumor and drainage lymph nodes. It is worthy of noting that the affinity of the antibody F1M1 to Cath-D is better than that of the antibody F1 prepared by the inventor in advance. The inventors also have prepared a novel Fc-optimized F1M1-Fc + human antibody which can promote ADCC induction of cancer cells and CAF, improve anti-tumor efficacy, and trigger recruitment, activation and cytotoxic activity of NK cells in tumors. The F1M1-Fc + F1M1-Fc + can inhibit the growth of MDA-MB-231 and SUM159 TNBC cell xenografts and two TNBC-PDX (one of the TNBC-PDX is resistant to neoadjuvant chemotherapy), and has no obvious toxicity. In addition, the F1M1-Fc < + > improves the treatment effect of the paclitaxel and enzalutamide combined medicine. Thus, the present invention relates to anti-cathepsin-D antibodies and their use in the treatment of cancer, in particular triple negative breast cancer.

The invention belongs to the field of biological pharmacy, and relates to an anti-tumor nano-drug, in particular to a tumor-targeted anti-tumor nano-drug HPCR as well as a preparation method and application thereof. An immune checkpoint inhibitor anti-PD-L1, a chemotactic factor CCL5 and rutin with an ACE2 activation effect are respectively grafted to HA through a chemical synthesis method to synthesize HA-anti-PD-L1, HA-CCL5 and HA-RT, then the HA-anti-PD-L1, HA-CCL5 and HA-RT are synthesized into the anti-tumor nano-drug HPCR through a film hydration method, and in-vivo experiments prove that the drug has an excellent anti-tumor effect; the medicine has good T cell activation effect, T cell recruitment effect, tumor matrix elimination, T cell infiltration increase and medicine permeation effects, and provides a new method and a new thought for tumor treatment.

The present disclosure relates to an implantable vascular graft material, including: a substrate including a graft material, the substrate defining a top surface and a bottom surface; and one or more bispecific binding partners having a luminal binding domain bound to the top surface and one or more cellular binding domains. In embodiments, the disclosure includes an implantable vascular graft including: a tubular base layer including a graft material, the tubular base layer defining a luminal surface and an abluminal surface; and a fusion peptide having a heparin binding domain bound to the luminal surface and one or more monocyte binding domains. In embodiments, the present disclosure provides one or more implantable vascular grafts such as A-TEVs, methods of making vascular grafts, methods of use, and the like.

The application discloses a kind of bionic bone / cartilage double-layer composite scaffold material and its preparation method and application.The bionic bone / cartilage double-layer composite scaffold material of the application is composed of upper cartilage repair hydrogel layer and lower bone repair scaffold layer.The main feature of the application is that by radial freezing, the chitosan-chitin whisker liquid crystal composite hydrogel micron radial channel with diameter gradient change is constructed in the lower scaffold, which can promote the transport of nutrients, cell recruitment, migration and adhesion;At the same time, the drug-loaded liquid crystal hydrogel constructed in the longitudinal large channel of the scaffold and the upper cartilage repair layer can realize the sustained release of active drugs, so as to further regulate stem cell osteogenesis / cartilage differentiation and promote the generation of blood vessels, and is expected to have good application prospect as biomedical materials such as bone / cartilage tissue repair materials.

The application belongs to the field of biomedical engineering, and discloses a human live mucosa organoid and a construction method and application thereof. The construction of the organoid comprises the following steps: preparing a cell gel compound, filling the cell gel compound into a support, implanting the support into a nude mouse subcutaneously after gelation, and obtaining the human live mucosa organoid after culturing for 1-3 weeks. The application also discloses the application of the organoid in disease research or drug screening. The application constructs a sustainable in-vivo biomimetic air-mucosa gas-liquid interface, realizes the transition of mucosa from an "ex-vivo static model" to an "in-vivo dynamic live system", and realizes the comprehensive evaluation of the curative effect of anti-infection drugs from three dimensions of pathogenic bacteria elimination, inflammation reaction regulation and immune cell recruitment inhibition in application, thereby breaking through the limitation of traditional models that can only evaluate the in-vitro bacteriostatic activity and being more consistent with the actual effect of clinical drug treatment.

The invention belongs to the field of biological medicine, and discloses a novel target of ID1 protein in tumor-associated macrophages (TAM) as an anti-tumor therapeutic drug and application of the novel target. The invention discloses that the expression of ID1 in TAM is obviously higher than that of para-carcinoma tissue macrophages for the first time, and the ID1 has a tumor promoting effect. Specifically, ID1 highly expressed in TAM can enhance the dryness of tumor cells and promote tumor growth and metastasis by obstructing CD8 + T cell recruitment in tumors. The tumor promoting phenotype of the TAM can be inhibited by reducing the expression of ID1 in the TAM through gene editing. The sensitivity of tumor cells including colon cancer, liver cancer and pancreatic cancer to chemotherapeutic drugs and immune checkpoint inhibitors can be improved by reducing the expression of ID1 in TAM by using a small molecule compound. The invention discloses a new tumor regulation and control promoting signal in a tumor immune microenvironment TAM, and the ID1 protein in the provided TAM can be used as a new tumor treatment target for anti-tumor drug screening. The method lays a theoretical foundation for an anti-tumor research and development strategy, and has a huge potential conversion application prospect.

The invention discloses a space-time responsive multifunctional 3D printing bone repair scaffold as well as a preparation method and application thereof. PDGF-BB is loaded on a quick-release carrier, MgP is loaded on a slow-release carrier, and the multifunctional 3D printing bone repair scaffold with MgP loaded on the inner layer and PDGF-BB loaded on the outer layer is prepared through 3D printing. Wherein the PDGF-BB is used as an immunomodulator, the MgP is used as a regeneration inducer, and after the carrier is implanted into a body, according to different carrier degradation rates, the PDGF-BB is degraded and released in a space-time responsive manner to realize early immunoregulation and endothelial cell recruitment, and then magnesium ions and phosphate ions are degraded and released to synergistically promote vascularization and osteogenesis in middle and later periods with the PDGF-BB. In-vitro and in-vivo experiments prove that the 3D printing bone repair scaffold provided by the invention has immunoregulation, angiogenesis promotion and osteogenesis properties, can be used for repairing inflammatory bone injury, and is particularly suitable for repairing inflammatory bone injury caused by diabetes.

The invention discloses a platelet vesicle-decellularized cancellous bone composite scaffold as well as a preparation method and an application method thereof. The platelet vesicle-acellular cancellous bone composite scaffold is formed by crosslinking platelet vesicles with fibrinogen gel as a scaffold background and cancellous bone extracellular matrix particles. The preparation method of the composite scaffold comprises the following steps: firstly, separating cancellous bone blocks from bone tissues of animals, and then carrying out decellularization and demineralization treatment to obtain the cancellous bone extracellular matrix particles. Then extracting platelets, preparing vesicles through membrane extrusion, and resuspending the vesicles in normal saline containing fibrinogen; finally, under the action of thrombin or calcium ions, cross-linking the platelet vesicle and the acellular cancellous bone to form the platelet vesicle-acellular cancellous bone composite scaffold. According to the composite scaffold, platelet vesicle fibrinogen hydrogel serves as a substrate, rapid cell recruitment and vascularization of a tissue repair part are achieved, osteogenic differentiation of a specific part is completed through a decellularized cancellous bone matrix, and a new thought and new work are provided for the field of bone regeneration.

One aspect provides a biodegradable polymer scaffold for kidney regeneration comprising basic ceramic particles, an extracellular matrix, zinc particles, a material for inducing kidney regeneration, and a biodegradable polymer. The biodegradable polymer scaffold for kidney regeneration according to one aspect comprises a material for inducing kidney regeneration and / or extracellular vesicles that secrete a stem cell recruitment inducing factor, thereby guiding stem cells to a tissue damage site and enhancing kidney regeneration ability so as to effectively induce regeneration of kidney tissue. Accordingly, the biodegradable polymer scaffold can contribute to the medical device industry including the biomedical implant market.

A drug carrier, a preparation method therefor, and use thereof. The carrier is obtained by subjecting a biodegradable polymer microsphere with a chambered structure to a freeze-thaw treatment, resulting in the formation of openings or pores on the surface of the polymer microsphere, thereby enabling a gentle drug loading process. The prepared drug carrier can be used as a vaccine adjuvant, and is capable of promoting immune cell recruitment and activation, improving antibody levels and quality, inducing efficient cellular immunity, and thus improving the vaccine protection rate.

T cell recruitment molecules are provided that bind to antigens on non-immune cells and antigens on immune cells. The T cell recruitment molecules can bind to STEAP2 on cancer cells and, for example, CD3 on T cells. The T cell recruitment molecules can also bind to STEAP2 on cancer cells and, for example, CD8 on T cells. Alternatively, the T cell recruitment molecules can bind to STEAP2 on cancer cells, as well as both CD3 and CD8 on T cells.

The present invention relates to a pair of recombinant binding proteins and its uses, e.g. for activation of a effector domains upon binding to a target cell, wherein the activated effector domains are suitable of targeting T cells as well as NK cells to the target site. Specifically, the invention relates to the pair of recombinant binding proteins and pharmaceutical compositions comprising said pair of recombinant binding proteins.

The application discloses a three-layer time sequence regulation type inflammation targeting composite repair system for repairing endometrial injury and a preparation method and application thereof. The system is a three-layer composite structure, which comprises, from outside to inside, (1) an outer ROS response hydrogel layer loaded with anti-inflammatory drugs, which can respond to early high expression of active oxygen to rapidly degrade the drugs, so that acute inflammation is inhibited; (2) a middle layer of targeted delivery and metabolic repair, which is a M1 macrophage membrane pseudo-loaded drug liposome (NMN@M-Lipo), which is exposed after the degradation of the outer hydrogel, actively targets the inflammation lesion through the M1 membrane, and slowly releases nicotinamide mononucleotide (NMN) to restore cell energy metabolism; and (3) an inner layer of cell recruitment and regeneration, which is a decellularized matrix scaffold loaded with SDF-1 alpha, which continuously releases SDF-1 alpha to recruit endogenous stem cells in the later repair stage, and promotes functional regeneration of the endometrium. The application utilizes the time sequence microenvironment changes of endometrial repair, and realizes the cascade regulation of 'anti-inflammation first, metabolic repair second, and regeneration promotion third'. Animal experiments show that the system can significantly restore the reproductive function of the injured endometrium and improve the number of offspring.

The invention provides methods for genetically engineering T cells in vivo comprising administering to the subject a cytokine or nucleic acid molecule encoding a cytokine to recruit the subject's T cells to the administration site; followed by administration of a nucleic acid molecule encoding an antigen receptor. In some instances, the method also includes administering an integrase or nucleic acid molecule encoding an integrase to integrate the sequence encoding the antigen receptor into the DNA of the recruited T cells.

The invention provides a preparation method of collagen-based microspheres and application of the collagen-based microspheres in preparation of a subcutaneous tissue filling material, and relates to the technical field of medical treatment and medical cosmetology. According to verification of a large number of experiments, the collagen-based microspheres are prepared through a two-step cross-linking method and adjustment of polarity of a solvent used in the second-step chemical cross-linking process; the mass swelling ratio and the effective crosslinking density of the collagen-based microspheres can be regulated and controlled; different from a traditional filling material which only depends on physical support, the collagen-based microspheres with specific mass swelling ratio and crosslinking density have good injectability and mechanical support performance and can realize subcutaneous cell recruitment and promote cell proliferation and extracellular matrix secretion, so that a long-acting and stable subcutaneous tissue filling effect is realized. In addition, the collagen-based microspheres have good biocompatibility and degradability, and conform to the idea of cell-free tissue engineering.

T cell recruiting polypeptides are provided that bind CD3 on a T cell. The polypeptides can be used in methods for treatment of cancers.

The disclosure provides in one aspect compounds, and compositions comprising such compounds, that can be used to treat, ameliorate, and / or prevent cancer, especially colorectal cancer (CRC). In certain embodiments, the compounds of the disclosure inhibit HSP70. In other embodiments, the compounds of the disclosure promote or increase immune cell recruitment to a cancer. In yet other embodiments, the compounds of the disclosure promote and / or increase immune cell infiltration in a cancer.

The invention discloses Mxene / Zn nano coating modified CF / PEEK as well as a preparation method and application thereof. The preparation method comprises the following steps: S1, pretreating a CF / PEEK stent; s2, sulfonating the surface of the CF / PEEK stent; s3, a PEI-TA adhesive layer is constructed; s4, a CF / PEEK-MXene material is prepared; and S5, preparing the CF / PEEK-MXene coated Zn material. Through the synergistic effect of promoting osteogenesis and angiogenesis, the MXene / Zn nano-coating modified CF / PEEK stent can effectively solve the problem of mismatch of multiple biological interfaces of mechanical support-nutrition transport-cell recruitment in large-section bearing bone defect repair. The gradient mechanical adaptation characteristic of the stent can provide stable mechanical support, meanwhile, good mechanical matching with surrounding bone tissues is achieved, and the stress shielding effect is avoided. And the blood vessel-osteogenesis coupling activity ensures that the collection of cells, the transportation of nutrition and the formation of new bones can be orderly carried out in the bone repair process, so that the success rate of large-section bearing bone defect repair is greatly improved.

T cell recruiting polypeptides are provided that bind CD3 on a T cell. The polypeptides can be used in methods for treatment of cancers.

The invention provides a preparation method of gelatin-based microspheres and an application of the gelatin-based microspheres in preparation of a subcutaneous tissue filling material, and relates to the technical field of medical treatment and medical cosmetology, the inventor finds through a large number of experimental exploration verifications that the physical properties of the gelatin-based microspheres can be regulated and controlled by adjusting the polarity strength of a solvent used in a chemical crosslinking process; different from a traditional filling material only depending on physical support, gelatin-based microspheres with specific swelling ratio and crosslinking density can promote cell recruitment, proliferation and extracellular matrix secretion subcutaneously, so that long-acting and stable subcutaneous tissue filling is realized, the treatment effect can be optimized by adjusting components, and the cell-free tissue engineering concept is met. In conclusion, the gelatin-based microspheres with the specific swelling ratio, crosslinking density and components have the potential obviously superior to that of existing products in the fields of aging resistance, wound repair, postoperative tissue filling and the like, and the gelatin-based microspheres have the basis of becoming a new generation of high-performance subcutaneous tissue filling materials.

To provide T cell recruiting polypeptides binding CD3 on a T cell, which can be used in methods for treating cancers.SOLUTION: Provided is a polypeptide comprising a first and a second immunoglobulin single variable domain (ISV), the first ISV having high affinity for / binding to cluster of differentiation 3 (CD3) present on a T cell, the second ISV having high affinity for / binding to a first antigen on a target cell, the first antigen being different from the CD3, and the target cell being different from the T cell.SELECTED DRAWING: None