36 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 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 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 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 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.

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

An aspect provides a biodegradable polymer scaffold for kidney regeneration, including basic ceramic particles, an extracellular matrix, zinc particles, a kidney regeneration-inducing material, and a biodegradable polymer. A biodegradable polymer scaffold for kidney regeneration, according to an aspect, includes a kidney regeneration-inducing material and / or extracellular vesicles that secrete a stem cell recruitment-inducing factor, thereby inducing stem cells to a damaged tissue site and enhancing kidney regenerative capacity, and thus can effectively induce the regeneration of kidney tissue. Therefore, the biodegradable polymer scaffold can contribute to the medical device industry, including the bioimplant market.

The invention relates to hepatic fibrosis intervention, and provides a pharmaceutical composition for treating and / or preventing hepatic fibrosis related to TET2 function deficiency type myeloid cells and application of the pharmaceutical composition. The composition comprises: (a) an inhibitor or antagonist for inhibiting chemotactic signals mediated by CCL2 and / or CCL8 and CCR2 and / or CCR3; and (b) an IL-6 pathway inhibitor. Preferably, (a) is Bindarit or a pharmaceutically acceptable salt thereof, and (b) is an IL-6 neutralizing antibody or an IL-6 receptor antibody. According to the composition, by reducing mononuclear cell recruitment / proinflammatory mononuclear cell source macrophage infiltration and blocking IL-6 mediated hepatic stellate cell activation, collagen deposition is relieved, and fibrosis indexes such as alpha-SMA and Col1a1 are reduced. Animal experiments show that in a CCl4-induced myeloid Tet2 deletion mouse model and an old-age chimeric model, combined administration is superior to single administration.

The invention relates to COnditional Bispecific Redirected Activation constructs, or COBRAs, that are administered in an active pro-drug format. Upon exposure to tumor proteases, the constructs are cleaved and activated, such that they can bind both tumor target antigens (TTAs) as well as CD3, thus recruiting T cells expressing CD3 to the tumor, resulting in treatment.

The invention relates to an artemisia apiacea-containing penetration enhancing composition with skin cell repairing and relieving effects, and a preparation method and application thereof, and belongs to the technical field of cosmetics. The research finds that the anti-inflammatory effect generated by only inhibiting an upstream anti-inflammatory path of an NF-kappa B channel is limited, and the anti-inflammatory effect can be remarkably enhanced by blocking a downstream conduction chain while inhibiting the NF-kappa B channel. On the basis, through the artemisia apiacea extract and the flos magnoliae extract, an upstream anti-inflammatory path is inhibited, recruitment and infiltration of inflammatory cells are reduced, a downstream conduction chain is blocked, and the anti-inflammatory effect is synergistically improved. Besides, through cooperation of the oat kernel oil, the jasmine flower oil and the squalane, on one hand, the solubility of fat-soluble active matter is improved, on the other hand, the composition can participate in repairing, stabilizing and optimizing the lipid structure of the skin cuticle, synchronously open the skin fat-soluble channel and convey the active matter more efficiently, and therefore the excellent relieving, repairing and stabilizing effects are achieved.

The present invention relates to a conditionally bispecific redirected activation construct or COBRA administered in the form of an active prodrug. Upon exposure to a tumor protease, the constructs are cleaved and activated such that they are able to bind both tumor target antigens (TTAs) and CD3, thereby recruiting CD3-expressing T cells to the tumor for treatment. In some embodiments, the tumor target antigen is B7H3.

The invention belongs to the field of biomedical materials and tissue engineering, and particularly relates to a porous microsphere for filling alveolar fossa and a preparation method of the porous microsphere. The preparation method comprises the following steps: (1) modifying sodium alginate polypeptide; (2) preparing a sodium alginate-rich phase solution and a casein-rich sodium phase solution; (3) preparing sodium alginate / sodium caseinate composite microspheres by electrostatic spraying; (4) removing a sodium caseinate phase; and (5) in-situ mineralization. The microsphere prepared by the invention has injectability, a micron-sized pore structure penetrating capability, a cell collection capability and an osseointegration capability, and can effectively promote repair and regeneration of alveolar bone defects.

The invention discloses a self-adjuvant gel and an application of the self-adjuvant gel in tumor immunotherapy. According to the gel, N-acetylcysteine (NAC) is grafted with chitosan to form a sulfydryl-containing functional carrier, and the activity of T cells is effectively maintained by utilizing the interaction between NAC and sulfydryl on the surfaces of the T cells; meanwhile, the oxidized beta-glucan has Toll-like receptor 4 activation capability, and can promote the maturation and activation of dendritic cells. The formation of the gel depends on a Schiff base reaction between an aldehyde group in the oxidized beta-glucan and an amino group of the chitosan, and self-assembly gel formation under a mild condition is realized. The system can load a chemotactic factor CXCL9 and a tumor antigen at the same time, efficient recruitment of T cells is achieved by continuously releasing the CXCL9, and the antigen is synchronously and slowly released to induce specific immune response. The self-adjuvant gel has the functions of immune cell recruitment, antigen delivery and immune activation, and provides a novel material platform and strategy for tumor immunotherapy.

To provide: T cell recruiting polypeptides that bind CD3 on a T cell; and methods for treatment of cancers using the polypeptides.SOLUTION: A polypeptide comprises a first and a second immunoglobulin single variable domain (ISV). The first ISV has high affinity for / binds to cluster of differentiation 3 (CD3) present on a T cell, and the second ISV has high affinity for / binds to a first antigen on a target cell. Here, the first antigen is different from the CD3, and the target cell is different from the T cell.SELECTED DRAWING: None

The invention belongs to the technical field of pharmacy, and discloses application of sennoside A in preparation of a medicine for treating fungal keratitis. The invention proposes that sennoside A has a treatment effect on fungal keratitis for the first time. A fungal keratitis model is established by adopting a C57BL / 6 mouse, the influence of sennoside A on corneal clinical score, neutrophil recruitment, macrophage recruitment and interleukin 1 beta expression of the model mouse is researched, the influence of sennoside A on a Caspase-1 / GSDMD signal channel is verified, and meanwhile, the influence of sennoside A on neutrophil activity and macrophage polarization is verified.