152 results about "Vascularizes" patented technology

The invention provides a pourable tumor organoid vascularization model and a construction method thereof, and relates to the technical field of organoid culture. A temperature-sensitive degradable material and a photo-crosslinking modified temperature-sensitive material are used, the composite stent is printed through two channels, a multi-component gel mask partition curing process is combined, the stability of a perfusion pipeline is improved, and a partitioned highly-bionic complex microenvironment is accurately constructed in a macroscopic three-dimensional space; and constructing to obtain the perfusion tumor organ vascularization model. The model is high in bionic degree and stable in structure, can be applied to deepening cell and microenvironment interaction research and tumor-related drug screening, and has a good application prospect.

The invention relates to the technical field of tumor biomedical engineering and organ chips, in particular to a vascularized gastric cancer organ chip and a preparation method thereof.The chip is composed of an integrated micro-fluidic main body, an annular micro-column array and an optical sealing film, and a central culture cavity is divided into a tumor area and a blood vessel area by micro-columns; the preparation method comprises the following steps: injecting a fibrous protein solution containing human umbilical vein endothelial cells and cancer-related fibroblasts into a vascular region, and adding thrombin for in-situ gelation to form a pre-vascularized network; the method comprises the following steps: mixing a patient-derived gastric cancer organ with a methacrylic acid esterified gelatin pre-polymerized solution, injecting the mixture into a tumor area, and carrying out photo-crosslinking immobilization; culturing for 7-14 days under the dynamic perfusion condition of a mixed culture medium to obtain a three-dimensional gastric cancer organ model containing a capillary network; the method is expected to be used for rapid, low-cost and high-throughput screening of chemotherapy or anti-angiogenesis drugs and accurate prediction of individual curative effects of patients.

The invention discloses a bionic heterogeneous composite structure bone implant and a preparation method thereof, and relates to the technical field of medical implants.The bionic heterogeneous composite structure bone implant comprises an inner-layer cross-shaped structure, a middle-layer negative Poisson's ratio structure and an outer-layer honeycomb structure, and the cross-shaped structure, the negative Poisson's ratio structure and the honeycomb structure jointly form a bionic composite structure; and immersing the bionic composite structure subjected to double-network crosslinking into a drug-containing solution for post-treatment and drug loading to obtain the bionic heterogeneous composite structure. According to the invention, bionic adaptation and intelligent optimization of mechanical properties are realized, and the stress shielding problem is solved; according to the invention, osseointegration and vascularization processes are obviously accelerated and enhanced, and leap-type improvement of biological activity is realized; a novel intelligent treatment mode based on in-vivo microenvironment response is developed, and on-demand and accurate drug delivery is achieved.

Devices, systems, and methods for causing retrograde oxygenated blood flow in at least a portion of the venous system of the myocardium are disclosed. Devices and methods include a method for causing retrograde oxygenated blood flow in at least a portion of the venous system of the myocardium, the method comprising: implanting a variable occluder in a coronary sinus region proximate a left atrium, wherein the variable occluder is configured to gradually increase a level of blood flow restriction over a period of days to enable a venous system of the myocardium to compensate for increased pressure caused by the gradual increase in the level of blood flow restriction; and following venous system compensation, shunting oxygenated blood flow into the coronary sinus to cause retrograde flow of oxygenated blood in at least a portion of the venous system of the myocardium to thereby enable revascularization of the myocardium.

Disclosed in the present invention are a biomimetic vascularized iPSC-hep spheroid for liver regeneration, and a preparation method therefor. The biomimetic vascularized iPSC-hep spheroid is a microcapsule with a porous hyaluronic acid methacryloyl as a shell and a human-induced pluripotent stem-cell-derived hepatocyte spheroid as an inner phase, and human umbilical vein endothelial cells adhere to the surface of the shell. The biomimetic vascularized iPSC-hep spheroid of the present invention promotes effective communication between hiPSC-heps and HUVECs, and provides barrier protection for an encapsulated hiPSC-hep spheroid so as to avoid attack by the immune system. Compared with dispersed cells, the cell-to-cell interaction in the cell spheroid improves cell-to-cell communication, helps to simulate the physiological heterogeneous structure and cell microenvironment of the liver, and can more effectively repair an acutely failing liver.

The invention belongs to the field of biomedical materials and manufacturing thereof, and discloses a composite 3D printing stent with a time sequence regulation blood vessel and bone tissue regeneration function as well as a preparation method and application of the composite 3D printing stent. The method comprises the following steps: respectively loading an osteogenesis inducer and a vascular induced differentiation agent into two carrier materials with different degradation rates, and carrying out 3D printing and gel coating modification according to a reverse sequence of a physiological repair process of carrying out vascularization first and then carrying out osteogenesis to form a composite 3D printing stent of which the inner layer is loaded with the osteogenesis inducer and the outer layer is loaded with the vascular induced differentiation agent. After the composite 3D printing stent is implanted into a body, according to different degradation rates of the composite material, the repair and regeneration process of vascularization and osteogenesis is realized in a manner of degrading the gel coating and degrading the 3D printing stent, and the composite 3D printing stent has good living compatibility, biological activity and mechanical properties, and has good application prospects. The material can be used as a biomedical material for repairing or treating bone defects or self-repairing, and has a good application prospect in treatment and self-repairing of bone defects.

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 discloses a titanium-magnesium hollow screw system capable of promoting fracture healing and a manufacturing method. The titanium-magnesium hollow screw system comprises a titanium-based supporting structure and a magnesium filling layer. The titanium-based supporting structure comprises a main body part, the surface of the main body part is provided with an imitated bone trabecula part, and a plurality of bone gaps are formed in the imitated bone trabecula part; wherein bone gaps are filled with the magnesium filling layer, and the magnesium filling layer is combined with the titanium-based supporting structure in a physical embedding mode; the titanium-based supporting structure bears and maintains initial fixation and long-term bearing, so that the strength and the stability of the screw are ensured; the surface imitated bone trabecula and the communicated bone gaps increase the surface area and provide a physical channel for vascularization and bone tissue ingrowth, so that synostosis is promoted; the magnesium filling layer releases magnesium ions after being locally controllably degraded, so that osteogenesis and angiogenesis are favorably stimulated, the local biological environment is improved, instant mechanical support after an operation is ensured, bone healing is promoted through local biological activity release and structural orientation, the healing time is favorably shortened, and the healing quality is favorably improved.

The invention relates to the technical field of bone tissue engineering and regenerative medicine, and discloses a stem cell-loaded bionic bone scaffold material, which comprises a bone scaffold main body, the bone scaffold main body is formed by compounding hydroxyapatite and a biodegradable high-molecular polymer and has a porous structure, the porosity is 70%-90%, the aperture range is 100-500 microns, and pores are communicated with one another; a vascularization induction factor slow release system is arranged in the porous structure of the bone scaffold main body, the stem cell-loaded bionic bone scaffold material does not need to take the autologous bone of a patient, and the problems of donor injury and limited sources are avoided; the composite scaffold is matched with low-immunogenicity stem cells, so that the risks of immunological rejection and disease transmission are avoided; the material has the advantages of good biocompatibility, mechanical matching with human bones, degradability, no secondary operation, promotion of vascular regeneration and stem cell osteogenesis, and realization of bone regeneration integration.

The invention discloses an infectious bone defect bionic repair hydrogel stent and a preparation method and application thereof, and is characterized in that the infectious bone defect bionic repair hydrogel stent is composed of an upper antibacterial-vascularization layer simulating a periosteum structure, a middle support layer simulating a bone cortex structure and a lower regeneration-regulation layer simulating a cancellous bone structure; the upper antibacterial-vascularization layer is prepared from photoresponse CuxO / SiC heterojunction powder, the middle support layer is prepared from silk fibroin, and the lower regeneration-regulation layer is prepared from HAP (at) Cur-CNDs-Pt NPs composite nanoparticles. The multi-dimensional structure and function integration realizes the full-period regulation and control of antibiosis-barrier-regeneration, breaks through the limitation of the traditional single-function stent, and provides an integrated solution for infectious bone defect repair.

The present application relates to a kind of nasal ala base subperiosteal implant retention method, belong to plastic surgery medical instrument technical field.The present application provides a kind of nasal ala base subperiosteal implant soft tissue suspension retention method and its implant and system.The method includes: implant is placed into maxillary bone subperiosteal interstice, and implant fixed wing is fixed with the soft tissue anchor point such as alar base ligament of alar elevating lip muscle using drug-loaded degradable suture and is suspended and fixed.Implant surface is provided with the microporous structure of guiding tissue ingrowth, and is provided with the drug depot recess of filling load immunomodulator temperature-sensitive hydrogel.Postoperative healing process, suture is released under the action of tension to accelerate proangiogenic factor and promote local vascularization, and temperature-sensitive hydrogel slow-release immunomodulator induces macrophage to repair type polarization, and cooperatively promotes the biological chimeric fixation of implant and soft tissue.The present application can realize the double stable retention of implant, reduces postoperative displacement risk.

The disclosure relates to compositions useful for ligament and tendon repair and methods of preparing the same. The disclosure is particularly suitable for repair of ligament ruptures, for example, anterior cruciate ligament ruptures. In an aspect of the invention, the compositions comprise a biocompatible clay, a polymer, a polypeptide, a calcium-based mineral that form a scaffold, as well as a bioabsorbable reinforcement structure incorporated thereon and / or therein. Methods of use and manufacture of the compositions, as well as kits including the compositions, are also provided.

The application provides a alginate-based aerogel, a preparation method and application thereof. The alginate-based aerogel has parallelly arranged large pores and oriented channels at an angle with the large pores, and the angle ranges from 0 to 180 degrees. The large pores are distributed in the same direction inside the alginate-based aerogel, and the oriented channels improve the interconnectivity between the large pores. The existence of the large pores and the oriented channels makes the alginate-based aerogel have the characteristics of anisotropy and a multi-scale pore structure, and the size of the large pores and the oriented channels is suitable for inducing vascularization and osteogenesis. Therefore, the aerogel can be used as a bone scaffold material. Tests show that the aerogel has the characteristics of light weight and high strength. In addition, other components beneficial to osteogenesis can be added in the alginate system, and the size of the pores can be adjusted without affecting the formation of the pore structure.

The present application relates to a kind of pluripotent stem cell co-differentiation method for generating vascularized heart organoids, the method comprises: (1) in iPSCs, obtain iEC-iPSCs by transferring exogenous gene Tet 3G and ETV2;(2) the iEC-iPSCs in step (1) are mixed with iPSCs, add culture medium I, prepare blastula after culture;(3) the blastula in step (2) is induced by using the heart organoid differentiation method combined with doxycycline, and vascularized heart organoids are prepared after differentiation culture.The present application uses Tet-on 3G inducible expression system, promotes the differentiation of part of cells in heart organoids to endothelial cell lineage by regulating the expression of ETV2 gene in part of iPSCs in blastula, and then forms vascularized heart organoids.

The present invention relates to systems, compositions and methods for multicellular bioprinting vascularized tissue constructs comprising a hierarchical vascular network. The methods employ a dual bio-ink strategy involving fibrous microgel matrix bio-inks with adjustable hardness, self-healing rheology, and microporosity to support capillary self-assembly, and sacrificial bio-inks that define a large pourable channel after removal. The system integrates top-down printing and bottom-up cell self-organization within a programmable bio-printing platform. The key aspect of the invention is to engineer the physical topography of the matrix to actively guide vascular morphogenesis beyond conventional permissive stents. The integrated platform enables the manufacture of complex bionic vascular networks with enhanced mass delivery, cellular viability, and in vivo integration potential. The invention represents an important progress in the aspect of extendable production of functional human tissues, and has application in regenerative medicine, disease modeling and drug discovery.

The invention belongs to the technical field of biomedical engineering and microfluidics, and particularly discloses a double-channel vascularization organ chip which comprises a channel layer and a bottom layer which are arranged in a stacked mode, and the lower surface of the channel layer and the bottom layer are sealed through bonding; a culture solution channel is arranged on the lower surface of the runner layer, snakelike pipelines are symmetrically arranged on the culture solution channel, and a first liquid injection channel and a second liquid injection channel are arranged at the two ends of the culture solution channel respectively; the lower surface of the runner layer is provided with a first cell culture chamber and a second cell culture chamber which are communicated with the culture solution channel; by adopting a double-layer structure of the flow channel layer and the bottom layer, the micro-fluidic chip has the characteristics of simple structure, convenience in operation, easiness in manufacturing of the chip and the like, and the first cell culture chamber and the second cell culture chamber are separated by the second micro-column; the interaction among different types of cell tissues in the first cell culture chamber and the second cell culture chamber can be realized by utilizing the gaps among the second micro-columns, so that the complex interaction among multiple tissues in the body can be really simulated.

The invention relates to the technical field of bone scaffold materials, and discloses a preparation method and application of a pre-vascularized bone repair scaffold, the preparation method of the pre-vascularized bone repair scaffold comprises the following steps: firstly, obtaining a porous scaffold and carrying out sulfonation treatment to obtain a sulfonated scaffold; then preparing a mixed solution containing gelatin and an extracellular matrix, and adding mesenchymal stem cells and / or endothelial cells to obtain a cell mixed preparation; and finally, contacting the cell mixed preparation with the sulfonated scaffold, and culturing to obtain the sulfonated scaffold. The pre-vascularized bone repair scaffold prepared by the preparation method disclosed by the invention simultaneously has excellent angiogenesis promoting capability and osteogenesis induction characteristic in vitro, and realizes vascularization-ossification synergistic interaction through a positive feedback loop mediated by a paracrine signal network; and a new thought and a new method are expected to be developed for clinical application of large-segment bone defect repair.

The application discloses a kind of biomimetic silk fibroin cartilage scaffolds for cranium defect repair, belong to biomedical engineering technical field.To solve the problem of single structure, low bone formation efficiency and mismatching of mechanical properties and degradation rate of existing cranium repair scaffold, the application provides a kind of scaffold, which includes in order from outside to inside: biomimetic periosteum layer, bone conduction and vascularization layer and cartilage induction layer.Biomimetic periosteum layer is dense nanofiber membrane structure, and plays the role of physical barrier and osteoinduction;Bone conduction and vascularization layer is gradient porous structure with gradually decreasing aperture from outside to inside, aiming to guide the ordered growth of blood vessels and cells, and promote rapid vascularization;Cartilage induction layer is sponge-like microporous structure, used for forming stable cartilage template and starting endochondral ossification.The application simulates the natural bone healing process through structural biomimicry and functional zoning, synergistically promotes vascularization and osteogenesis, and realizes efficient biological repair of cranium defect.

The invention belongs to the technical field of tissue engineering, and relates to a centimeter / decimeter-level three-dimensional vascularization tissue engineering organoid culture device which comprises a culture room, a semipermeable membrane microtube and a peristaltic pump, the semi-permeable membrane microtube is positioned in the inner cavity of the culture device; the inner ends of the culture solution inlet and outlet are respectively communicated with two ends of the semi-permeable membrane microtube; the inner ends of the vascular nutrient solution inlet and outlet are respectively communicated with the inner cavity of the culture chamber; the outer ends of the culture solution inlet and outlet are respectively communicated with a peristaltic pump and a waste liquid collector; the outer end of the blood vessel nutrient solution inlet and outlet is respectively communicated with another peristaltic pump and a waste liquid collector; the vascularization tissue engineering organoid culture system is constructed through the design of double independent circulation systems and adjustable shearing force, oxygen and nutrition can be effectively provided for centimeter / decimeter-level tissue engineering organoid in vitro, metabolites can be taken away, meanwhile, a vascular system can be formed in the cultured tissue engineering organoid, and the tissue engineering organoid can be cultured in vitro. And an efficient and controllable in-vitro culture platform is provided for vascularized tissue engineering organs.

Systems and methods for neural modeling are disclosed. A perfusable microfluidic platform with human hippocampal organoid integration and functional vasculature is disclosed. Vascularized human brain organoids can be developed on a microphysiological platform. The system can include a membrane configured to enable perfusion throughout the membrane. The membrane can couple with a carrier. The system can include the carrier including channels. The channel can be configured to deliver a first set of cells to the membrane through a lumen of the membrane; and deliver a second set of cells to the membrane through an exterior of the membrane. The system can include monitoring components to continuously and non-invasively measure the onset and development of neural oscillations.

Described herein are three-dimensional scaffold compositions and methods for bone repair or regeneration. In some embodiments, the disclosed scaffolds comprise a core portion mimicking a native trabecular bone structure that is surrounded by an exterior portion mimicking a native cortical bone structure. In some embodiments, the scaffolds may be functionalized by mineralization and / or pre-vascularization to promote bone and blood vessel formation.

This invention relates to the field of organoid culture technology, specifically to a vascularized tumor organoid chip. It redesigns the traditional micropillar-separated culture medium and cell culture channels into a dynamically separated structure using acupuncture needles. This avoids the physical limitations of traditional micropillars on blood vessel growth, significantly increases the contact area between vascular cells, and promotes the growth of the vascular network. Simultaneously, the needle insertion channel and reservoir allow for free switching between micro-infusion pump and gravitational potential energy delivery modes. Furthermore, it enables dynamic detection during the co-culture of blood vessels and tumor organoids.

Biologic matrices designed to facilitate wound healing and related methods are disclosed. A matrix comprises a three-dimensional, resorbable collagen scaffold derived from a vascularized portion of a perfusion-decellularized mammalian organ or tissue. The scaffold features a porous structure with a plurality of interconnected pores originating from one or more outer surfaces, which are defined by intact vascular pathways of the perfusion decellularized mammalian organ or tissue. The porous configuration substantially enhances the scaffold's effective surface area, making it at least 5 times greater than that of a non-porous scaffold having equivalent outer dimensions. In certain embodiments, the surface area considering the interconnected pores can be 10 times larger, 15 times larger, or more than the non-porous scaffold of equivalent outer dimensions. The density of the scaffold can range from 2 milligrams per cubic centimeter to 20 milligrams per cubic centimeter, inclusive, further optimizing the matrix's performance for wound healing applications.

The invention provides a surface-modified biological material and a preparation method and application thereof, the surface-modified biological material has a structure of M-(P) n-L-X (formula I), M is a biological material matrix, P is a pre-modified layer, L is a linker, X is a chemical part for promoting repair, n is 0 or 1, n = 0 represents that the material does not have the pre-modified layer P, and n = 1 represents that the material has the pre-modified layer P. The surface modified biological material disclosed by the invention can efficiently and continuously initiate remarkable intracellular calcium ion internal flow, so that osteogenic differentiation, angiogenesis and the like are systematically promoted, and a new material solution is provided for the fields of bone defect repair, vascularization and the like which need precise mechanical signal regulation and control.

The invention provides a preparation method of dynamic connection bone extracellular matrix simulation hydrogel and application of the dynamic connection bone extracellular matrix simulation hydrogel in bone defect repair, and belongs to the technical field of medical hydrogel. L-cysteine ethyl ester functionalized hyaluronic acid and allicin are prepared to form a thiol-disulfide bond dynamic cross-linked network; a sacrificial pre-vascularization template is constructed by combining a collagen thread loaded with a vascular endothelial growth factor, a vascularization guide microchannel is formed by utilizing the enzymolysis characteristic of collagen, the polarization of macrophages is regulated and controlled by hyaluronic acid to inhibit inflammatory response, and the adhesion and osteogenic differentiation of mesenchymal stem cells are promoted by virtue of a functional surface, so that the osteogenic differentiation of the mesenchymal stem cells is promoted. The synergistic effect of vascularization, anti-inflammation and osseointegration is achieved, finally, the dynamic connection bone extracellular matrix simulation hydrogel with a porous interconnection structure and biological activity is formed, and the technical problems that a traditional bone defect repair material is insufficient in vascularization, inflammation interference exists, and osseointegration is poor are solved.

The disclosure provides compositions and methods for directing the growth of blood vessels in a tissue graft. The compositions and methods provide the advantage of directing the growth, size and pattern of blood vessels from the periphery of the graft, which recapitulates or improves the native blood vessel orientation in the host tissue. The compositions comprise a tissue graft that comprises a matrix attached to a barrier. The barrier comprises a porous membrane that permits passage of water and nutrients but blocks blood vessel growth. The methods comprise implanting the tissue graft on a host tissue in a subject and incubating the graft on the host tissue such that blood vessels grow around the edges (periphery) of the barrier or through intentional internal openings in the barrier and into the matrix. The methods can further comprise transplanting the vascularized tissue graft to a second location in the subject. Thus, the methods can be used in a staged implant procedure to create autologous, vascularized bioengineered tissue grafts.

Biologic matrices designed to facilitate wound healing and related methods are disclosed. A matrix comprises a three-dimensional, resorbable collagen scaffold derived from a vascularized portion of a perfusion-decellularized mammalian organ or tissue. The scaffold features a porous structure with a plurality of interconnected pores originating from one or more outer surfaces, which are defined by intact vascular pathways of the perfusion decellularized mammalian organ or tissue. The porous configuration substantially enhances the scaffold's effective surface area, making it at least 5 times greater than that of a non-porous scaffold having equivalent outer dimensions. In certain embodiments, the surface area considering the interconnected pores can be 10 times larger, 15 times larger, or more than the non-porous scaffold of equivalent outer dimensions. The density of the scaffold can range from 2 milligrams per cubic centimeter to 20 milligrams per cubic centimeter, inclusive, further optimizing the matrix's performance for wound healing applications.

Disclosed herein are spinal cord models including a cell scaffold including methacrylated hyaluronic acid (HAMA) and dopamine-modified hyaluronic acid (HA-Cat), and a spinal cord spheroid or organoid or a fragment thereof cultured on the cell scaffold. Said spinal cord spheroids or organoids or fragments thereof can be co-cultured with blood vessel spheroid organoids to form blood-spinal cord barrier models. Also disclosed herein are methods of making and using said models.

This disclosure provides compositions comprising engineered vascularized kidney tissues and methods of making vascularized glomerular kidney tissues. Also provided herein are in vitro kidneys comprising vascularized kidney tissues. Methods of making the compositions and in vitro kidneys and uses thereof are disclosed herein.

The invention relates to a construction method of a perfusion vascularized cervical cancer organoid chip, and relates to the technical field of biology. Comprising the following steps: S1, constructing a cervical cancer organ; s2, mixing the cervical cancer organ small cell cluster, the human umbilical vein endothelial cells and the human embryonic lung fibroblasts in proportion, and centrifugally gathering the mixed cells in a low-adsorption U-shaped plate to form a pre-vascularized cervical cancer organ; s3, re-suspending the pre-vascularized cervical cancer organoid and the human umbilical vein endothelial cells in the fibrous protein hydrogel, transferring the pre-vascularized cervical cancer organoid and the human umbilical vein endothelial cells into the organoid chip, and adding a vascularized cervical cancer organoid culture medium for culture, so that the endothelial cells form perfused blood vessels, and finally obtaining the perfused vascularized cervical cancer organoid chip. The prepared perfusion vascularized cervical cancer organoid can well solve the in-vitro vascularization problem of the organoid, simulates the in-vivo tumor angiogenesis process, is close to the in-vivo real tumor microenvironment, and provides technical support for exploration of cervical cancer disease mechanisms and related treatment.