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Problems solved by technology
[0005] Although related technologies have been developed for many years, there are still significant deficiencies: 1. The culture process of MSCs induced differentiation is very cumbersome, and when MSCs are induced to differentiate into different types of cells, different culture systems are required
The entire cultivation process takes a long time, which greatly increases the risk of contamination
3. Using the method of planting seed cells on the surface of scaffold materials to construct artificial implants, it is difficult to accurately arrange the cells growing on the surface of the material, resulting in the formation of artificial implants with chaotic structures and insufficient functions
Method used
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preparation example Construction
[0260] The methods of the present invention for making constructs are compatible with other bioprinting methods known in the art. For example, the method of the present invention can be used in bioprinters developed by Cyfuse, Organovo and EnvisionTEC. Three main types of bioprinters have been developed, namely, inkjet bioprinters, extrusion bioprinters and laser-assisted bioprinters (see Murph SV and Atala A. (2014) Nature Biotechnology, 32(8): 773 -785). Alternatively, the methods of the present invention for making constructs can be used in bioprinting methods using automated or non-automated mechanical processes (rather than printers), or in bioprinting using manual placement or manual deposition methods (e.g. using pipettes) method. In certain preferred embodiments, bioprinting is performed by inkjet. In certain preferred embodiments, bioprinting is performed by extrusion. In certain preferred embodiments, bioprinting is performed by manual placement or manual deposit...
specific Embodiment approach
[0310] The invention will now be described with reference to the following examples, which are intended to illustrate the invention, but not to limit it.
[0311] Reagents, kits or instruments whose sources are not specified in the examples are all conventional products commercially available on the market. Those skilled in the art understand that the examples describe the present invention by way of example and are not intended to limit the scope of the claimed invention.
Embodiment 1
[0312] Embodiment 1. The preparation of biological brick
[0313] This example provides an exemplary method of making a biobrick. The preparation method of the bio-brick should be carried out under sterile conditions. In addition, if the bio-brick is intended to be applied to the human body, the biosafety level of its preparation method should reach the GMP workshop level.
[0314] The instrument used in this method is a granulator (BUCHI, Encapsulator, B-395 Pro), and the diameters of the concentric nozzles it is equipped with are as follows: the inner layer nozzle, 200 μm; the outer layer nozzle, 300 μm.
[0315] The materials used in this method are as follows:
[0316] (1) Materials used to prepare the nuclear layer
[0317] Type I collagen: 4mg / ml, neutralized with sterile 1M NaOH;
[0318] Sodium alginate: Dissolve and dilute with deionized water;
[0319] Vascular endothelial growth factor VEGF;
[0320] Type I collagen was mixed with 2% (w / v) (ie, 2 g / 100 ml, the...
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Abstract
The invention provides a biobrick, comprising MSCs, a core layer wrapping the MSCs and a shell layer encapsulating the core layer, wherein the core layer and the shell layer are independently prepared from a biodegradable material and the core layer contains an inducing factor capable of inducing differentiation of MSCs into osteoblasts or bone. The invention also provides another biobrick, comprising MSCs, a core layer wrapping the MSCs and a shell layer encapsulating the core layer, wherein the core layer and the shell layer are independently prepared from a biodegradable material and the core layer contains an inducing factor capable of inducing differentiation of MSCs into chondroblasts or cartilage. The invention further provides a method for preparing a composite structure containing bone and cartilage. The composite structure comprises the above-mentioned two biobricks. The invention also provides the composite structure containing bone and cartilage prepared by using the method.
Description
technical field [0001] The invention relates to the technical fields of biology, regenerative medicine, bioprinting (such as 3D bioprinting), tissue engineering and the like. In particular, the present invention provides a biobrick comprising mesenchymal stem cells (MSCs), a nuclear layer encapsulating the MSC cells, and a shell encapsulating the nuclear layer, wherein the core layer and the shell layer Each is independently made of a biodegradable material, and the nuclear layer contains induction factors that induce differentiation of MSCs into osteoblasts or bone. The present invention also provides a biobrick comprising mesenchymal stem cells (MSCs), a nuclear layer wrapping the MSC cells, and a shell layer encapsulating the nuclear layer, wherein the nuclear layer and the shell layer are independent The ground is made of biodegradable materials, and the nuclear layer contains inducing factors that induce MSCs to differentiate into chondrogenic or cartilage cells. The pr...
Claims
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