CN103690273A - In vivo bioreactor - Google Patents

Abstract

A bioreactor in the body, including a catheter, the outlet end of the catheter is arranged in the hollow cavity of the artificial bone material, the end of the catheter is fixed on the artificial bone material with a Kirschner wire, and a fixing net for fixing is arranged on the periphery of the bone defect, The inlet end of the catheter is connected to the outlet of the infusion port, and the inlet of the infusion port is connected to the medical constant flow air bag power pump; the plasma in the medical constant flow air bag power pump passes through the blood transfusion port and is supplied to the body by the catheter; it solves the problem of nutrition in the material cell complex. It provides a good device for the treatment of large bone defects, and has the characteristics of simple structure and good effect.

Description

An in vivo bioreactor

technical field

The invention belongs to the field of medical technology, and specifically relates to an in vivo bioreactor, which is suitable for the repair and reconstruction of long-segment bone defects caused by various reasons, and makes the biological healing of large-segment bone defects possible.

Background technique

Trauma, infection, and resection of bone tumors often lead to severe bone tissue defects, especially large (more than 20 mm) bone defects, which greatly increase the difficulty of treatment, resulting in a series of high disability rates, long disability time, and difficulties in later treatment. question. The repair and functional reconstruction of large bone defects has always been a difficult problem and research hotspot in orthopedics. At present, allogeneic bone and vascularized autologous bone transplantation are mostly used to treat large segmental bone defects clinically, but there are still risks of immune rejection and disease transmission in the treatment of large segmental bone defects with allogeneic bone. Repairing large-segment defects with vascularized autologous bone graft requires complex operations at both the recipient and donor sites, which makes the patient bear a heavy surgical burden. Moreover, the amount of autologous bone donor is limited after all. In recent years, bone tissue engineering technology has developed rapidly, and tissue engineered bone provides an ideal repair method for bone defects. Tissue-engineered bone has shown unprecedented advantages in the repair of bone defects due to its unlimited source and similar or better biological functions than autologous bone.

At the same time, bioreactors play an irreplaceable role in the field of tissue engineering. At present, from the perspective of bionics, many scholars use in vitro bioreactors to simulate the internal environment of tissues or organs in vivo, and conduct research on the construction of tissue engineered bones. Nutrients are evenly scattered into the interior of the three-dimensional scaffold material through the rotation of the culture chamber and the perfusion of the central pipeline to continuously supply the nutrients required by the cells. To a certain extent, it solves the nutrient supply inside the material. However, there is still a large difference between the current in vitro bioreactor and the actual in vivo environment, which cannot provide a complete in vivo microenvironment, and has not solved the problem of vascularization of tissue engineered bone. Therefore, it can only maintain the survival of the cells inside the material in vitro. When the material is transplanted into the bone defect in the body, it takes days or even weeks for the blood vessels to grow in, and the cells can only tolerate hypoxia for a few hours, and the nutrient supply of the early cells is only a few hours. It is supplied by the tissue fluid of the body, and the diffusion force of oxygen is limited to within 200 μm. The cells inside the final material are still not viable.

Contents of the invention

In order to overcome the deficiencies of the above-mentioned prior art, the object of the present invention is to provide an in vivo bioreactor, which solves the problems of nutrient supply and blood vessel ingrowth in the material cell complex, and provides a good solution for the treatment of large bone defects. The device has the characteristics of simple structure and good effect.

In order to achieve the above object, the technical solution adopted by the present invention is: a bioreactor in the body, including a catheter, the outlet end of the catheter is arranged in the hollow cavity of the artificial bone material, and the end of the catheter is fixed on the artificial bone material with a Kirschner wire , the periphery of the bone defect is provided with a fixed net for fixation, the inlet of the catheter is connected with the outlet of the infusion port, and the inlet of the infusion port is connected with a medical constant flow airbag power pump.

The infusion port is connected with the infusion port seat, and the infusion port separates the two systems of in vivo culture and in vitro perfusion. The infusion port is used for separation, which greatly reduces the possibility of wound contamination.

The fixed net adopts titanium net.

The fixed net is composed of two semicircular nets, and the two semicircular nets are fixed with screws.

The artificial bone material adopts a porous bioceramic material with a hollow blind end.

The beneficial effects of the present invention are:

The medical constant flow air bag power pump is filled with artificial plasma, which contains various nutrients and related cytokines required for cell survival, which is beneficial to the vascularization and osteogenesis of cell material complexes.

The connection of the catheter to the artificial bone material is secured by a thin Kirschner wire. The cell-material composite is transplanted into the bone defect, and the two ends of the bone defect are fixed by internal fixation or external fixation, and a thin layer of titanium mesh is attached around the artificial bone material to prevent the material from shifting and falling. Screws fix the titanium mesh at both ends of the bone defect,

The invention provides a complete in vivo environment for the artificial bone material, ensures that after the material is implanted into a bone defect in the body, it can still continuously provide nutrition for the cells inside the material and can promote the vascularization and osteogenesis of the material. On the basis of overcoming the defects of the existing technology, it provides a new technical means for the clinical treatment of large segmental bone defects.

Description of drawings

Figure 1 is a schematic diagram of the overall structure of the present invention.

Fig. 2 is a structural diagram of the artificial bone material of the present invention.

Fig. 3 is a schematic structural diagram of the fixed net of the present invention.

Detailed ways

The present invention will be described in further detail below in conjunction with the accompanying drawings.

Referring to Figures 1, 2, and 3, a bioreactor in vivo includes a catheter 1, the outlet end of the catheter 1 is set in the hollow cavity 5 of the artificial bone material 4, and the end of the catheter is fixed on the artificial bone material 4 with a Keshi needle 3 Above, the bone defect is provided with a fixing net 6 for fixing, the inlet end of the catheter 1 is connected to the outlet of the infusion port 2, and the inlet of the infusion port 2 is connected to the medical constant flow airbag power pump 8.

The infusion port is connected with the infusion port seat, and the infusion port separates the two systems of in vivo culture and in vitro perfusion. The infusion port is used for separation, which greatly reduces the possibility of wound contamination.

Described fixed net 6 is made up of two semicircular nets, and two semicircular nets are fixed with screw 7.

Described fixed net 6 adopts titanium net.

The artificial bone material adopts a porous bioceramic material with a hollow blind end.

A small circular hole was drilled at the proximal end of the bone defect 2cm away from the defect to reach the bone marrow cavity. The end of the catheter connected to the infusion port is inserted into this small hole, and extends to the bone defect through the bone marrow cavity, and then the end of the catheter is inserted into the hollow structure of the artificial bone material, and the pipe wall of the catheter is connected to the artificial bone material through a small Kirschner wire to fix. The cell-material composite is transplanted into the bone defect, and the two ends of the bone defect are fixed by internal fixation or external fixation, and a thin layer of titanium mesh is attached around the material (3D printing technology, the mesh size is 0.5cmX0.5cm square) , to prevent the material from shifting and falling, the titanium mesh is fixed on both ends of the bone defect with two upper and lower screws, and the cell-material complex is wrapped by soft tissues such as surrounding muscles. The other end of the infusion port catheter is connected with an infusion port seat to fix it under the skin. After cleaning the wound, the wound is closed layer by layer, the skin is sutured, and only a circular protrusion can be touched on the body surface, and a non-injured needle is vertically punctured into the reservoir of the injection port of the infusion port. The atraumatic needle is connected to a medical constant flow balloon powered pump. The combination of this whole set of structures constitutes the in vivo bioreactor. This type of bioreactor not only provides the nutritional supply of a large section of tissue-engineered bone in the body, but also allows the blood vessels in the surrounding muscle soft tissue to grow inward continuously. The material is made to form bone and blood vessels simultaneously from the inner and outer layers, which accelerates the healing of the cell-material composite and bone defects at both ends.

The working principle of the present invention:

The plasma in the medical constant flow air bag power pump is supplied to the body through the catheter through the blood transfusion port.

1) The medical constant flow airbag power pump is filled with artificial plasma, which contains various nutrients and related cytokines required for cell survival, which is beneficial to the vascularization and osteogenesis of cell-material complexes.

2) Strictly control the flow rate and flow rate during perfusion to 2.0ml/h, because the perfused artificial plasma cannot be completely absorbed by the cells after flowing through the porous artificial bone material, so the excess plasma will be absorbed by the surrounding muscle soft tissue. The study found that the average crystalloid penetration rate of the surrounding soft tissue was 0.125ml/(h·cm ² ).

3) Two weeks of continuous perfusion is enough. The study found that the pure artificial bone material wrapped in soft tissue has grown blood vessels into the deep part of the material within two weeks. Therefore, after two weeks of perfusion, a large number of blood vessels had grown into the material, enough to provide nutrients for the remaining cells.

4) After two weeks, the perfusion was stopped, and the infusion port, Kirschner wire and thin titanium mesh were completely removed.

The in vivo bioreactor of the present invention can completely overcome the defects of the prior art, and ensure the simultaneous vascularization and osteogenesis of the inner and outer layers of the artificial bone material, which not only provides a new technical means for the treatment of large bone defects, but also provides Clinical treatment creates new ways of thinking.

Claims (5)

1. an in-vivo biological reactor, include conduit (1), it is characterized in that, the port of export of conduit (1) is located in the cavity (5) of artificial bone (4), Kirschner wire for catheter tip (3) is fixed on artificial bone (4), outside the damaged place of bone, be arranged with for fixing fixed network (6), conduit (1) arrival end is connected with the outlet of transfusion port (2), and the entrance of transfusion port (2) is connected with medical constant flow rate air bag kinetic pump (8).

2. a kind of in-vivo biological reactor according to claim 1, is characterized in that, described transfusion port is connected with transfusion port seat, and transfusion port is by culturing in vivo and two system partitionings of external counterpulsation.

3. a kind of in-vivo biological reactor according to claim 1, is characterized in that, described fixed network (6) is comprised of two semicircular nets, two semicircular for net screw (7) fixing.

4. a kind of in-vivo biological reactor according to claim 1, is characterized in that, described fixed network (6) adopts titanium net.

5. a kind of in-vivo biological reactor according to claim 1, is characterized in that, described artificial bone adopts the porous bio-ceramic material of cecum hollow.

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