CN201154962Y

CN201154962Y - Bioreactor for culturing artificial cartilage

Info

Publication number: CN201154962Y
Application number: CNU2007200989832U
Authority: CN
Inventors: 张春秋; 秦晓峰; 武汉; 董心
Original assignee: Tianjin University of Technology
Current assignee: Tianjin University of Technology
Priority date: 2007-12-17
Filing date: 2007-12-17
Publication date: 2008-11-26
Anticipated expiration: 2017-12-17

Abstract

The utility model discloses a biological reactor for artificial cartilage culture and the reactor comprises a reactor frame, a culture room, a culture fluid circulatory system and a pressure transmission mechanism. The biological reactor is characterized in that the bottom part inside the culture room is a carrying platform, above which a rigid loading block is arranged; the pressure transmission mechanism is a group of lever loading mechanisms and the working end of the lever is arranged above the loading block in the culture room, while the power end of the lever is in contact with the dynamic output working face of a piezoelectric ceramic. The biological reactor arranges cultures on the carrying platform in the closed culture room, imposes periodic dynamic loads on the cultures during the culturing period, enlarges the driving stroke by the lever device and the deformation of cartilages cultured can reach 25 percent, thereby providing the mechanical environment needed by the growth in human body for cartilage culture.

Description

The bio-reactor that artificial cartilage is cultivated

[technical field]

The utility model relates to organizational project bio-reactor field, specifically, is a kind of bio-reactor that is used for cartilage tissue engineeredization cultivation.

[background technology]

Articular cartilage defect is one of common disease of surgery, is caused by chronic diseases such as wound, excision, osteoarthritis usually.Clinical manifestation is an intractable pain, joint movement disorder, and severe patient can completely lose function of joint, becomes the one of the main reasons that limb is residual and the labor force loses.The experimental results shows, because the regenerative agent of cartilaginous tissue ability is very limited, the cartilage injury self-regeneration hardly may.Autotransplantation or heteroplastic transplantation also exist bigger restriction and drawback clinically.Current for defect repair provides the transplanting cartilage, cartilage tissue engineered is optimal method.The basic skills of organizational project be with from body or variant cell after vitro culture, amplification, be inoculated on the good biomaterial of a kind of histocompatibility, carry out vitro culture, form certain class tissue, the implant defect merges with host's cartilage then, reaches the purpose of repairing cartilage defect.Wherein cartilage tissue engineered all is to adopt the complex body of different seed cells, timbering material and active factor to cultivate respectively with bone tissue engineer, and cartilaginous tissue also may adopt identical seed cell with osseous tissue, as mesenchymal stem cells MSCs.

Current, along with the development of organizational project, how deepening continuously of seed cell, timbering material and active factor research is cultivated graft and is subjected to more concern in bio-reactor, wherein the mechanical environment of graft culture condition is more and more paid attention to.For cartilage, its live body mechanical environment is very complicated.Suitable mechanical condition be turn out structure, function all with the important factor of the close graft of natural cartilage.Recent years, correlative study person was to different mechanical stimulations, had done big quantity research with the 26S Proteasome Structure and Function of optimizing culture.The domestic investigator of having adopts quiet tension stress that the rat condylar cell propagation effect is studied, and experiment shows that cell proliferation quantity increases with quiet tension stress and raise [West China stomatology magazine, 2003,21 (1), 57-60]; The influence [dissection journal, 2001,32 (4), 385-387] of research air stress to vitro culture chondrocyte secrete cytokines also arranged, effect [the Chinese experimental surgery magazine of centrifugal force in the external structure tissue engineering bone/cartilage.2005,22 (3), 281-283], the periodic current body stress stimulates the experimental study of tissue engineering bone/cartilage differentiation influence [B﹠J damage magazine, 2003,18 (9), 620-622].These loading methods can promote the performance of cell proliferation or function, but and real cartilage stand under load be differentiated.[J Biomech Eng, 2000 such as Mauck; 122 (3): 252-260] think that directly dynamically exerting pressure may be cartilage-derived growth mechanical environment preferably.

The piezoelectric ceramics shifter has compact construction, volume is little, nothing rubs, drive the characteristics sensitive, that the micrometric displacement precision is high, in addition, use the piezoelectric ceramics shifter, because the speed that electromechanical Coupling is carried out is very fast, there is not heating problem, the electricity that influences culturing cell is led with thermal radiation and can be ignored, because the piezoelectric ceramics shifter similar structure that is electrical condenser, so minimum power consumption is arranged, even under high speed and high voltage drive situation, also be like this, therefore, the piezoelectric ceramics shifter can be used as the power resources that artificial cartilage is cultivated dynamic load.Though the displacement that the piezoelectric ceramics shifter produces is less, the amplification by leverage improves load deflection, can satisfy loading (distortion) needs that cartilage is cultivated.As 200 microns of piezoelectric ceramics shifter maximum drive displacements, through 10 times of amplifications of lever, drive displacement can reach 2 millimeters.Thicker cartilage is by 8 mm thick, and its distortion can reach 25%.Usually the mechanical environment of cartilage cultivation is distortion 5%-20%.Can form compact construction, volume is little, driving is sensitive, the micrometric displacement precision is high dynamic loading device like this, add suitable filling system and might form the bio-reactor that cartilage is cultivated.

[utility model content]

The purpose of this utility model is in order to solve existing issue, and the bio-reactor that provides a kind of artificial cartilage to cultivate, this bio-reactor is to adopt the piezoelectric ceramics shifter as the deceleration loading device power resources, in conjunction with leverage drive displacement is amplified, thereby obtain compact construction, volume is little, driving is sensitive, the micrometric displacement precision is high cartilage tissue engineered bio-reactor.

The utility model realizes that the scheme that above-mentioned purpose adopted is the bio-reactor that a kind of artificial cartilage of design is cultivated.It comprises reactor frame, culturing room, and the nutrient solution recycle system and pressure drive mechanism is characterized in that described culturing room inner bottom part is a Stage microscope, the Stage microscope top is provided with a loading blocks; Described pressure drive mechanism is one group of lever load maintainer, and the working end of described lever contacts above the loading blocks upper contact head of culturing room, and the power end of described lever contacts with the power output services face of a piezoelectric ceramics.

The beneficial effects of the utility model are: the utility model compact construction, volume is little, driving is sensitive, micrometric displacement precision height, especially adopt the piezoelectric ceramics shifter as the deceleration loading device power resources, by leverage the load sphere of action is amplified again, can make the distortion of cultivating cartilage reach 25%, thereby meet the required mechanical environment of growth in the body for the cartilage cultivation provides.In addition, pressurizing block can move pressurization mutually about culturing room adopted, and culturing room is totally-enclosed, was poured into and changed the culture environment of liquid function etc. by peristaltic pump, had overcome the deficiencies in the prior art effectively.

[description of drawings]

The bio-reactor front view that Fig. 1 cultivates for artificial cartilage;

The bio-reactor pressure head synoptic diagram that Fig. 2 cultivates for artificial cartilage;

The bioreactor culture chamber sectional view that Fig. 3 cultivates for artificial cartilage;

Fig. 4 is a loading blocks assembly synoptic diagram.

[embodiment]

Below in conjunction with drawings and Examples the utility model is described in detail.

With reference to accompanying

drawing

1,3,4.An embodiment of the present utility model: the bio-reactor that artificial cartilage is cultivated is by reactor frame, culturing room, compositions such as the nutrient solution recycle system and pressure drive mechanism.Described culturing room is a round shape, is provided with nutrient solution inlet 7 and outlet 6.Described Stage microscope is by being threaded in culturing room's inner bottom part, rotatable lifting.Be provided with charging assembly in the described culturing room, described charging assembly is by the loading blocks upper contact head, and contact and folding up at the two intermediary silica gel sealing connection gasket is formed under the loading blocks that spins with it.Described charging assembly is fixing by the fixing catch lid that is screwed in culturing room's oral area by the silica gel sealing connection gasket.Contact is made by rigid material under the described loading blocks.

With reference to accompanying drawing 1,2.The pressure drive mechanism of the bio-reactor that described artificial cartilage is cultivated is one group of lever load maintainer.In the lever load maintainer of described pressure drive mechanism, the balance pivot adjustable length saves land and is connected on the reactor frame.The working end head of described lever has a longitudinal slot, and the longitudinal slot card is placed in worker's shape groove of bar of pressure head, and described pressure head is fixed on the reactor frame.The described piezoelectric ceramics that contacts with the power end of lever is fixed on the reactor frame.

With reference to accompanying drawing 2.It is inverted approximate "T"-shaped that described pressure head is, the bottom be one with the close round platform in rigidity loading blocks upper contact head cross section, the bar of pressure head locate to establish worker's shape groove near the bottom.The bottom and the top work surface of the worker's shape groove on the bar of described pressure head are the arch cambered surface.With the pressure that guarantees lever vertically downward, it is stressed evenly to load block rubber.

For ease of the adjustment of reaction chamber, also be provided with the reaction chamber lifting table on the described reactor frame table top.

Using method of the present utility model is:

At first to culturing room's sterilization, the cartilaginous tissue 14 that will cultivate under aseptic condition then is inoculated on the Stage microscope 13 of culturing room inside.

Earlier silica gel sealing connection gasket 12 is snapped in the threaded rod bottom of rigidity loading blocks upper contact head, secondly silica gel sealing connection gasket 12 is stepped up, then aforementioned assembly to be assembled by fixing catch lid 5 and culturing room's shell 7 up and down between the contact in loading blocks thereby contact 13 under rigidity loading blocks upper contact head 4 and the rigidity loading blocks is screwed.Aforesaid operations is all operated under aseptic condition.

In addition, in the lever load maintainer, the working end head of lever 9 has a longitudinal slot, and the longitudinal slot card is placed in worker's shape groove 16 of pressure head bar.

Then the culturing room that assembles is placed on the lifting table 8 of framework 1 table top, regulates lifting table, make the last upper contact head upper surface of rigidity loading blocks contact with the lower surface of the circular platform of pressure head 3.The pretension screw 2 of adjustment (adjusting) lever fulcrum 10 applies preload to artificial cartilage.

After above-mentioned work is finished, under computer control, give the piezoelectric ceramics electrical signal that 11 inputs require, piezoelectric ceramics 11 produces regular distortion under action of electric signals, the distortion of piezoelectric ceramics is by the amplification of lever 9, (pressure head 3 has guide effect in this process to act on the rigidity loading blocks by pressure head 3, make the power that acts on the rigidity loading blocks remain vertical direction), thus the displacement that makes the rigidity loading blocks produce vertical direction realizes the cartilaginous tissue of cultivating is loaded.

Claims

1, a kind of bio-reactor of artificial cartilage cultivation comprises reactor frame, culturing room, and the nutrient solution recycle system and pressure drive mechanism is characterized in that described culturing room inner bottom part is a Stage microscope, the Stage microscope top is provided with a loading blocks; Described pressure drive mechanism is one group of lever load maintainer, and the working end of described lever contacts above the loading blocks upper contact head of culturing room, and the power end of described lever contacts with the power output services face of a piezoelectric ceramics.

2, the bio-reactor of artificial cartilage cultivation according to claim 1 is characterized in that described culturing room is a round shape, is provided with the nutrient solution entrance and exit; The Stage microscope of described culturing room inner bottom part connects by the screw thread liftable; Be provided with charging assembly in the described culturing room, described charging assembly is by the loading blocks upper contact head, and contact and folding up at the two intermediary silica gel sealing connection gasket is formed under the loading blocks that spins with it; Described charging assembly is fixing by the fixing catch lid that is screwed in culturing room's oral area by the silica gel sealing connection gasket.

3, the bio-reactor of artificial cartilage cultivation according to claim 2 is characterized in that contact is made by rigid material under the described loading blocks.

4, the bio-reactor of cultivating according to claim 1 or 2 or 3 described artificial cartilages, the described balance pivot adjustable length that it is characterized in that described pressure drive mechanism saves land and is connected on the reactor frame; The working end head of described lever has a longitudinal slot, and the longitudinal slot card is placed in worker's shape groove of bar of pressure head, and described pressure head is fixed on the reactor frame; The described piezoelectric ceramics that contacts with the power end of lever is fixed on the reactor frame.

5, the bio-reactor cultivated of artificial cartilage according to claim 4 is characterized in that described pressure head is inverted approximate "T"-shaped, and the bottom is a round platform, the bar of pressure head establish worker's shape groove near the place, bottom.

6, the bio-reactor of artificial cartilage cultivation according to claim 5 is characterized in that the bottom and the top work surface of the worker's shape groove on the described pressure head bar is the arch cambered surface.

7, the bio-reactor of artificial cartilage cultivation according to claim 4 is characterized in that described reactor frame table top is provided with the reaction chamber lifting table.