CN207502096U - A set of mechanics parameter for engineering blood vessel culture monitors system - Google Patents

A set of mechanics parameter for engineering blood vessel culture monitors system Download PDF

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Publication number
CN207502096U
CN207502096U CN201721470909.9U CN201721470909U CN207502096U CN 207502096 U CN207502096 U CN 207502096U CN 201721470909 U CN201721470909 U CN 201721470909U CN 207502096 U CN207502096 U CN 207502096U
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silicone tube
segment
blood vessel
glass reactor
bioreactor
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林展翼
文章
吴岳恒
马文韬
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Guangdong General Hospital Guangdong Academy of Medical Sciences
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Guangdong General Hospital Guangdong Academy of Medical Sciences
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Abstract

The utility model is related to a set of mechanics parameters for engineering blood vessel culture to monitor system, bioreactor culture system is equipped with glass reactor, first segment silicone tube runs through glass reactor, impulsive motion bioreactor dynamical system is connected to one end of first segment silicone tube by second segment silicone tube, the entrance of liquid storing bag is connected to the other end of first segment silicone tube by third section silicone tube, and the outlet of liquid storing bag is connected to impulsive motion bioreactor dynamical system by the 4th section of silicone tube;Second segment silicone tube passes through laser diameter measuring instrument, and pressure sensor is connect with second segment silicone tube, and pressure sensor and laser diameter measuring instrument are connect with data collecting system signal;Seed cell is inoculated on biocompatible materials, the both ends of wrapping layer are equipped with artificial blood vessel.This monitoring system can accurately high frequency monitoring silicone tube flow field pressure and silicone tube deformation, belong to medical treatment and experimental study equipment technical field.

Description

A set of mechanics parameter for engineering blood vessel culture monitors system
Technical field
The utility model is related to medical treatment and experimental study equipment technical field more particularly to it is a set of be used for organizational project blood The mechanics parameter monitoring system of pipe culture.
Background technology
With the process of China human mortality aging, the incidence of the chronic diseases such as hypertension, diabetes is increasing, thus Caused chronic vascular disease is also in the trend risen year by year, and the demand to vasotransplantation increases year by year, wherein coronary artery With small-bore (≤6mm in peripheral blood vessel by-pass operation) demand of vasotransplantation is very big.Allosome biology blood vessel is immune because easily causing Repel and eventually lead to angiemphraxis;Autologous vein can bring certain injury, length and caliber in materials process to sufferers themselves The limited source of suitable self nonessential blood vessel, in addition the Most patients age itself relatively bigger than normal lead to vascular conditions mostly It is bad.The artificial synthesized blood vessel such as materials such as terylene, polytetrafluoroethylene (PTFE) as foreign matter can cause Chronic immune rejection, infection and Embolism, with the extension of time, tube chamber patency rate declines, if prolonged application anticoagulation has certain side effect again, therefore organize Engineered blood vessels (TEBV) are as new research hotspot.
Engineering blood vessel is since it is with good physical behavior;Abundance, it is cheap;Preferable antithrombotic, group Compatibility, the secretion biological functions such as bioactive substance are knitted, thus before having a vast market application in vascular transplant Scape.Also, when building TEBV in vitro, artificially applying suitable mechanical stimulation becomes the common recognition of people.Reasonable utilization pulsation life Object reactor simulates the hydrodynamics environment of body vessel in vitro, and being built into vitro can self extracellular matrix secretion, tool There are certain mechanical strength, the fully functional TEBV for being capable of self reconstruct.
The research of engineering blood vessel is external apparent further both at home and abroad in fast development, but in terms of industrialization. Domestic engineering blood vessel research is still in the laboratory research stage, and industrialization level is relatively low, and study on the industrialization is very urgent.
On the whole, most engineering blood vessel dynamic cultivation systems, the mechanical stimulation suffered by cell are big at present Quantitative evaluation is not all obtained, but is carried out with the physiological parameter (such as blood pressure and heart rate) or silicone tube deformation size of power source indirect Assessment can not directly embody the stress distribution of smooth muscle cell during tissue engineering vessel, and if to culture parameters into It is difficult to predict limit pair to a certain extent for the change of suffered mechanical stimulation after row (power source parameter or silicone tube performance) adjustment The improvement of cultivating system or parameter.Therefore, it is to have quite meaning to establish a set of monitoring system for engineering blood vessel culture Justice.
Now studies have reported that, the monitoring method of engineering blood vessel culture includes:Transmit computed tomography scanning;High-speed camera is caught Catch silicone tube deformation;Pressure sensor surveys fluid hydraulic pressure in silicone tube.But the above-mentioned detection for engineering blood vessel culture Method, sensitivity is not high, and the parameter error of acquisition is larger, and can not calculate the stress distribution of silicone tube, can not assess cell Suffered mechanical stimulation.It can not determine suitable mechanics parameter, making it difficult to simulate incentive condition in individual cell level, limit point Sub horizontal research, and it is difficult to predict the change of suffered mechanical stimulation after change culture parameters, constrain to cultivating system or ginseng Several improvement.
Utility model content
For the technical problems in the prior art, the purpose of this utility model is:It provides a set of for organizational project The mechanics parameter monitoring system of blood vessel culture accurately can monitor the deformation of silicone tube flow field pressure and silicone tube by high frequency.
In order to achieve the above object, the utility model adopts the following technical solution:
A set of mechanics parameter for engineering blood vessel culture monitors system, including impulsive motion bioreactor dynamical system System, laser diameter measuring instrument, pressure sensor, data collecting system, bioreactor culture system, liquid storing bag;Bioreactor is trained The system of supporting is equipped with glass reactor, and glass reactor is equipped with first segment silicone tube, and first segment silicone tube runs through glass reactor, The outlet of impulsive motion bioreactor dynamical system is connected to one end of first segment silicone tube by second segment silicone tube, liquid storing bag Entrance is connected to the other end of first segment silicone tube by third section silicone tube, and the outlet of liquid storing bag is connected by the 4th section of silicone tube It is connected on the entrance of impulsive motion bioreactor dynamical system;Second segment silicone tube passes through laser diameter measuring instrument, pressure sensor and second Section silicone tube connection, pressure sensor and laser diameter measuring instrument are connect with data collecting system signal;It is set on first segment silicone tube There is wrapping layer, wrapping layer is the biocompatible materials of degradability, and seed cell, wrapping layer are inoculated on biocompatible materials Both ends be equipped with artificial blood vessel.
It is further:Liquid storing bag is flexible pouch.
It is further:Laser diameter measuring instrument is equipped with calibrates slot for what second segment silicone tube passed through.
It is further:Bioreactor culture system includes glass reactor, silica gel lid, changes liquid pipe and permeability cell;Silicon Jiao Gai is covered on glass reactor, changes liquid pipe and permeability cell is inserted into glass reactor.
It is further:Two glass pipes being provided symmetrically on the glass wall of glass reactor.
It is further:Changing liquid pipe has one, and permeability cell has two.
It is further:First segment silicone tube, second segment silicone tube, third section silicone tube are integrated.
Generally speaking, the utility model has the following advantages that:
This monitoring system measures for the culture parameters of engineering blood vessel, can be during engineering blood vessel culture Monitor corresponding mechanics parameter, can accurately high frequency monitoring silicone tube flow field pressure and silicone tube deformation.The monitoring system Can steady and continuous operation, monitor relevant parameter, so as to calculate the stress distribution using silicone tube as mechanotransduction medium, quantify Assess the mechanical stimulation suffered by seed cell in incubation.This monitoring system flexibility is big, easily according to required measurement Parameter carrys out swap modules.
Description of the drawings
Fig. 1 is the principle schematic diagram of this monitoring system.
Fig. 2 is the principle schematic diagram of bioreactor culture system.
Fig. 3 is the principle schematic diagram of laser diameter measuring instrument.
Fig. 4 is the schematic diagram of first segment silicone tube and wrapping layer.
Specific embodiment
Below in conjunction with the drawings and specific embodiments, the utility model is described in more detail.
It is now attached to what is occurred in Figure of description for the ease of uniformly checking each reference numeral inside Figure of description Icon note is unitedly described as follows:
1 is impulsive motion bioreactor dynamical system, and 2 be pressure sensor, and 3 be laser diameter measuring instrument, and 4 be data acquisition system System, 5 be bioreactor culture system, and 6 be liquid storing bag, and 7 be first segment silicone tube, and 8 be second segment silicone tube, and 9 be third section Silicone tube, 10 be the 4th section of silicone tube, and 11 be glass reactor, and 12 be wrapping layer, and 13 be silica gel lid, and 14 be artificial blood vessel, 15 For permeability cell, 16 is change liquid pipe, and 17 be glass pipe, and 18 is calibrate slot.
With reference to shown in Fig. 1 to Fig. 4, a set of mechanics parameter for engineering blood vessel culture monitors system, including pulsation Bioreactor dynamical system, laser diameter measuring instrument, pressure sensor, data collecting system, bioreactor culture system, liquid storage Bag.Bioreactor culture system is equipped with glass reactor, and glass reactor is equipped with first segment silicone tube, first segment silicone tube Through glass reactor, first segment silicone tube is horizontal positioned, and first segment silicone tube passes through glass anti-from the side of glass reactor Answer the opposite side of device.The outlet of impulsive motion bioreactor dynamical system is connected to first segment silicone tube by second segment silicone tube One end, the entrance of liquid storing bag are connected to the other end of first segment silicone tube by third section silicone tube;That is second segment silicone tube One end is connected to the outlet of impulsive motion bioreactor dynamical system, and the other end of second segment silicone tube is connected to first segment silicone tube One end, one end of third section silicone tube is connected to the entrance of liquid storing bag, and the other end of third section silicone tube is connected to first segment The other end of silicone tube.The outlet of liquid storing bag is connected to entering for impulsive motion bioreactor dynamical system by the 4th section of silicone tube Mouthful;One end of i.e. the 4th section silicone tube is connected to the outlet of liquid storing bag, and the other end of the 4th section of silicone tube is connected to pulsation biology The entrance of reactor dynamical system.Second segment silicone tube passes through laser diameter measuring instrument, and pressure sensor is connect with second segment silicone tube, Pressure sensor is used for acquiring the fluid field pressure signal of second segment silicone tube, and laser diameter measuring instrument is used for monitoring and acquiring second in real time The deformation signal of section silicone tube.Pressure sensor and laser diameter measuring instrument are connect with data collecting system signal.First segment silica gel Pipe is equipped with wrapping layer, and wrapping layer is the biocompatible materials of degradability, and seed cell is inoculated on biocompatible materials, The both ends of wrapping layer are equipped with artificial blood vessel;Wrapping layer is located at the inside of glass reactor, and wrapping layer is that degradable biological is compatible Property artificial material.
First segment silicone tube, second segment silicone tube, third section silicone tube are integrated, i.e., they are a whole silicone tubes, For convenience of description, three sections are divided into illustrate.
The principle of the utility model:With reference to shown in Fig. 1, under the effect of impulsive motion bioreactor dynamical system, in silicone tube Liquid pulsation flows in a counterclockwise direction, form pulsation liquid, nutritious liquid in glass reactor.Pulsation biological respinse The beating stream energy that device dynamical system is formed is converted into the form of energy of silicone tube deformation, and final silicone tube can be expanded or be shunk, So as to form mechanical stimulation, the seed cell on the biocompatible materials of degradability is stimulated, then seed cell proliferation, secretion Extracellular matrix forms engineering blood vessel, and during engineering blood vessel is formed, biocompatibility artificial material will drop It takes off, it should be noted that the artificial blood vessel at wrapping layer both ends does not link together with engineering blood vessel, but is organizing After engineered blood vessels are formed, the artificial blood vessel at engineering blood vessel both ends is removed.This monitoring system can be trained in engineering blood vessel Corresponding mechanics parameter is monitored in foster process, accurately can monitor blood vessel glass reactor flow field pressure and power in real time by high frequency The deformation of transmitting medium is learned, that is, monitors the deformation of silicone tube flow field pressure and silicone tube.High-precision pressure sensor is with swashing Pressure and deformation on light caliper acquisition silicone tube, acquire corresponding signal by data collecting system, then pass to electronics Key parameter is monitored on computer, so as to calculate the stress distribution using silicone tube as mechanotransduction medium, quantitative evaluation tissue Mechanical stimulation in engineered blood vessels incubation suffered by cell.
With reference to shown in Fig. 3, laser diameter measuring instrument is equipped with calibrates slot for what second segment silicone tube passed through.That is laser diameter measuring instrument On have and calibrate slot, second segment silicone tube is calibrated slot from this and is passed through, and then laser diameter measuring instrument can monitor the deformation of silicone tube.
Bioreactor culture system includes glass reactor, silica gel lid, changes liquid pipe and permeability cell;Silica gel lid is covered in glass On reactor, change liquid pipe and permeability cell is inserted into glass reactor.Nutrient solution in glass reactor can be replaced by changing liquid pipe, Permeability cell can be supplied oxygen into glass reactor.Changing liquid pipe has one, and permeability cell has two.
With reference to shown in Fig. 2, two glass pipes being provided symmetrically on the glass wall of glass reactor.First segment silica gel It is penetrated in glass reactor in Guan Congyi glass pipe, is then pierced by glass reactor from another glass pipe.
The impulsive motion bioreactor dynamical system for generating different pulsatile flow fields is selected, a variety of condition of culture can be provided, from And facilitate monitoring under different pulsatile flow fields or under the training mode of same pulsatile flow field different condition, engineering blood vessel (TEBV) mechanical stimulation in incubation suffered by seed cell, so as to find out most advantageous training method.It will be thin Mechanical stimulation suffered by born of the same parents quantifies, and contributes to researcher that the relevant parameter of engineering blood vessel culture is applied to cell monolayer training It supports, effect of the mechanical stimulation to cell is studied in monolayer cell culture, shearing force can also be added in culture systems, for The mechanism of Endothelial Cell and smooth muscle cell is critically important.
By the pressure of pulsatile flow field, first segment silicone tube in glass reactor is promoted to deform upon, is attached at so as to allow Smooth muscle cell (seed cell) on first segment silicone tube is by mechanical stimulation, then again by adjusting impulsive motion bioreactor The parameters such as the pulsating waveform of dynamical system, frequency, pressure size, it is possible to pulsatile flow field is effectively controlled, it is anti-so as to change glass Answer the Deformation Law of first segment silicone tube in device.
Liquid storing bag uses flexible pouch, and indirect with contacting external air rigid collecting device, and monitoring system is in addition to glass Reactor is supplied oxygen to smooth muscle cell other than (sterile) in itself, and other parts are isolated from the outside world, in itself enclosed system. Flexible-belt is suspended on certain altitude, to provide hydrostatic pressing in silicone tube, ensures the pressure that impulsive motion bioreactor dynamical system generates Power makes silicone tube generate enough deformation.
The entirely autonomous design of this monitoring system, bioreactor culture system main material are transparent glass, and shape is passed through Special designing, final hand blown form.Its shape, size design consider seed cell inoculum density, total number of cells, required The factors such as ratio of culture medium, required filtrated air.Silica gel lid passes through special designing, has good leakproofness, and can filter Air ensures sterile air in glass reactor, and can carry out the replacement of culture solution by it.This monitoring system monitors in real time Pulsatile flow field pressure and silicone tube diameter change under difference pulsation kinetic parameter, and the distribution of silica gel tube wall stress is calculated, further Assess the mechanical stimulation suffered by cell.In addition, glass reactor is suitable for the silicone tube of different bores, it is possible to turn out The engineering blood vessel of different-diameter.
Monitoring system is suitable for different types of impulsive motion bioreactor dynamical system, it is possible to detect different Pulsating Flows Smooth muscle cell pressure in TEBV and silicone tube diameter change off field.The monitoring system not only can be only used for tissue work Journey blood vessel is studied, and effective monitoring can be realized in most of organizational project cultures for needing mechanical stimulation.And the systematic comparison Flexibly, required module can freely be increased.
In performance test, entire monitoring system being capable of stable operation at least 4 weeks.Each position is combined closely, and is not occurred Pollution and leakage, and the monitoring accuracy for monitoring system is controlled always in ± 2 μm.Silicone tube shape control 2% to 5% it Between, be conducive to the culture of engineering blood vessel.It is non-toxic to cell since the connection of all pipelines is all medical grade silicone pipe. Fluid inherently water, the minimum liquid of viscosity, so the power of impulsive motion bioreactor dynamical system can be given with the accurate transmission Silicone tube in glass reactor.
Above-described embodiment is the preferable embodiment of the utility model, but the embodiment of the utility model is not by above-mentioned The limitation of embodiment, the change made under other any Spirit Essences and principle without departing from the utility model are modified, are replaced In generation, simplifies combination, should be equivalent substitute mode, is included within the scope of protection of the utility model.

Claims (7)

1. a set of mechanics parameter for engineering blood vessel culture monitors system, it is characterised in that:Including biological respinse of pulsing Device dynamical system, laser diameter measuring instrument, pressure sensor, data collecting system, bioreactor culture system, liquid storing bag;Biology Bioreactor culture system is equipped with glass reactor, and glass reactor is equipped with first segment silicone tube, and first segment silicone tube runs through glass Glass reactor, the outlet of impulsive motion bioreactor dynamical system are connected to the one of first segment silicone tube by second segment silicone tube End, the entrance of liquid storing bag are connected to the other end of first segment silicone tube by third section silicone tube, and the outlet of liquid storing bag passes through the Four sections of silicone tubes are connected to the entrance of impulsive motion bioreactor dynamical system;Second segment silicone tube passes through laser diameter measuring instrument, pressure Sensor is connect with second segment silicone tube, and pressure sensor and laser diameter measuring instrument are connect with data collecting system signal;First Section silicone tube is equipped with wrapping layer, and wrapping layer is the biocompatible materials of degradability, is inoculated with planting on biocompatible materials Daughter cell, the both ends of wrapping layer are equipped with artificial blood vessel.
2. a set of mechanics parameter for engineering blood vessel culture described in accordance with the claim 1 monitors system, feature exists In:Liquid storing bag is flexible pouch.
3. a set of mechanics parameter for engineering blood vessel culture described in accordance with the claim 1 monitors system, feature exists In:Laser diameter measuring instrument is equipped with calibrates slot for what second segment silicone tube passed through.
4. a set of mechanics parameter for engineering blood vessel culture described in accordance with the claim 1 monitors system, feature exists In:Bioreactor culture system includes glass reactor, silica gel lid, changes liquid pipe and permeability cell;Silica gel lid is covered to react in glass On device, change liquid pipe and permeability cell is inserted into glass reactor.
5. a set of mechanics parameter for engineering blood vessel culture described in accordance with the claim 1 monitors system, feature exists In:Two glass pipes being provided symmetrically on the glass wall of glass reactor.
6. monitoring system according to a set of mechanics parameter for engineering blood vessel culture described in claim 4, feature exists In:Changing liquid pipe has one, and permeability cell has two.
7. a set of mechanics parameter for engineering blood vessel culture described in accordance with the claim 1 monitors system, feature exists In:First segment silicone tube, second segment silicone tube, third section silicone tube are integrated.
CN201721470909.9U 2017-11-07 2017-11-07 A set of mechanics parameter for engineering blood vessel culture monitors system Active CN207502096U (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111603611A (en) * 2020-03-06 2020-09-01 广东省人民医院(广东省医学科学院) Cell-derived matrix tubular scaffold and preparation method thereof
CN111855142A (en) * 2020-07-24 2020-10-30 广东省人民医院 Dynamic mechanical response testing system for blood vessels

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111603611A (en) * 2020-03-06 2020-09-01 广东省人民医院(广东省医学科学院) Cell-derived matrix tubular scaffold and preparation method thereof
CN111855142A (en) * 2020-07-24 2020-10-30 广东省人民医院 Dynamic mechanical response testing system for blood vessels

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