CN107551330A - Tip biomembrane batch making method - Google Patents

Abstract

The present invention provides tip biomembrane batch making method, comprises the following steps：1）Section is made in advance to be star-like, the model that four drift angles are " V " font and drift angle section and fracture line section coincide；2）Model is immersed to the first solution layer, the second solution layer successively, first solution forms elastic layer, for fine and close degradable or nondegradable biomembrane, second solution layer forms medicine layer, medicine layer material be and the good degraded or non-degradable of human body bone bio-compatible, absorb do not absorb either or porosity and looseness material, be also encapsulated with the medicine for having facilitation to sclerotin healing inside medicine layer；3）After air-drying shape fixation etc. biological microstructure film, size as needed is cut the biological microstructure film made along the oval circumference in model section, and the ring-type biomembrane for cutting later is peeled off from model vertex.

Description

Tip biomembrane batch making method

Technical field

Present invention relates to tip biomembrane batch making method.

Background technology

It is attached to currently with the biological composite membrane comprising growth factor/stem cell at fracture line, to strengthen union Speed and quality, it has been the Disciplinary Frontiers of medical research.Fracture line（Concordant profipole）Blood vessel, osteocyte etc. is distributed with inner surface, Whether healing is good, depending on blood vessel, the growing state of osteocyte in fracture anastomosis line.Biomembrane is fitted in fracture anastomosis line Why surface can increase the quality of union, and its reason is the medicine of one side biomembrane encapsulated inside to fracture anastomosis The growth of blood vessel, osteocyte in line has a facilitation, and another aspect biomembrane is by tissue and fracture such as the muscle in the external world Concordant profipole is isolated, and prevents reaction of the tissue to blood vessel, bone cell growth in fracture anastomosis line.Therefore, it is biological Facilitation of the film to union, it should be embodied in and effective medicine and the isolation external world are applied with to fracture anastomosis line inner surface The tissue such as muscle.

The way of contact of existing biological composite membrane and fracture line is often by the way of being directly bonded, but this kind of mode Bring problems with：

1, biological composite membrane bulk area is bigger, and fracture area is smaller, and 2 can not effectively be bonded and be fixed on one Rise.

2, the limitation of current biological composite membrane material and manufacture craft, cause the degradation speed of biological composite membrane, carry Growth factor release active drug concentration time（The valid density duration is the key of fracture line healing quality） It can not be met clinical needs etc. performance indications.See《Growth factor slow-release system promotes the experimental study of fracture of mandible healing》； 《Growth factor/collagem membrane slow-released system promotes the research of union》.

Therefore, on the basis of existing biological composite membrane manufacture craft, new structure of composite membrane, and newly compound are explored The fitting of film and fracture line and fixed form, strengthen the speed and quality of union, into the direction of scientific and technical personnel's innovation.

The content of the invention

Tip biomembrane batch making method, comprises the following steps：

1）Section is made in advance to be star-like, the model that four drift angles are " V " font and drift angle section and fracture line section coincide；

2）Model immerses to the first solution layer, the second solution layer successively, the first solution forms elastic layer, to be fine and close degradable or Nondegradable biomembrane, the second solution layer form medicine layer, and medicine layer material is and the good drop of human body bone bio-compatible Solution is non-degradable, absorb do not absorb either or porosity and looseness material, be also encapsulated with to sclerotin healing inside medicine layer There is the medicine of facilitation；

3）Air-dried etc. biological microstructure film after shape fixes, size as needed is by the biological microstructure film made along mould The oval circumference in type section is cut, and the ring-type biomembrane for cutting later is peeled off from model vertex.Model is made with waxed, Wax and elastic layer material are immiscible from each other, are easy to peel off from wax pattern after air-drying.

Further, fracture line section after in vitro people's bone artificial fracture with being made.The different people in fracture line section It is all similar.Therefore fracture line section after in vitro people's bone artificial fracture with being made.

Further, drift angle section is " V " font and the model identical with fracture line section is cast on fracture line with wax, Then wax solidification is waited to be formed model later.Wax and sclerotin are also immiscible, drift angle section be " V " font and with fracture line section Identical model is cast on fracture line with wax, then waits wax solidification to be formed model later, the model is easy to from fracture Taken off on line.

Further, biological microstructure film periphery is can not permeate the medical bio of the stimulate neuronal growth factor and stem cell Glue is closed.

Further, the elastic layer material is in PLA, collagen, fibrin, biogel, poly butyric ester One or several kinds of mixtures.

Further, the elastic layer material is that can not permeate the medical bio of the stimulate neuronal growth factor and stem cell Glue.

Further, medicine Rotating fields are and human body bone bio-compatible good fiber shape or areolation.

Further, the material of medicine layer is using the material for having facilitation after degraded to bone cell growth.

Further, medicine layer material is that either cellulose or biogel or sterilization or disappear at algal gel azelon Cytotoxic activity charcoal.

Further, the combination of growth factor either stem cell or growth factor and stem cell is encapsulated with medicine layer.

Further, medicine layer is encapsulated with degradable medicaments slow-released system.

On the structure and material inside each layer of biomembrane, in biomembrane related paper and patent document, discuss That states is perfectly clear, such as 201510716279.8 a kind of composite repairing materials for being used to bridge defect nerve and its support, 201480055424.6 compositions and delivery system, 201280027492.2 are for regenerative medicine and for tissue supports Bio-compatible and biodegradable gradient layer system.Section is V-shaped after the application is characterised by its folding.Respectively Structure and material inside layer, can under the requirement for carrying medicine and delivery system for meeting to be bonded together in the form of biological composite membrane With from the various structures and material provided in above paper and patent document.

Due to the limitation of biomembrane manufacture craft, the biomembrane one side volume of whole is larger, on the other hand real and bone The area for rolling over the contact of concordant profipole inner surface depends on the area of fracture anastomosis line inner surface.So only and fracture anastomosis line in table Medicine on the biomembrane in that block region of face contact can just contact fracture anastomosis line inner surface.Therefore, the application really needs The technical problem of solution is：

First, how in biomembrane manufacture craft（Each Rotating fields and material）On the Process ba- sis not improved further, fracturing In the case that concordant profipole inner surface area is constant, the concentration of increase biomembrane release medicine and time；

Second, how preferably biomembrane to be bonded and is fixed on fracture anastomosis line；

Third, how preferably the tissues such as the muscle in the external world and fracture anastomosis line inner surface to be mutually isolated.

For first problem, after fracture operation, fracture anastomosis line（Between between the knochenbruch surface being stitched together Gap）Formation cross-section is " V " type trench structure.If being directly bonded horizontal biomembrane on the trench structure, now give birth to Thing film and the area of fracture anastomosis line inner surface contact are only：The length of the width * trench structures of " V " type trench structure upper surface Degree.If the biomembrane that section itself is also " V " type is filled in the trench structure inner surface, now biomembrane and fracture The area of concordant profipole inner surface contact is at least：The length * 2 of the depth * trench structures of " V " type trench structure.In ' V ' type groove type When the depth of the width of structure upper surface " and ' V ' type trench structure " ratio is close to " 1 ", now obvious 2nd kind of biofilm structure Can be in biomembrane manufacture craft（Each Rotating fields and material）On the Process ba- sis not improved further, in fracture anastomosis line In the case that surface area is constant, increase biomembrane and the area of fracture anastomosis line inner surface contact.

For Second Problem, later composite biological film is folded, because its internal layer is elastic layer, outer layer is weaker zone （Medicine layer）, therefore later " V " type structure is folded, by the elastic reaction of internal layer elastic layer（Elastic layer material is fine and close, folds Restoring force is produced later）, itself has the trend expanded to both sides.Elastic force caused by certain elastic layer is very little, still But it is enough interior table of the edge " compression " at left and right sides of the top composite biological film " V " type structure in fracture anastomosis line both sides Face.

For the 3rd problem, principle is same as above, because the edge " compression " at left and right sides of composite biological film top is being fractured The inner surface of concordant profipole both sides, hence in so that the tissue such as fracture anastomosis line inner surface and outside muscle obtain effectively every From.

Simultaneously as the elastic layer material is that can not permeate the Medical Living Creature Gum of growth factor, therefore medicine layer is encapsulated Medicine, can only be to inner side（Fracture anastomosis line inner surface）Release, can not discharge laterally（The human body tissue sides such as muscle）So that Limited entrapped drug（One of biomembrane process bottleneck is exactly the amount of entrapped drug can not be too many）Can be with targeted release to fracture Concordant profipole inner surface, reach the purpose precisely treated.

What is required emphasis is a little that the application uses outer layer as weaker zone（Medicine layer）It is direct with fracture anastomosis line inner surface The mode of contact, brings a performance more superior than traditional biological film laminating type, i.e. weaker zone can draw in bony surface Lead osteocyte to grow in the material of porosity and looseness, new osteocyte can also obtain entrapped drug in weaker zone in production process Effective nourishing and promotion.As for porosity and looseness material in itself, degradable substance can be selected to make, or even further, Made using the material for having facilitation after degraded to bone cell growth.

What is retrieved when the application submits heals applied to fracture anastomosis line closest to for documents, not retrieving Foldable structure composite biological film.Expand application field to be retrieved, CN201510716279.8 is due to proposing compound bio Film using when first pass through folding or convolution formed fibroin layer be internal layer, collagen layer is middle level, high polymer layer is outer layer Bridge grafting nerves support, belong to application field difference, but disclose more technical characteristic.But it does not still destroy the application Creativeness.It can be found from CN201510716279.8 accompanying drawing 3, the purpose for playing folding and convolution is by composite biological film Formed " concentric multi-layer cylinder structure ", change technical characteristic and the application be different, secondly its solve be " will fold or certificate Support after folding（Multi-layer cylinder structure composite biomembrane）Both ends and the nerve tract both ends blocked are sutured by surgical method " Its technical problem solved, the technique effect and the application of acquirement are entirely different, therefore do not destroy the creativeness of the application.

Brief description of the drawings

Fig. 1 is schematic diagram of the present invention.

Embodiment

With reference to figure 1, tip biomembrane batch making method, comprise the following steps：

1）Section is made in advance to be star-like, the model 1 that four drift angles are " V " font and drift angle section and fracture line section coincide；

2）Model immerses to the first solution layer, the second solution layer successively, the first solution forms elastic layer, to be fine and close degradable or Nondegradable biomembrane, the second solution layer form medicine layer, and medicine layer material is and the good drop of human body bone bio-compatible Solution is non-degradable, absorb do not absorb either or porosity and looseness material, be also encapsulated with to sclerotin healing inside medicine layer There is the medicine of facilitation；

3）Air-dried etc. biological microstructure film after shape fixes, the edge of biological microstructure film 1 that size as needed will be made The oval circumference in model section is cut, and the ring-type biomembrane for cutting later is peeled off from model vertex.

Claims (10)

1. tip biomembrane batch making method, comprises the following steps：

1）Section is made in advance to be star-like, the model that four drift angles are " V " font and drift angle section and fracture line section coincide；

2）Model immerses to the first solution layer, the second solution layer successively, the first solution forms elastic layer, to be fine and close degradable or Nondegradable biomembrane, the second solution layer form medicine layer, and medicine layer material is and the good drop of human body bone bio-compatible Solution is non-degradable, absorb do not absorb either or porosity and looseness material, be also encapsulated with to sclerotin healing inside medicine layer There is the medicine of facilitation；

3）Air-dried etc. biological microstructure film after shape fixes, size as needed is by the biological microstructure film made along mould The oval circumference in type section is cut, and the ring-type biomembrane for cutting later is peeled off from model vertex.

2. tip biomembrane batch making method as claimed in claim 1, it is characterized in that：The in vitro people's bone in fracture line section It is made after artificial fracture.

3. tip biomembrane batch making method as claimed in claim 2, it is characterized in that：Drift angle section be " V " font and and The identical model in fracture line section is cast on fracture line with wax, then waits wax solidification to be formed model later, then by mould Type is taken off from fracture line.

4. tip biomembrane batch making method as claimed in claim 3, it is characterized in that：4）Before, by biological micro-structural Closed so that the Medical Living Creature Gum of the stimulate neuronal growth factor and stem cell can not be permeated on film periphery.

5. tip biomembrane batch making method as claimed in claim 4, it is characterized in that：The elastic layer material is poly- breast One or several kinds of mixtures in acid, collagen, fibrin, biogel, poly butyric ester.

6. tip biomembrane batch making method as claimed in claim 5, it is characterized in that：The elastic layer material is to ooze The Medical Living Creature Gum of saturating the stimulate neuronal growth factor and stem cell.

7. tip biomembrane batch making method as claimed in claim 6, it is characterized in that：Medicine Rotating fields are and human body bone Bio-compatible good fiber shape or areolation.

8. tip biomembrane batch making method as claimed in claim 7, it is characterized in that：The material of medicine layer use degraded with There is the material of facilitation to bone cell growth afterwards.

9. tip biomembrane batch making method as claimed in claim 8, it is characterized in that：Medicine layer material be azelon or Person's cellulose either biogel or sterilization algal gel or antimicrobial activity charcoal.

10. tip biomembrane batch making method as claimed in claim 9, it is characterized in that：Be encapsulated with medicine layer growth because The combination of sub either stem cell or growth factor and stem cell.