CN103948457A - Method for constructing regenerated nerve vascularized bones, cartilages, joints or body surface organs - Google Patents
Method for constructing regenerated nerve vascularized bones, cartilages, joints or body surface organs Download PDFInfo
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Abstract
The invention relates to a method for constructing regenerated nerve vascularized bones, cartilages, joints or body surface organs by a prefabricated female die bracket. Firstly, the female die bracket of a defected tissue or organ is printed in a three-dimension manner by using a computer assisted design/manufacturing technology; then, a surface of a periosteum and/or perichondrium is formed in a body through an operation, the female die bracket is placed and fixedly sutured on a germinal layer of the autologous periosteum and/or perichondrium to form a closed space; after the bones, cartilages, joints or body surface organs whose male die shape corresponds to a female die are regenerated in the space constructed by the female die and the germinal layer of the surface of the periosteum and/or perichondrium, a newly regenerated tissue is taken out, the female die bracket is removed, and the tissue is transplanted to the position of the defected tissue or organ to reconstruct. The newly generated tissue or organ prepared through autologous prefabrication has rich new vessels and nerves, does not contain any exogenous materials participating in tissue regeneration, is high in safety, accurate in shape at the same time, and quite similar to the normal tissue or organ.
Description
Technical field
The present invention relates to medical science and bioengineering field, specifically, relate to a kind of method that builds neural blood vessel bone, cartilage, joint or the body surface organ of regeneration.
Background technology
Tissue, organ defect and dysfunction that the reasons such as various wounds, tumor cause are to cause the main cause of injury of human.And after human tissue organ sustains damage, how making impaired histoorgan structure, function repair and reconstruction is great difficult problems that current biology and clinical medicine interface are faced.Vital tissue, organ damaged all needs to adopt autologous or allosome tissue, organ transplantation to repair conventionally, and there are separately a lot of unavoidable defects in method autologous, heteroplastic transplantation, as autoplastic not enough for source, district, there are immunologic rejection, ethical issues etc. in heteroplastic transplantation.
The concept of organizational project has been proposed the eighties in last century.Proposition thereupon, foundation and development, people have been built with more further investigation to vitro tissue, and for rebuilding and lay a good foundation in body.On the basis of this development, people have started new upsurge to the research of neomorph.And make medical research enter " regenerative medicine epoch ".
In decades, first the external regeneration of organizational project has obtained extensive success, as structure and the reparation of the tissues such as bone, cartilage, skin, trachea, nerve, blood vessel, tendon, cornea have obtained achievement highly visible, and by report and approval widely both at home and abroad.But it exists the much shortcoming that cannot break through in seed cell, biomaterial, the large core realm of the information factor three always, as: cell derived, the body internal contact compatibility that builds tissue, safety, immunologic rejection, moral check etc.And external structure organize ubiquity cannot to build nervus vasculairs problem, these problems all need deep discussion, these problems have also delayed organizational project and regenerative medicine at the step of clinical practice simultaneously.
The appearance of " internal regeneration ", " in-vivo biological reactor " concept, becomes possibility by above-mentioned target." in-vivo biological reactor " is to utilize the self-ability of the organism required organizational structure of regenerating, and is used for repairing corresponding tissue defect.Application " in-vivo biological reactor " can be according to receptor needs, the organizational structure of pre-structure custom-shaped.Owing to being the organ that autologous tissue's regeneration obtains, be transplanted to and be subject to district not have the problems such as immunological rejection.
Warnke gives full play to human potential, take Custom Prosthesis titanium net as profile support, fill hydroxyapatite/rhBMP-7 mixture, utilize the latissimus dorsi m. flesh bag that contains thoracodorsal artery as bioreactor, build vascularization mandible body, be used for repairing Mandible damaged, obtained good result, realized the pre-structure of in-vivo tissue that is transformed into people by zoopery.The people such as Paolo M, successfully repaired left principal bronchus narrow, make the functional reparation of air flue, experimenter is seeded in autologous strong side tracheal epithelial cell on acellular trachea bracket, recycle external " liquid phase " bioreactor and cultivate in vitro 96 hours, after cell and support are fully adhered to, the complex of cell and support is implanted in to the region of tracheal stenosis, postoperative graft survives well, and has obtained good functional restoration.The people such as Chang H Lee, utilize internal milieu completely, by the effect of going back to the nest of cell, the damaged structure of autogenous repairing joint component, author utilizes three-D CT imaging and rapid shaping technique to manufacture the rabbit upper end of humerus shoulder joint defect model of Custom Prosthesis TCP material, on its timbering material, be placed to cartilage growth factor TGF-β 3, its complex kind is implanted in corresponding joint defect model, after 6 months, material is in vivo under the migration and the repair of self of cell, formed corresponding articular surface cartilage structure, function of joint is recovered gradually.
Successful report based on above forefathers, scholars utilize the organizational structure of human body self as bioreactor, have realized the theory from volume reconstruction regeneration goal object.These breakthrough achievements, for building nervus vasculairs bone, trachea, articular cartilage, have all embodied the great potential of internal regeneration.Yet on the one hand, these methods are not still avoided the participations such as Process of in vitro, the exogenous growth factor, allogenic gene completely.And after regenerating tissues is implanted, exogenous cell, material, somatomedin etc. very easily cause the complication such as rejection, infection, cyst form, material can not degrade, expose, this safety issue never solves completely, has seriously restricted the nervus vasculairs bone, trachea, articular cartilage etc. of above structure in clinical application.On the other hand, at present constructed tissue is difficult to neural blood vessel, thus its degenerate after implanting, cannot be further and autologous fusion growth etc. problem, still can not meet the requirement of its defect repair and reconstruction.The 3rd, joint or other organs are to be formed by Various Tissues structure composite, and simple a kind of tissue morphology of external structure is the requirement that cannot meet body far away.The 4th, damage and the disappearance of tissue or organ are diversified, and we need to, by accurately design, realize personalized demand.
In sum, for promoting tissue and organ defect or handicapped reparation, especially promote it in clinical direct application, improve operation satisfaction, need a kind of method that relies on construct in vitro acquisition neural blood vessel tissue or organ without exogenous material participation, shape accurately, completely that builds badly.
Summary of the invention
The object of the invention is for deficiency of the prior art, provide the tissue/organ of utilizing with damaged/disappearance to be the support of former shape, build the method for bone, cartilage, joint or the body surface organ of neural blood vessel.
One object more of the present invention is that a kind of bone, cartilage, joint or body surface organ of neural blood vessel of regeneration is provided.
Another object of the present invention is, the purposes of bone, cartilage, joint or body surface organ of the neural blood vessel of described regeneration is provided.
For achieving the above object, the technical scheme that the present invention takes is:
Utilize with the tissue/organ of damaged/disappearance and be the support of former shape, build the method for bone, cartilage, joint or the body surface organ of neural blood vessel, comprise the following steps:
A) obtain the former support of bone, cartilage, joint or the body surface organ of wish structure;
B) by performing the operation, in body, prepare a complete periosteum and/or cartilage face, on periosteum and/or perichondrium stratum germinativum by the former stentplacement of step a) in body, the fixing former bracket edge of sewing up, makes it form a closed space;
C) otch forming in closed step b) operation process, until described periosteum and/or perichondrium face stratum germinativum side, bear again after bone, cartilage, joint or the body surface organ of the formpiston shape corresponding with former support the bone of complete taking-up neural blood vessel, cartilage, joint or body surface organ.
" obtaining the former support of bone, cartilage, joint or the body surface organ of prebuild " described in step a) specifically: utilize computer-aided design or manufacturing technology, damaged tissue or medical imaging's scan-data are carried out to three-dimensional reconstruction, build defect tissue morphology, according to the data of rebuilding, by three-dimensional printing technology, make defective tissue former again.
" by performing the operation, in body, preparing a complete periosteum and/or cartilage face " described in step b) specifically: directly over rib and/or cartilage, successively cut skin, subcutaneous, Musclar layer; and cut along rib costal cartilage periosteum midline; carefully peel off periosteum and perichondrium; in conjunction with former support size, take out suitable rib and/or cartilage; whole process is carefully protected periosteum and/or perichondral stratum germinativum; connect and sew up adjacent bone film and/or perichondrium again, it is flattened and form a complete periosteum and/or cartilage face.
In step b), the design surface of described former support is placed towards periosteum and/or perichondrium stratum germinativum.
" body " described in step b) is animal body, and described animal can be people, pig, rabbit, Canis familiaris L., rat, mice etc.
For realizing above-mentioned second object, the technical scheme that the present invention takes is:
The bone of the neural blood vessel of regeneration, cartilage, joint or a body surface organ, the bone of the neural blood vessel of described regeneration, cartilage, joint or body surface organ consist of bone and/or cartilage.
The bone of the neural blood vessel of described regeneration, cartilage, joint or body surface organ shape are just in time complementary mutually with former support.
The bone of the neural blood vessel of described regeneration, cartilage, joint or body surface organ are joint, skull, nasal bone or the credulous bone of the neural blood vessel of regeneration.
For realizing above-mentioned the 3rd object, the technical scheme that the present invention takes is:
As above the purposes of bone, cartilage, joint or the body surface organ of the neural blood vessel of arbitrary described regeneration, for the preparation of tissue or the organ of repair deficiency or disappearance.
As used herein, described " bone of the neural blood vessel of regeneration, cartilage, joint or body surface organ " can also be divided into according to its organization type the complex tissue three types of simple bone, simple cartilage and bone and cartilage.
As used herein, described " bone and/or cartilage " is the complex tissue of phalanges, cartilage or bone and cartilage, described " complex tissue of bone and cartilage " is preferably the tissue that bone and cartilage are incorporated into one, and this tissue comprises bone, cartilage, and the transitional region of bone and cartilage.Nose, joint etc. all belong to " complex tissue of bone and cartilage " category.
As used herein, described " former " refers to a kind of mould, and the concaveconvex shape feature of this mould one side and normal structure or the obverse concaveconvex shape feature of organ are coincide mutually.Described former support can be the materials such as hydroxyapatite, silica gel, as long as can be made into defective tissue former shape, and the moulding effect while playing tissue regeneration in implantable.
As used herein, described " design surface of former support " refers to that former support is for allowing the side of complex tissue apposition growth of area of new bone, cartilage or bone and cartilage, and the shape of this face is the shape design of the bone, cartilage, joint or the body surface organ that build according to wish.
As used herein, described " periosteum and/or cartilage face " refers to periosteum face, cartilage face or periosteum face and cartilage face and the transition region of the two.
In the present invention, the junction point between described " joint " phalanges and bone (as femur and hipbone), as articulations digitorum manus, knee joint, even local joint is damaged; Described " body surface organ " comprises the organs such as ear, nose, articulations digitorum manus.
In the present invention, while building the bone, cartilage, joint of the neural blood vessel of regeneration or body surface organ, as bone, cartilage, joint or the body surface organ of the neural blood vessel of regeneration, it is in the nature simple bone, described former is propped up to the stratum germinativum that is placed on periosteum; As bone, cartilage, joint or the body surface organ of the neural blood vessel of regeneration, it is in the nature simple cartilage, described former is propped up and is placed on perichondral stratum germinativum; As bone, cartilage, joint or the body surface organ of the neural blood vessel of regeneration, it is in the nature the complex tissue of bone and cartilage, described former is propped up to the stratum germinativum that is placed on periosteum and perichondrium and the two intersection.
The invention has the advantages that:
The present invention inquires into and has set up a kind of internal milieu of utilizing completely, builds the tissue of personalized customization type neural blood vessel or the method for organ, thereby is used for repair and reconstruction tissue and organ defect, is especially used for repair and reconstruction autologous tissue and corresponding organ damaged.As patient, provide safe, effective, the most lasting therapeutic scheme, and can become the solid foundation of wide clinical application.
Particularly, the present invention utilizes computer-aided design/manufacturing technology (CAD/CAM), and damaged tissue or medical imaging's scan-data are carried out to three-dimensional reconstruction, builds defect tissue morphology.According to the data of rebuilding, by three-dimensional printing technology, make defective tissue former support.Utilize periosteum/perichondrium and nervus vasculairs Shu Zuowei thereof " internal regeneration source ", by personalized former stentplacement most important structure of skeletonization/one-tenth cartilage in body---periosteum/perichondrium (former crowning is towards periosteum/perichondrium stratum germinativum), and fixedly suture material edge in periosteum/perichondrium.A formed closed space is for damaged tissue or the organ of autologous structure.The neural blood vessel tissue that this mode builds and organ (as ear, nose etc.) have the following advantages: what 1. make is the former support of defective tissue or organ, former support is inserted after body, can directly obtain with required tissue or organ shape is in full accord and do not comprise regenerating tissues or the organ of timbering material, in prior art, use formpiston material and/or cultured cell in vitro and somatomedin jointly to insert body, the way that tissue or organ are regenerated thereon, safer, shape is more accurate; 2. utilize the potential of autoregeneration to build damaged purposiveness tissue or organ completely, in whole pre-llex cornuta/regenerating bone or cartilage process, without participations such as cell in vitro incubation, the exogenous growth factor, allogenic genes, thereby guarantee the safety of the pre-structure of in-vivo tissue, overcome that exogenous cell, material, somatomedin etc. implant and the defect of the complication such as the later stage rejection that exists, infection, cyst form, material can not degrade, expose, therefore can directly apply to clinical; 3. final obtained regenerating tissues or organ are entirely bone and/or cartilage, do not contain any timbering material, in timbering material tissue regeneration process in vivo, only play the moulding effect that helps, but not participate in regeneration, in secondary operation, timbering material can be taken out, can not leave over the complication such as the later stage infection that causes in body, rejection because of it; 4. the mobilized to the fullest extent important elements-periosteum/perichondrium of body internal skeleton/Chondrogenesis, periosteum/perichondrium the stratum germinativum that is chosen in rib/costicartilage is inserted former support, the tissue of regeneration or organ have periosteum/perichondrium to cover, it has the clear and definite nervus vasculairs base of a fruit, not only can guarantee the neural blood vessel of pre-structure tissue or organ, also provide and can supply identical nervus vasculairs, for tissue transplantation, reparation are for the damaged sufficient condition that provides in district simultaneously.And the formed natural syndeton of periosteum perichondrium, for the transitional structure in the formed joint of osteochondro tissue provides essential condition; 5. through the former support of CAD/CAM fabrication techniques, organize in vivo and in pre-structure process, played accurate moulding effect, the bone/cartilage tissue of regeneration is without again carving, greatly reduce the requirement to operative doctor, shortened operating time, reduce wound, and avoided existing diversity in normal structure or organ and the artificial tissue of carving or organ shape.
Accompanying drawing explanation
Fig. 1. according to CT three-dimensional reconstruction data and computer-aided design/manufacture (CAD/CAM) technology, rebuild personalized Ipsilateral ear.
Fig. 2. according to data reconstruction, by 3D printing technique, make normal Ipsilateral ear resin mould.
Fig. 3. hydroxyapatite material (HA) perfusion ear shape support, obtains its former.
Fig. 4. press A design in figure, the 6th, 7,8 costicartilages are taken out, carefully protect periosteum and perichondral stratum germinativum.As shown in B in figure, sew up adjacent perichondrium, make it form a complete perichondrium.As shown in C in figure, preprepared former crowning is sewed up to perichondrium stratum germinativum, make it form a closed lacuna, for cartilage tissue regeneration.
Fig. 5. pre-structure tissue was carried out to iconography monitoring in postoperative the 3rd month, visible pre-structure cartilaginous tissue has definite iconography imaging.
Fig. 6. the ear shape cartilaginous tissue profile of pre-structure is accurately clear.
Fig. 7. with the cartilaginous tissue of the pre-structure of the complete taking-up of perichondrium, further prune regeneration of cartilage a small amount of soft tissue around.
Fig. 8. to pruning unnecessary regeneration of cartilage cartilaginous tissue, carry out the blue dyeing of quinovatine, result shows classical cartilage lacuna, cartilage matrix.The visible typical cartilage matrix of II Collagen Type VI immunohistochemical staining.
Fig. 9. the elastic modelling quantity of pre-structure cartilage in the body of embodiment 1.
Figure 10. the maximum deflection load of pre-structure cartilage in the body of embodiment 1.
Figure 11. according to defect of skull, utilize (CAD/CAM) technology, accurately the resin mould of personalized 3 D-printing defective bone tissue.
Figure 12. according to resin mould, make HA former, for pre-structure defective bone tissue.
Figure 13. according to the size of former, in the 6th, 7,8 root bone Position Design, go out corresponding rib periosteum area and the corresponding rib position of the osseous tissue needs of pre-structure.
Figure 14. the rib of the corresponding former size of the 6th, 7,8 rib is taken out, and whole process is carefully protected the stratum germinativum of periosteum.Launch and connect to sew up adjacent bone film, it is paved and form a complete periosteum face (left side).By preprepared former, design surface is placed towards perichondrium stratum germinativum, edge sew up and be fixed on periosteum (in), make a closed lacuna of itself and periosteum formation, for osteanagenesis (right side).
Figure 15. in postoperative the 3rd month, pre-structure tissue is carried out to iconography monitoring, visible pre-structure tissue has definite iconography osteanagenesis evidence.
Figure 16. with the osseous tissue (as needs, can carry nervus vasculairs Shu Gongtong and take out for transplanting) of the pre-structure of the complete taking-up of periosteum simultaneously.
Visible typical bone trabecula medullary cavity and osteoblast under Figure 17 .VG dyeing mirror, rich blood vessel in pulp cavity.
Figure 18. three-color process dyeing, the visible typical bone trabecula spline structure of OC immunohistochemical staining, abundant blood vessel is covered with medullary cavity.
Figure 19. Follow-up After is shown in for 1 year, the obviously absorption of pre-llex cornuta tissue nothing.Facial shape is good.
Figure 20. osseous tissue VG(A), the visible typical bone trabecula medullary cavity of three-color process dyeing (B) and osteoblast, rich blood vessel in pulp cavity.The visible typical bone trabecula spline structure of OC immunohistochemical staining (D); The blue dyeing of quinovatine, the visible typical chondrocyte of col II immunohistochemical staining (E) and abundant endochylema structure.The transition structure of the visible osteochondro tissue of the fast green dyeing of toluidine blue (C).
The specific embodiment
Below in conjunction with accompanying drawing, the specific embodiment provided by the invention is elaborated.
the embodiment 1 pre-structure of body internal ear shape cartilage and reconstruction external ear
Its concrete grammar is achieved through the following technical solutions:
(1) according to organize organ defect, utilize (CAD/CAM) technology accurately personalized 3 D-printing need to build and organizes shape
For personalized microtia patient row ear is reproduced, the Rhizoma Atractylodis Macrocephalae wardrobe portion CT scan of advancing.By CT data with DICOM (Digital Imaging and Communications in Medicine) formatted output, by Medgraphics software and Magic.RP (Magic Rapid Prototyping) software, carry out three-dimensional modeling processing, obtain the threedimensional model (Fig. 1) of ear.Adopt mirror image technology, according to the shape of normally picking up the ears, Ipsilateral ear is carried out to three-dimensional simulation reconstruction process, obtain the threedimensional model of Ipsilateral normal ear, then by the making of stereolithography (Stereolithography, SLA) rapid prototyping, obtain the resin mould (Fig. 2) of Ipsilateral normal ear.The auricle tissue of considering scan rebuilding has comprised soft tissue covering, therefore clear through skin covering rear profile in order to reproduce ear, therefore the SLA model that this research adopts is that the precision architecture of auricle CT data is deepened to 1.16 times of making, has reserved and made up the postoperative ear's subunit fine degree causing because of skin covering and declined.By HA(hydroxyapatite) powder (<40 order) and coagulant according to the weight ratio of 4:6 be in harmonious proportion stir into liquor after resin by injection model get its former (Fig. 3).After autoclave sterilization, independent packaging is standby.
(2) the pre-structure of in-vivo tissue
In self pre-structure process, we mobilize most important structure---perichondrium and nervus vasculairs Shu Zuowei thereof " internal regeneration source ", the personalized auricular cartilage of the accurate shape of completeness autoregeneration that becomes cartilage in body.According to Design (Fig. 4 A), directly over the 7th costicartilage, successively cut skin, subcutaneous, Musclar layer, respectively the costicartilage of the 6th, 7,8 corresponding former sizes to be taken out, whole process is the perichondral stratum germinativum of protection carefully.Connect and sew up adjacent perichondrium, it is flattened and form a complete cartilage face (Fig. 4 B).Preprepared former crowning is placed towards perichondrium stratum germinativum, and edge is sewed up and is fixed in perichondrium, makes itself and perichondrium form a closed space, for cartilage tissue regeneration (Fig. 4 C).The cartilage of taking-up is placed in subcutaneous, and places drain, successively tissue apposition.
(3) regeneration ear shape cartilaginous tissue reproduces for ear
Pre-structure tissue was carried out to iconography monitoring in 1,3 month after surgery respectively, row secondary operation (Fig. 5) after pre-structure tissue has definite iconography evidence.In art, along former otch, successively cut skin, preset HA material is carefully taken out.The ear shape cartilaginous tissue profile of seeing pre-structure is clear (Fig. 6) accurately.Ear shape cartilaginous tissue (as needs, can carry nervus vasculairs Shu Gongtong simultaneously and take out transplanting) with the pre-structure of the complete taking-up of perichondrium.Also receive and be embedded in subcutaneous costicartilage, drainage from indwelling.Skin suture.Further prune regeneration of cartilage a small amount of soft tissue (Fig. 7) around.
The capable histology of pre-structure cartilage under pruning and biomechanics are detected:
1) histology: the regenerating cartilage tissue pruning away is on a small quantity soaked to fixing (the PBS configuration of PH=7.0 ~ 7.5 forms) with 4% paraformaldehyde, and 4 ℃ of preservations, changed once totally 3 days every 12 hours.PBS rinses, the dehydration of ethanol gradient.Tissue slice (5-10 μ m) is carried out in routine paraffin wax embedding.Parallel HE, A Lixinlan, SABC COL II(II collagen type) dyeing.In the newly-generated chondrocyte of optical microphotograph Microscopic observation, endochylema form.
Result shows: A Lixinlan, SABC COL II(II collagen type) the visible typical cartilage lacuna spline structure of dyeing, endochylema enriches (Fig. 8).
2) biological mechanics determining: get the remaining cartilage samples of pre-structure ,-20 ℃ are freezing, before test, under room temperature condition, PBS immersion is steeped, and Material Testing Machine is measured the vertical maximum compression load of cartilage and elastic modelling quantity etc.And select normal costicartilage as a control group.
Result shows: the cartilage of pre-structure in the time of three months after surgery, have the elastic modelling quantity similar to normal costicartilage (for normal rib 90.5 ± 3.9%) (Fig. 9) and maximum compression load (normal rib 86.4 ± 4.9%) (Figure 10), show between the elastic modelling quantity of regenerating tissues and normal cartilage without obvious significant difference.
(4) ear reconstruction
After the ear shape cartilaginous tissue of pre-structure is further pruned, the second stage of row ear reconstruction.According to the otch of Design, process ear skin and the external auditory meatus form of pre-structure, implant pre-structure ear shape cartilaginous tissue.Cover and skin suture drainage from indwelling.Wrapping is fixing.Postoperative 7 days dermal sutures outs.Row cranioauricular angle plasty after 3 months.Respectively at postoperative the 1st, 3,6 with follow up a case by regular visits to for 12 months, row imaging examination, observes cartilaginous tissue and survives situation.
Follow-up After result shows: the visible pre-structure cartilaginous tissue of implanting of CT survives well, and Follow-up After is shown in for 1 year, and structure cartilaginous tissue is without obvious absorption in advance.Ear's outline shape is good.
the embodiment pre-structure of 2 body internal skeleton and reconstruction defect of skull
Its concrete grammar is achieved through the following technical solutions:
(1) according to defect of skull, utilize (CAD/CAM) technology, accurately personalized 3 D-printing need to build organizes shape
For the damaged patient's row of personalized bone is rebuild, in preoperative to patient's bone damaged/maleformation carries out CT scan.By CT data with DICOM (Digital Imaging and Communications in Medicine) formatted output, by Medgraphics software and Magic.RP (Magic Rapid Prototyping) software, carry out three-dimensional modeling processing, obtain the threedimensional model of bone.According to normal side osseous tissue shape, adopt mirror image technology, to Ipsilateral bone, damaged place carries out three-dimensional simulation reconstruction process, obtain affected part normal bone form threedimensional model, then by stereolithography (Stereolithography, SLA) making of rapid prototyping, obtains the resin mould (Figure 11) of defective bone tissue.The osseous tissue of considering scan rebuilding has comprised soft tissue covering, therefore clear in order to rebuild rear profile, therefore the SLA model that this research adopts is that the precision architecture of damaged/lopsided CT data of bone is deepened to 1.16 times of making, has reserved and made up the postoperative local subunit fine degree causing because of skin covering and declined.By HA(hydroxyapatite) powder (<40 order) and coagulant according to the weight ratio of 4:6 be in harmonious proportion stir into liquor after resin by injection model get its former.Independent packaging standby (Figure 12) after autoclave sterilization.And according to the size of former, calculate the area of the periosteum needing.
Meanwhile, to patient's row thorax three-D CT scanning, and carry out three-dimensional reconstruction.Utilize Minics 10 software rebuilds to go out thorax structure.According to the size of former, in 6th ~ 8 root bone Position Design, go out corresponding rib periosteum area and the corresponding rib position of the osseous tissue needs of pre-structure.
(2) the pre-structure of in-vivo tissue
According to Design (Figure 13), directly over the 7th costicartilage, successively cut skin, subcutaneous, Musclar layer, respectively the rib of the corresponding former size of 6th ~ 8 rib to be taken out, whole process is carefully protected the stratum germinativum of periosteum.Launch and connect to sew up adjacent bone film, it is paved and form a complete periosteum face.Preprepared former design surface is placed towards periosteum stratum germinativum, and edge is sewed up and is fixed on periosteum, makes itself and periosteum form a closed space, for osteanagenesis (Figure 14).
(3) pre-llex cornuta tissue obtains
Pre-structure tissue was carried out to iconography monitoring in 1,3 month after surgery respectively, row secondary operation (Figure 15) after pre-structure tissue has definite iconography osteanagenesis evidence.In art, along former otch, successively cut skin, preset HA material is carefully taken out.See that pre-llex cornuta organizes profile accurately clear.With the osseous tissue of the pre-structure of the complete taking-up of periosteum (as needs, can carry nervus vasculairs Shu Gongtong and take out for transplanting) simultaneously (Figure 16).In art, guarantee the integrity of pleura and peritoneum.Also receive and be embedded in subcutaneous rib, drainage from indwelling.Suture muscles, subcutaneous tissue and skin layer.Further prune Regenerated Bone around a small amount of soft tissue and unnecessary pre-llex cornuta tissue.
The capable histology of pre-llex cornuta who prunes and biomechanics are detected:
1) histology: the Regenerated Bone tissue pruning away is on a small quantity soaked to fixing (the PBS configuration of pH=7.0 ~ 7.4 forms) with 4% paraformaldehyde, and 4 ℃ of preservations, changed once totally 3 days every 12 hours.PBS rinses, EDTA(10%) slowly decalcification.Within three days, change decalcifying Fluid once.After decalcification completely, PBS rinses, the dehydration of ethanol gradient.Tissue slice (5-10 μ m) is carried out in routine paraffin wax embedding.Parallel HE, VG, green, three-color process dyeing soon, SABC OC(osteocalcin) dyeing.In form and the revascularization situation of the newly-generated osteocyte of optical microphotograph Microscopic observation, bone trabecula, medullary cavity.
Result shows: visible typical bone trabecula medullary cavity and osteoblast under VG dyeing mirror, rich blood vessel in pulp cavity.Three-color process dyeing, the visible typical bone trabecula spline structure of OC immunohistochemical staining, abundant blood vessel structure are covered with medullary cavity (Figure 17,18).
2) biological mechanics determining: get the remaining bone specimen of pre-structure ,-20 ℃ freezing, before test, under room temperature condition, PBS immersion bubble, measures cartilage maximum compression load and elastic modelling quantity etc.And select normal rib as a control group.
Result shows: the skull of pre-structure in the time of three months after surgery, have the elastic modelling quantity similar to normal rib (for normal rib 88 ± 5.6%) and maximum compression load (normally 108 ± 3.4% of rib).The obvious significant difference of nothing between the elastic modelling quantity of demonstration regenerating tissues and normal bone.
(4) repair of cranial defects is rebuild orthopedic procedure
The pre-llex cornuta tissue taking out is implanted to defect of skull position, the second stage of repair of cranial defects Reconstruction of row.Particularly: the pre-llex cornuta of having pruned is organized to implantable bone defect.Skin suture, wrapping is fixing.Postoperative 7 days dermal sutures outs.Respectively at the 1st, 3,6 with follow up a case by regular visits to for 12 months, row imaging examination, observes osseous tissue and survives and bone fusion phenomenon.
Follow-up After result shows: the visible pre-llex cornuta tissue of implanting of CT survives well, with upper jaw bone fusion growth.Follow-up After is shown in for 1 year, the obviously absorption of pre-llex cornuta tissue nothing, and facial shape is good, and profile obviously improves.(Figure 19).
the pre-structure of nose shape bone/cartilage and reconstruction nasal bone in embodiment 3 bodies
Its concrete grammar is achieved through the following technical solutions:
(1) damaged according to bone, utilize (CAD/CAM) technology, accurately personalized 3 D-printing need to build and organize shape
For the damaged patient's row of personalized bone is rebuild, in preoperative, patient's head is carried out to CT scan.By CT data with DICOM (Digital Imaging and Communications in Medicine) formatted output, by Medgraphics software and Magic.RP (Magic Rapid Prototyping) software, carry out three-dimensional modeling processing, obtain the threedimensional model of head soft tissue.According to normal header, organize shape, defect of nose place is carried out to three-dimensional simulation reconstruction process, obtain the nose form of mating with face contour.And further link up with patient, understand the requirement of patient to postoperative nose profile, reach consistent rear row reconstruction of nose.
According to the nose outline shape of three-dimensional simulation, 3 D-printing goes out the nose skeleton pattern that patient is desirable, then by the making of stereolithography (Stereolithography, SLA) rapid prototyping, obtains the profile resin mould of damaged nasal tissue.The osseous tissue of considering scan rebuilding has comprised soft tissue covering, therefore clear in order to rebuild rear profile, therefore the SLA model that this research adopts is that the precision architecture of the wide soft tissue data of nosewheel is increased to 1.2 times of making, reserve and made up the decline of the postoperative local subunit fine degree causing because of skin covering.By HA(hydroxyapatite) powder (<40 order) and coagulant according to the weight ratio of 4:6 be in harmonious proportion stir into liquor after resin by injection model get its former.After autoclave sterilization, independent packaging is standby.
Meanwhile, to patient's row thorax three-D CT scanning, and carry out three-dimensional reconstruction.Utilize Minics 10 software rebuilds to go out thorax structure.According to the size of former, in the 6th, the 7 root position of bone, put, according to the size of former, calculate the exact position of periosteum and perichondral area and the pre-structure tissue of needs.
(2) the pre-structure of in-vivo tissue
According to Design, directly over the 6th, 7 costochondral junction places, successively cut skin, subcutaneous, Musclar layer, respectively the rib of the corresponding former size of the 6th, 7 rib and costicartilage to be taken out, whole process is carefully protected periosteum and perichondral stratum germinativum.Launch and connect to sew up adjacent periosteum and perichondrium, it is paved and form a complete periosteum and cartilage face.Preprepared former design surface is placed towards periosteum and perichondrium stratum germinativum, and edge is sewed up and is fixed in periosteum and perichondrium, makes itself and periosteum and perichondrium form a closed space, for bone and cartilage tissue regeneration.The cartilage of taking-up is placed in subcutaneous, and places drain, successively tissue apposition.
(3) reparation in regenerating tissues Dui Gong district and reconstruction
Within 1,3 month after surgery, pre-structure tissue is carried out to iconography monitoring, row secondary operation after pre-structure tissue has definite iconography bone and cartilage tissue regeneration evidence respectively.In art, along former otch, successively cut skin, preset HA material is carefully taken out.See that pre-llex cornuta and cartilaginous tissue profile are accurately clear.Nose shape bone/cartilage tissue (as needs, can carry nervus vasculairs Shu Gongtong simultaneously and take out, for transplanting) with periosteum and the pre-structure of the complete taking-up of perichondrium.In art, guarantee the integrity of pleura and peritoneum.Also receive and be embedded in subcutaneous rib and costicartilage.Drainage from indwelling.Suture muscles, subcutaneous tissue and skin layer.Further prune Regenerated Bone around a small amount of soft tissue and the unnecessary pre-structure tissue of bone cartilage.
The capable histology of pre-llex cornuta/cartilage under pruning and biomechanics are detected:
1) histology: the Regenerated Bone pruning away on a small quantity and cartilaginous tissue are soaked to fixing (the PBS configuration of PH=7.0 ~ 7.5 forms) with 4% paraformaldehyde, and 4 ℃ of preservations, changed once totally 3 days every 12 hours.PBS rinses, EDTA(10%) slowly decalcification.Within three days, change decalcifying Fluid once.After decalcification completely, PBS rinses, the dehydration of ethanol gradient.Tissue slice (5-10 μ m) is carried out in routine paraffin wax embedding.Parallel HE, VG, green-Toluidine blue staining, SABC OC(osteocalcin soon), COL II dyeing.In the form of the newly-generated osteocyte of optical microphotograph Microscopic observation, bone trabecula, medullary cavity, chondrocyte.
Result shows: visible typical bone trabecula medullary cavity and osteoblast under mirror, rich blood vessel in pulp cavity.The visible typical bone trabecula spline structure of OC immunohistochemical staining; Typical chondrocyte and abundant endochylema structure.The COL II visible cartilage lacuna structure (Figure 20) that dyes.
2) biological mechanics determining: get remaining bone and the cartilage samples of pre-structure ,-20 ℃ freezing, before test, under room temperature condition, PBS immersion bubble, measures respectively the vertical maximum compression load of bone/cartilage and elastic modelling quantity etc.And select normal rib/cartilage as a control group.
Result shows: the bone/cartilage of pre-structure in the time of three months after surgery, have the elastic modelling quantity similar to normal rib and costicartilage (for normal costicartilage 81.3 ± 6.4%) and maximum compression load (normally 108.7 ± 5.7 % of rib).The obvious significant difference of nothing between the elastic modelling quantity of demonstration regenerating tissues and normal bone/cartilage.
(4) defect of nose is rebuild redressment
After the nose shape bone/cartilage tissue of pre-structure is further pruned, the second stage of reconstruction of nose of row.According to the otch of Design, process skin of nose and the lining of pre-structure, in bridge of the nose portion, implant pre-structure nose shape bone/cartilage tissue.Edge is fixed on upper jaw bone relevant position.Cover and skin suture, assurance bridge of the nose skin and intranasal lining are organized the nose type tissue that covers pre-structure completely.Nasal tube supports.Wrapping is fixing.Postoperative 7 days dermal sutures outs.Respectively at postoperative the 1st, 3,6 with follow up a case by regular visits to for 12 months, row imaging examination, observes osseous tissue and survives and bone fusion phenomenon.
Follow-up After result shows: the visible pre-structure bone/cartilage tissue of implanting of CT survives well, with upper jaw bone fusion growth.Follow-up After is shown in for 1 year, and pre-structure bone/cartilage tissue is without obvious absorption.Nose form is good.
The above is only the preferred embodiment of the present invention; it should be pointed out that for those skilled in the art, do not departing under the prerequisite of the inventive method; can also make some improvement and supplement, these improvement and supplement and also should be considered as protection scope of the present invention.
Claims (8)
1. utilize with the tissue/organ of damaged/disappearance and be the support of former shape, build the method for bone, cartilage, joint or the body surface organ of neural blood vessel, it is characterized in that, comprise the following steps:
A) obtain the former support of bone, cartilage, joint or the body surface organ of wish structure;
B) by performing the operation, in body, prepare a complete periosteum and/or cartilage face, on periosteum and/or perichondrium stratum germinativum by the former stentplacement of step a) in body, the fixing former bracket edge of sewing up, makes it form a closed space;
C) otch forming in closed step b) operation process, until described periosteum and/or perichondrium face stratum germinativum side, bear again after bone, cartilage, joint or the body surface organ of the formpiston shape corresponding with former support the bone of complete taking-up neural blood vessel, cartilage, joint or body surface organ.
2. method according to claim 1, it is characterized in that, " obtaining the former support of bone, cartilage, joint or the body surface organ of prebuild " described in step a) specifically: utilize computer-aided design or manufacturing technology, damaged tissue or medical imaging's scan-data are carried out to three-dimensional reconstruction, build defect tissue morphology, according to the data of rebuilding, by three-dimensional printing technology, make defective tissue former again.
3. method according to claim 1, it is characterized in that, " by performing the operation, in body, preparing a complete periosteum and/or cartilage face " described in step b) specifically: directly over rib and/or cartilage, successively cut skin, subcutaneous, Musclar layer, and cut along rib costal cartilage periosteum midline, carefully peel off periosteum and perichondrium, in conjunction with former support size, take out suitable rib and/or cartilage, whole process is carefully protected periosteum and/or perichondral stratum germinativum, connect again and sew up adjacent bone film and/or perichondrium, it is flattened and form a complete periosteum and/or cartilage face.
4. method according to claim 1, is characterized in that, in step b), the design surface of described former support is placed towards periosteum and/or perichondrium stratum germinativum.
5. the bone of the neural blood vessel of regeneration, cartilage, joint or a body surface organ, is characterized in that, the bone of the neural blood vessel of described regeneration, cartilage, joint or body surface organ consist of bone and/or cartilage.
6. the bone of the neural blood vessel of regeneration according to claim 5, cartilage, joint or body surface organ, is characterized in that, the bone of the neural blood vessel of described regeneration, cartilage, joint or body surface organ shape are just in time complementary mutually with former support.
7. the bone of the neural blood vessel of regeneration according to claim 5, cartilage, joint or body surface organ, it is characterized in that, the bone of the neural blood vessel of described regeneration, cartilage, joint or body surface organ are joint, skull, nasal bone or the credulous bone of the neural blood vessel of regeneration.
8. the purposes of the bone of the neural blood vessel of the arbitrary described regeneration of claim 5-7, cartilage, joint or body surface organ, is characterized in that, for the preparation of tissue or the organ of repair deficiency or disappearance.
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Cited By (5)
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| CN104382670A (en) * | 2014-12-08 | 2015-03-04 | 西安交通大学 | Bionic construction method of artificial organics |
| CN106859848A (en) * | 2017-02-08 | 2017-06-20 | 苏法仁 | A kind of continuous negative pressure drainage device for skin expansion method total auricular reconstruction |
| CN107874872A (en) * | 2017-11-07 | 2018-04-06 | 陕西百普生医疗科技发展有限公司 | A kind of degradable nose dummy of 3D printing |
| CN109893301A (en) * | 2019-04-23 | 2019-06-18 | 上海市第六人民医院 | A kind of transplant and method for repairing articular cartilage defect |
| CN114699559A (en) * | 2022-03-18 | 2022-07-05 | 北京大学第三医院（北京大学第三临床医学院） | Construction method of cartilage scaffold |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104382670A (en) * | 2014-12-08 | 2015-03-04 | 西安交通大学 | Bionic construction method of artificial organics |
| CN104382670B (en) * | 2014-12-08 | 2016-05-04 | 西安交通大学 | A kind of bionical construction method of artificial organs |
| CN106859848A (en) * | 2017-02-08 | 2017-06-20 | 苏法仁 | A kind of continuous negative pressure drainage device for skin expansion method total auricular reconstruction |
| CN106859848B (en) * | 2017-02-08 | 2023-09-12 | 中国人民武装警察部队山东省总队医院 | Continuous negative pressure drainage device for auricle reconstruction by skin expansion method |
| CN107874872A (en) * | 2017-11-07 | 2018-04-06 | 陕西百普生医疗科技发展有限公司 | A kind of degradable nose dummy of 3D printing |
| CN109893301A (en) * | 2019-04-23 | 2019-06-18 | 上海市第六人民医院 | A kind of transplant and method for repairing articular cartilage defect |
| CN114699559A (en) * | 2022-03-18 | 2022-07-05 | 北京大学第三医院（北京大学第三临床医学院） | Construction method of cartilage scaffold |
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