CN201510424U - Patch, tissue transplantation supporting frame, tissue regenerative device and structure - Google Patents
Patch, tissue transplantation supporting frame, tissue regenerative device and structure Download PDFInfo
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- CN201510424U CN201510424U CN2009200044822U CN200920004482U CN201510424U CN 201510424 U CN201510424 U CN 201510424U CN 2009200044822 U CN2009200044822 U CN 2009200044822U CN 200920004482 U CN200920004482 U CN 200920004482U CN 201510424 U CN201510424 U CN 201510424U
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Abstract
The utility model relates to a multiple-layer patch, in particular to a tissue transplantation supporting frame and / or device, which comprises an epithelial basement membrane for inducing the repair of mammal tissue coloboma and the in vitro cell expansion of epithelial tissues coming from homothermal vertebrates.
Description
Technical field
This utility model relates to the field of patch, organization bracket or tissue regeneration device.
Background technology
The submucosa tissue of warm-blooded vertebrate in tissue graft material of great use.For example, the tela submucosa transplantation group compound that derives from small intestinal is described in U.S. Patent No. 4,902,508 (' 508 patent hereinafter referred to as) and U.S. Patent No.s 4, in 956,178 (' 178 patents hereinafter referred to as), and the submucosa tissue transplantation group compound that derives from bladder is described in U.S. Patent No. 5, in 554,389 (' 389 patents hereinafter referred to as).All these compositionss are made of homologue's layer basically, and by the same procedure preparation, difference is that initiation material is small intestinal on the one hand and is bladder on the other hand.Describe in detail in ' 178 patent that the process that describes in detail in the patent of ' 508 is incorporated in the patent of ' 389 by reference and this process exists, it comprises that the abrasion step is to remove the internal layer of this tissue, the inner chamber part that comprises the tunica mucosa of small intestinal at least or bladder, be epithelium mucous layer (epithelium) and lamina propria, as in the patent of ' 178, describing in detail.Abrasion, glass or scraping mucosa make the epithelial cell basement membrane relevant with them, and most lamina propria, at least on the level of the closely knit connective tissue layer of organizational structure, compacted zone peel off (layering, delaminate).Therefore, the tissue graft material that before is identified as the soft tissue substitution material does not have basement membranes of epithelium and is made of tela submucosa and compacted zone.
Basement membranes of epithelium is the thin slice of the outer material of born of the same parents of next-door neighbour's epithelial cell substrate.The epithelial thin slice of the gathering of similar type forms epithelium.The inner chamber that the basement membranes of epithelium that epithelial cell is relevant with them is positioned at mucosa is partly gone up and is constituted the tubulose of health and the inner surface of hollow organ and tissue.The basement membranes of epithelium that epithelial cell is relevant with them also is positioned at the outer surface of health, promptly on the skin.Example with typical epithelium of basement membrane includes but not limited to following: the epithelium of skin, intestinal, bladder, esophagus, stomach, cornea regulating liver-QI.
Epithelial cell is positioned on the inner chamber or face side of basement membranes of epithelium, and is relative with connective tissue.Connective tissue for example tela submucosa is positioned at the nearly chamber or the dark side of basement membrane.The example that is positioned at the connective tissue on the nearly chamber side of basement membranes of epithelium is the tela submucosa of intestinal and bladder, and the corium of skin and subcutaneous tissue.
The utility model content
In one aspect, this utility model provides a kind of multilamellar patch, and it comprises one or more composite beds, and each composite bed comprises: lining (1); Isolating inactivation lamina propria (C) on lining (1); And the isolating inactivation basement membranes of epithelium (B) on lamina propria (C), wherein this multilamellar patch is by the compression and/or bonding formation of described composite bed.
In a preferred implementation, described multilamellar patch further comprises isolating inactivation tela submucosa (D), wherein this tela submucosa (D) next-door neighbour's lamina propria (C) below.
In a preferred implementation, described multilamellar patch further comprises isolating inactivation sarolemma (E), wherein this sarolemma (E) next-door neighbour's tela submucosa (D) below.
On the other hand, this utility model provides a kind of and is used to recover, rebuilds, substitutes or multilayer tissue's stent graft of repair tissue, and it comprises one or more composite beds, and each composite bed comprises: lining (1); Isolating inactivation lamina propria (C) on described lining (1); And the isolating inactivation basement membranes of epithelium (B) on described lamina propria (C), wherein multilayer tissue's stent graft is by the compression and/or bonding formation of described composite bed.
In a preferred implementation, described lamina propria (C) separates from dead mammiferous epithelial tissue with basement membranes of epithelium (B), and described basement membranes of epithelium (B) does not have epithelial cell and epithelial cell element.
In a preferred implementation, described compression is undertaken by vacuum compression.
In a preferred implementation, described bondingly undertaken by using-system glue or medical type PUR.
In a preferred implementation, described multilayer tissue stent graft further comprises isolating inactivation tela submucosa (D), and wherein said tela submucosa (D) is close to described lamina propria (C) below.
In a preferred implementation, described multilayer tissue stent graft further comprises isolating inactivation sarolemma (E), and wherein said sarolemma (E) is close to described tela submucosa (D) below.
In a preferred implementation, described tissue transplantation support is thin slice, pipe, ring or coating of particles.
In yet another aspect, this utility model provides a kind of and is used to recover, rebuilds, substitutes or multilayer tissue's stent graft of repair tissue, and it comprises a plurality of composite beds, and each composite bed comprises: lining (1); Isolating inactivation lamina propria (C) on described lining (1); And the isolating inactivation basement membranes of epithelium (B) on described lamina propria (C), wherein said multilayer tissue stent graft forms by compression and/or bonding two, three, four, five or six described composite beds.
In a preferred implementation, described multilayer tissue stent graft further comprises isolating inactivation tela submucosa (D) or isolating inactivation sarolemma (E), or further comprises isolating inactivation tela submucosa (D) and isolating inactivation sarolemma (E).
On the other hand, this utility model provides a kind of tissue transplantation device, comprise: separate lamina propria and mammal basement membranes of epithelium from mammalian epithelial tissue, the epithelial cell of wherein said mammal basement membranes of epithelium and lamina propria and described mammalian epithelial tissue is peeled off.
On the other hand, this utility model provides a kind of tissue transplantation device, comprise: separate tela submucosa and mammal basement membranes of epithelium from mammalian epithelial tissue, the epithelial cell of wherein said mammal basement membranes of epithelium and tela submucosa and described mammalian epithelial tissue is peeled off.
In a preferred implementation, described mammalian epithelial tissue comprises the epithelial tissue from bladder.
In a preferred implementation, described mammalian epithelial tissue comprises the mammalian epithelial tissue from bladder.
On the other hand, this utility model provides a kind of device that is used to induce the mammalian tissues reparation, comprise: isolating inactivation mammal basement membranes of epithelium, wherein said mammal basement membranes of epithelium derive from bladder and do not have epithelial cell and the epithelial cell element; And lamina propria.
On the other hand, this utility model provides a kind of device that is used to recover, substitute or repair urogenital tract tissue, stomach intestinal tissue, skin histology, nervous tissue, cardiovascular organization or connective tissue, comprise: the lamina propria of the described basement membrane of inactivation mammal basement membranes of epithelium and next-door neighbour below, wherein said basement membranes of epithelium does not have epithelial cell and epithelial cell element.
On the other hand, this utility model provides a kind of structure that is used to recover, rebuild or repair described urogenital tract tissue, cardiovascular organization, stomach intestinal tissue, skin histology, nervous tissue or connective tissue, comprising: the inactivation basement membranes of epithelium and the lamina propria of at least a portion of peeling off from mammalian epithelial tissue.
On the other hand, this utility model provides a kind of inactivation structure that is used to induce the mammalian tissues defect repair, comprising: the lamina propria of the described basement membrane of isolating inactivation mammal basement membranes of epithelium and next-door neighbour below, wherein said basement membrane derives from bladder or small intestinal.
On the other hand, this utility model provides a kind of inactivation structure, comprise: (a) lamina propria of the described basement membranes of epithelium of mammal basement membranes of epithelium and next-door neighbour below, the epithelial cell of the epithelium of wherein said basement membrane and lamina propria and mammalian epithelial tissue lamina propria and nearly cavity segment is peeled off; Or (b) smooth muscle cell of mammal basement membranes of epithelium, lamina propria and described sarolemma, the epithelial cell of wherein said basement membrane, lamina propria and smooth muscle and mammal epithelium is peeled off; Or (c) mammal basement membranes of epithelium and tela submucosa, the epithelium of wherein said basement membrane and tela submucosa and mammalian epithelial tissue and the epithelial cell of sarolemma are peeled off.
On the other hand, this utility model provides a kind of and has been used to recover, rebuild or tissue transplantation's device of alternative patient tissue, comprise: mammalian epithelial tissue segment thickness, biodegradable, it comprises lamina propria or tela submucosa or sarolemma, and not having an epithelial mammal basement membranes of epithelium, described thus device recovers, rebuilds or alternative patient's tissue.
In a preferred implementation, described basement membranes of epithelium is positioned on the surface of described compositions.
On the other hand, this utility model provides the device of a kind of patient's who is used for the derived need tissue repair ill, damaged or repair of damaged tissues, wherein said device comprises the epithelial mammal basement membranes of epithelium that do not have from epithelial tissue, wherein when placing when contacting with described ill, damaged or damaged tissues, described device is induced the reparation of described ill, damaged or damaged tissues.
On the other hand, this utility model provides devitalized tissue's regenerating composition, comprises basement membranes of epithelium as the part that is used for tissue repair or regenerated substrate or support.Than the above-mentioned tela submucosa substrate that does not comprise basement membranes of epithelium, in inactivation mammalian tissues regenerating composition, comprise endogenous cell amplification and organized renewing in the body that basement membranes of epithelium causes improving.For the purpose of this utility model, inactivation is meant acellular or essentially no cell.For the purpose of this utility model, basement membranes of epithelium is meant the complete basement membranes of epithelium of at least a portion.
According to this utility model, be used for the mammal basement membranes of epithelium that mammalian tissues reparation or regenerated preferred inactivation substrate comprise at least a portion, preferably whole basement membranes of epithelium, and the lamina propria that is close to this basement membrane below.When putting into when contacting inactivation substrate of the present utility model recovery or replace diseased, damaged or disappearance tissue with host tissue.In a preferred implementation, this utility model comprises that customization is shaped to meet the inactivation substrate of ill or defective tissue.In a specific implementations, substrate comprises the substrate thin slice that derives from bladder, intestinal or any other mammalian epithelial tissue.In another embodiment, substrate is by means of being converted to fine granular, emulsion, gel or extract but injectable.Substrate of the present utility model can be served as the carrier that is used for medicament.The advantageous applications of substrate of the present utility model is the reparation or the recovery of heart tissue.Especially, substrate of the present utility model or compositions for recover or cardiac valve, interatrial septum, interventricular septum or the myocardium of alternative at least a portion of great use.For the purpose of this utility model, substrate and compositions are interchangeable terms.
In one embodiment, the inactivation compositions that is characterised in that of the present utility model, it comprises the lamina propria of basement membranes of epithelium and this basement membrane below of next-door neighbour.The lamina propria of this basement membrane below of basement membranes of epithelium and next-door neighbour and the nearly cavity segment of mammal epithelium and this lamina propria are peeled off.The mammalian epithelial tissue that uses at this utility model this respect preferably derives from bladder, intestinal or any other mammalian epithelial tissue.Other embodiments are characterised in that a kind of compositions, and it is shaped to meet valve of pulmonary trunk, aortic valve, a left side or right atrioventricular valve or the myocardium of ill or damaged cardiac valve such as at least a portion.
In another embodiment, of the present utility modelly be characterised in that a kind of compositions, comprise basement membranes of epithelium, lamina propria and tela submucosa.The cell of basement membranes of epithelium and lamina propria and epithelium and the sarolemma of mammalian epithelial tissue are peeled off.
In another embodiment, of the present utility modelly be characterised in that a kind of compositions, comprise the smooth muscle cell of basement membranes of epithelium, lamina propria and sarolemma, all are all peeled off with the epithelial cell of mammal epithelium.
Not only be confined to disclosed embodiment according to compositions of the present utility model.And the one or more layer that comprises epithelial tissue according to compositions of the present utility model is together with at least a portion, preferred whole complete basement membranes of epithelium.
On the other hand, this utility model is provided for inducing the method for the recovery or the reparation of ill or damaged heart tissue.A kind of method for optimizing of the present utility model comprises makes host tissue and the step that contacts from mammiferous inactivation substrate.This inactivation substrate comprises the basement membranes of epithelium of at least a portion and the mucosa of this basement membrane below of next-door neighbour.In a preferred embodiment, method of the present utility model comprises and utilizes tissue regeneration compositions of the present utility model to induce the endogenous epithelial repair.
Description of drawings
Accompanying drawing of the present utility model is not pro rata and emphasis is placed on usually and illustrates principle of the present utility model.
Figure 1A is the cutaway view of intestinal wall.
Figure 1B is the cutaway view of wall of urinary bladder.
Fig. 2 is according to the multilamellar patch of an embodiment of this utility model or the schematic cross sectional views of multilayer tissue's stent graft.
Fig. 3 is according to the multilamellar patch of another embodiment of this utility model or the schematic cross sectional views of multilayer tissue's stent graft.
Fig. 4 is according to the multilamellar patch of another embodiment of this utility model or the schematic cross sectional views of multilayer tissue's stent graft.
Fig. 5 is according to the multilamellar patch of another embodiment of this utility model or the schematic cross sectional views of multilayer tissue's stent graft.
Fig. 6 is the perspective schematic view according to multilayer tissue's stent graft of the lamella shape of an embodiment of this utility model.
Fig. 7 is the perspective schematic view according to multilayer tissue's stent graft of the tube shape of an embodiment of this utility model.
Fig. 8 is the schematic cross sectional views according to multilayer tissue's stent graft of the grain shape of an embodiment of this utility model.
Label declaration in the accompanying drawing:
A-epithelial cell B-basement membranes of epithelium
C-lamina propria D-tela submucosa
E-sarolemma 1-lining
The specific embodiment
As used herein, term " patch ", " support " or " device " and " structure " can exchange use in this utility model.In the following detailed description, when being described at patch and/or support or at support and/or device, other this utility model themes of not mentioning also can be suitable for.
Comprise available from the basement membranes of epithelium of the basement membranes of epithelium of mammalian epithelial tissue or at least a portion and the lamina propria part of adjacent underneath at least according to devitalized tissue of the present utility model reproducibility device or support.Be used for preferred epithelial tissue of the present utility model and include but not limited to bladder and other urogenital tracts, small intestinal, esophageal tissue and other gastrointestinal tract, skin, liver and tremulous pulse such as large artery trunks tissue and other cardiovascular system tissues.One preferred embodiment in, this utility model provides a kind of tissue transplantation device or support, comprise the basement membranes of epithelium of at least a portion and the lamina propria of adjacent underneath, separate from inner chamber epithelial cell, nearly chamber adventitia, serous coat and smooth muscle layer and submucosa tissue layer.According to this utility model, separate tissue or lift-off technology provide one deck inactivation extracellular matrix materials, and it comprises the basement membranes of epithelium (not having cell basically) of basement membranes of epithelium or at least a portion.Any residual cells element is removed as rinsing in hypotonic saline, peracetic acid or sterilized water by further treatment step then.
Therefore, with reference to Figure 1A and 1B, a preferred implementation of the present utility model comprises basement membranes of epithelium B and is called the biology orientation connective tissue of lamina propria C (its next-door neighbour and be positioned at the intestinal shown in Figure 1A, or the nearly chamber side of the basement membranes of epithelium B of the bladder shown in Figure 1B or any other epithelial tissue).This embodiment of the present utility model is characterised in that a plurality of parts of the lamina propria C of basement membranes of epithelium B and this basement membranes of epithelium of next-door neighbour B.Basement membranes of epithelium B and lamina propria C and epithelial cell A, tela submucosa D, sarolemma E and serous coat F peel off.Therefore, in this embodiment of this utility model, a plurality of parts of the mucosa H of adjacent body cavity L (being the inner chamber part of mucosa) form preferred periplast compositions.
In another preferred embodiment, refer again to Figure 1A and 1B, a kind of device of the present utility model or support comprise basement membranes of epithelium B, lamina propria C and tela submucosa D.Basement membranes of epithelium B, lamina propria C and tela submucosa D are from epithelial cell A, sarolemma E and serous coat F.In this embodiment, a plurality of parts that comprise epithelium sarolemma and submucosal mucosa H form a kind of preferred periplast compositions.
In another device or support, a preferred implementation of the present utility model comprises basement membranes of epithelium B, adjacent to lamina propria C, the tela submucosa D of this basement membranes of epithelium B and the sarolemma E of at least a portion.
With reference to figure 2, it shows according to the multilamellar patch of an embodiment of this utility model or the schematic cross sectional views of multilayer tissue's stent graft.Need to prove, for clear and easy to understand, only show a composite bed in this multilamellar patch in the accompanying drawings, but for the purpose of this utility model, can comprise a plurality of such composite beds, for example two, three, four, five, six even more a plurality of such composite bed.As shown in Figure 2, this multilamellar patch or support comprise a composite bed, wherein this composite bed comprise lining 1, at lamina propria C on the lining 1 and the basement membranes of epithelium B on lamina propria C, wherein by the compression and/or bonding this lining 1, lamina propria C and basement membranes of epithelium B form multilamellar patch or multilayer tissue's stent graft.Here need to prove,, a lining 1 can also be set above basement membranes of epithelium B according to using or application need.
As using in this utility model, lining 1 can be made by biocompatible plastic corrugated paper, non-woven fabrics or biocompatibility well known by persons skilled in the art or biological absorbable material.The effect of lining 1 mainly has been the support effect, and this is the same with common unguentum or patch.And as understood by a person skilled in the art, in use of the present utility model or application process, can remove lining 1 in advance as required.And wherein lamina propria C separates with basement membranes of epithelium B from dead mammiferous epithelial tissue for example bladder or any other epithelial tissue, and described basement membranes of epithelium B does not have epithelial cell and epithelial cell element.
For example, this composite bed is by form lining 1, lamina propria C and basement membranes of epithelium B vacuum compression together, and it is technology well known to those skilled in the art that vacuum compression forms composite bed.
Replacedly, this composite bed forms by using tissue glue well known by persons skilled in the art or medical type PUR that lining 1, lamina propria C and basement membranes of epithelium B are bonded together.
In a replaceable embodiment, with reference to figure 3, Fig. 3 shows according to the multilamellar patch of another embodiment of this utility model or the schematic cross sectional views of multilayer tissue's stent graft.As shown in the figure, wherein this multilayer tissue's stent graft or patch further comprise isolating inactivation tela submucosa D, wherein said tela submucosa D is close to described lamina propria C below and above lining 1, this tela submucosa D can be by for example compression and/or bonding and other layer formation one.
In a replaceable embodiment, with reference to figure 4, Fig. 4 is according to the multilamellar patch of another embodiment of this utility model or the schematic cross sectional views of multilayer tissue's stent graft.As shown in the figure, this multilayer tissue's stent graft or patch further comprise isolating inactivation sarolemma E, and wherein sarolemma E is close to below the described tela submucosa D and above lining 1, and this sarolemma E can be by for example compression and/or bonding and other layer formation one.
In a replaceable embodiment, with reference to figure 5, Fig. 5 is according to the multilamellar patch of another embodiment of this utility model or the schematic cross sectional views of multilayer tissue's stent graft.As shown in the figure, tissue transplantation's support wherein or multilamellar patch comprise the patch or the support of two identical single composite beds shown in Figure 2, can have more a plurality of such same compound layers at multilamellar patch of the present utility model or support, they can be for example by compression and/or the bonding one that forms.Wherein the order of connection of each composite bed formation multilamellar patch or support can be as shown in Figure 5 (1-C-B)-(1-C-B), also can be (B-C-1)-(1-C-B).Although it will be understood by those skilled in the art that only to show among Fig. 5 by two composite beds shown in Figure 2 forms the multilamellar patch, this utility model is not limited thereto.For example, can by a plurality of at Fig. 3 or Fig. 4 even composite bed shown in Figure 5 by compression or bonding multilamellar patch of the present utility model or the support of forming.
Patch of the present utility model or support can be any suitable shape, for example are lamella shape shown in Figure 6, and tubular form shown in Figure 7 perhaps is an annular shape shown in Figure 8.It perhaps is the grain shape (not shown).
In addition, this utility model provides a kind of and is used to recover, rebuilds, substitutes or multilayer tissue's stent graft of repair tissue, and it comprises a plurality of composite beds, and each composite bed comprises: lining 1; Isolating inactivation lamina propria C on described lining 1; And the isolating inactivation basement membranes of epithelium B on described lamina propria C, wherein said multilayer tissue stent graft forms by the described composite bed compression of two, three, four, five or six, bonding or their combination.
In a preferred implementation, described multilayer tissue stent graft further comprises isolating inactivation tela submucosa D or isolating inactivation sarolemma E, or further comprise isolating inactivation tela submucosa D and isolating inactivation sarolemma E, and also be by compression and/or bonding and other layers formation one.
The source of epithelial tissue
Be used for that multilamellar of the present utility model is amplexiformed, the material of tissue regeneration device or support usually preparation include but not limited to the tissue of pig, cattle and sheep from be used for the animal that meat is produced available from raising.Other warm-blooded vertebrates also can be used as tissue-derived, but make that from the bigger availability of the such animal that is used for meat production such tissue is preferred.Therefore, there is the cheap commercial source that is used to prepare according to the tissue of multilamellar patch of the present utility model or multilayer tissue's stent graft or device.Can have raising especially or the strain of genetic modification as some tissue-derived species.
For example, genetic modification becomes not have the pig of galactosyl, α 1,3 galactose (GAL epi-position) to produce the tissue-derived of this multilamellar patch or multilayer tissue's stent graft or device with acting on.Replacedly, the pig population of raising to there not being special pathogen can be used as tissue-derived.Can comprise embryonal tissue, commercially available weight, sex or the animal in sexual maturity stage available from the animal of any age group with acting on the tissue-derived mammalian tissues of producing this utility model compositions.
Basement membranes of epithelium tissue-derived
Bladder
A kind of preferred source of basement membranes of epithelium is the bladder of warm-blooded vertebrate shown in Figure 1B of pig.Excellent biological organization rebuilds performance and derives from and support and promote the cell growth and the basement membranes of epithelium composition that not have to invade, and allow and promote that endogenous cell adheres to, invades, the lamina propria of growth and the adjacent underneath of breaking up.Substrate (bladder substrate (UBM) hereinafter referred to as) comprises the lamina propria C of urothelium basement membrane B and adjacent underneath.In this embodiment, the extracellular matrix of the lamina propria C of basement membranes of epithelium B and adjacent underneath and epithelial cell A and tela submucosa D, basement membrane E and serous coat F peel off.Layer B, C, D, the E of patch of the present utility model or support or F be available from any warm-blooded vertebrate, but most preferably available from pig.Support of the present utility model is used for repairing or recovering bodily tissue and organ such as muscle skeleton and cardiovascular structures, skin and stomach intestinal tissue, apparatus urogenitalis and germinal tissue, nervous tissue, liver, kidney and head and neck tissue as biological support.
Preferably, tissue regeneration device or support comprise basement membranes of epithelium, bladder basement membrane preferably, and be positioned at the biological orientation molecular structure of next-door neighbour from this basement membranes of epithelium below of the bladder body of warm-blooded vertebrate.In this embodiment, basement membranes of epithelium and coelomic epithelium cell, nearly chamber adventitia, serous coat and smooth muscle tissue and submucosa tissue are peeled off.Than the implantation of describing before or inject vertebrate host to cause the tela submucosa transplantation group compound of repairing or substitute impaired, disappearance or deficient tissue or organ, tissue transplantation of the present utility model support or device have the tissue growth characteristic of remarkable excellence.
This utility model avoids completely losing basement membranes of epithelium, and produces tissue regeneration device or support, and it comprises the basement membranes of epithelium of at least a portion.In a preferred implementation, be complete to a great extent as the basement membranes of epithelium of determining by traditional group weave chemistry or immunohistochemistry technology and light or ultramicroscope.The gained inactivation material that obtains by this utility model with as in the patent of He ' 389, ' 508, describe to be used to prepare the tissue graft composition that derives from small intestinal and bladder opposite, its generation comprises tela submucosa but does not comprise the graft materials of basement membranes of epithelium.The step of before the preparation from the UBM of bladder body is different from, describing that is used for the submucosa tissue transplantation group compound that preparation describes in He ' 389, ' 508 patent.Transplant in the method for compositions being used for the submucosa tissue that preparation He ' 389, ' 508 patent describes, mucosa mechanically shifts out by denuding.
According to this utility model, UBM by from warm-blooded vertebrate for example pig shift out bladder body, and by at first this being organized in for example hypertoric saline of epithelium solution, most preferably in the 1.0N saline soak time scope 10 minutes to 4 hours the time interval and peeling off, and make.Be exposed to hypertoric saline solution and shift out epithelial cell from the below basement membrane effectively.The tissue that stays after initially peeling off program comprises the organized layer in basement membranes of epithelium and this nearly chamber of basement membranes of epithelium.This tissue then stands further to handle shifting out main nearly cavity tissue, but does not shift out basement membranes of epithelium.The nearly cavity segment of outside serous coat, tunica adventitia of artery, smooth muscle tissue, tela submucosa and lamina propria shifts out from the epithelial tissue that goes that stays by abrasion or by the combination of enzymatic treatment, hydration and pattern.The machinery of these tissues shifts out that Adson-Brown tweezers and Metzenbaum shears shift out mesentery tissue by for example utilizing, and the vertical wiping motion that utilizes scalpel handle or be wrapped in other hard objects in the wet gauze is wiped sarolemma and finished.The known organizational groups compound that derives from the animal epithelial tissue before this tissue is different from, it comprises complete to a great extent basement membranes of epithelium in this utility model.Tissue can further be handled by rinsing in hypertoric saline, peracetic acid or sterilized water.The additive method that is used to shift out organized layer for example microtome also can be used for obtaining tissue transplantation of the present utility model device or support.
Being used for preparation is not limited to utilize bladder body as parent material according to tissue regeneration device of the present utility model or support.Also can be applicable to other initial tissues, for example skin, esophagus, stomach and intestinal tissue according to this utility model.
After preparing UBM according to this utility model, the gained organization bracket is made of the material (its main (promptly greater than 90%) is made of the extracellular matrix that comprises basement membranes of epithelium (ECM)) of about 10-120 micron thickness.This material can keep or can not keep some and comprise original structure such as capillary endothelial cell or fibrocellular cell element.These cell elements are removed by being exposed to peracetic acid (as the part of sterilizing biological materials) subsequently.This material is different from submucosa tissue transplantation group compound on its histological appearance and structure thereof, because the collagen ECM closely knit, that partly change in a organized way that distinguishes the level and smooth basement membranes of epithelium of surface of internal cavity and distinguish surface, nearly chamber.ECM material use H﹠amp; E dyes pink and dyes blueness with the Masson trichrome stain.
Skin, esophagus
Similarly, in that prepare the step used the tissue regeneration compositions from other epithelium organs with the organized layer that is similar to bladder such as skin or esophagus identical with the above-mentioned step that is used to prepare UBM.The same with bladder substrate, the material that stays after shifting out epithelial cell, serous coat, sarolemma and nearly chamber lamina propria comprises the basement membranes of epithelium and the adjacent lamina propria of at least a portion.
Small intestinal
A kind of tissue regeneration device of the present utility model or support also derive from the gastrointestinal epithelial tissue, as small intestinal.Comprise that in preparation the step in the tissue regeneration compositions of lamina propria (being called SIM) of at least a portion small intestine epithelium basement membrane and adjacent underneath is similar to the step of above-mentioned formation UBM.Can use 1.0N saline to come to shift out epithelial cell from basement membranes of epithelium.Be used to shift out epithelial a kind of replaceable method and be epithelial tissue is immersed in detergent such as nonionic detergent with 0.025～1% concentration, for example Triton X-100 reaches 5 minutes to several hours.
In one embodiment, the tissue regeneration composite bed of peeling off that derives from epithelial tissue stores with chilled water and state or at room temperature stores after the air drying.Replacedly, this tissue regeneration composite bed lyophilizing and with dewatering state in room temperature or freezingly store down.In another embodiment, this tissue regeneration composite bed can shred and by protease for example in pepsin or the trypsin this material of digestion reach be enough to dissolve this tissue and form basically homogeneous solution time interval make its fluidisation.The viscosity of dissolved material can change to form gel, gel-aerosol or fully liquid state by regulating pH.The preparation example of fluidized intestinal submucosa is as being described in U.S. Patent No. 5,275, and is in 826, by reference that it is incorporated herein clearly.
In another embodiment, this utility model has been considered the tissue regeneration device of powder type or the application of support.In one embodiment, after removing lining, the tissue regeneration device of stratiform form or support are 0.005mm by chopping or crushing release liner to produce size range
2To 2.0mm
2Granule and form.The material that never needs organized layer to peel off is for example freezing in liquid nitrogen, to carry out the crushing program.Replacedly, this material dehydration is to implement the crushing program.The material of crushing form then lyophilizing to form essentially no water particle shape tissue regeneration support or device.
Tissue transplantation of the present utility model device or support are applicable to many operations and non-operation application, are used to induce the purpose of reconstruction capability wound healing and organized renewing.For example, they are used for substituting a plurality of parts of cardiac valve, tremulous pulse, vein, bladder, liver, gastrointestinal of impaired, ill or disappearance or they and can repair or the template of alternative head and neck structure with acting on.With the arbitrary form in its multiple solid or the fluidized forms, this material can be used as support, be used for epidermis or crust reparation, be injected into various health sphincters such as urinary system device sphincter or esophagus or stomach sphincter, be folded into pipe or part pipe and be used to recover nervous tissue, perhaps extrude or be molded as and be suitable for its any form as the application of tissue regeneration compositions as pipeline.Tissue regeneration patch of the present utility model, support or device can sew up with its solid thin-sheet form and put in place, place wound or body part with gel form, and perhaps liquid or particle form are injected together.When body inner target tissue place with mammal source, devitalized tissue's compositions (basement membranes of epithelium that comprises at least a portion) is when contacting, the growth of tissue transplantation of the present utility model device or stent-induced endogenous tissue comprises epithelium and connective tissue.
Bladder substrate (UBM)
The UBM compositions comprises I type and IV Collagen Type VI, glycosaminoglycan class at least, comprises hyaluronic acid, chondroitin sulfate A and B, heparin and heparin sulfate.In addition, one or more basic fibroblast growth factors, vascular endothelial cell growth factor and TGF-β exist in UBM.
The physical property of UBM part characterizes.UBM has the single shaft intensity (via the Unite States Standard that is used to test with the material under the 1 inch per minute clock tractive, utilizing the material testing system machine to detect) of wide about 0.1-2.0 pound of every 1.0cm.It is the about 1.0-4.0 newton of each lamella (N) that the stitching of material keeps intensity, particularly, is 4-18N and is 30N-120N for 30 layers of substrate for 4 layers of substrate.Ball explosion bulge test failure active force (ball bursttest failure force) is about 4-10 pound for each layer, particularly, for 8 layers be 32-80N, for 4 layers be 16-40N, and be 36-120N for 12 layers.
Porosity exponent is defined as every cm under 120mmHg pressure
2/ minute flow through the water yield of material.The water voids degree makes the side of UBM be different from opposite side according to flow direction.The flow velocity of the basement membranes of epithelium side of the water of water about 20% from nearly chamber effluent to substrate flows to nearly chamber side from basement membranes of epithelium.UBM also has viscoelastic property.
UBM can carry out disinfection and not lose the ability that it induces the endogenous tissue growth by in the multiple standards method any.For example, after the rinsing, material can be handled by ethylene oxide, gamma-radiation is handled (0.5 to 2.5mRad), gaseous plasma sterilization or the processing of e-bundle and carried out disinfection in the peracetic acid of saline and 0.05% to 1.0%.Material also can cause that the crosslinked glutaraldehyde processing of protein material carries out disinfection by utilization, but this processing substantially changes this material, make its very slow quilt absorb again or be not absorbed, and the host of inducing different types rebuilds, this resembles the scar tissue more nearly and forms or capsuleization, rather than constructivity is rebuild.The crosslinked carbodiimide or the liquid that reduces phlegm and internal heat (dehydrothermal) or photooxidation method of also can utilizing of protein material induced.
Following example will be used for better confirming successfully realization of the present utility model.As noted above, patch of the present utility model, support or device can be selected according to the needs of using.Lining can keep also and can remove in application.
For example
As patch of the present utility model, support and/or device use for example, it is damaged that patch of the present utility model, support and/or device are applied to cardiac valve.As understood by a person skilled in the art, support of Pi Luing and/or device may be used on other tissue regeneration support or devices herein, it derives from the epithelial tissue source that is different from bladder, from the mammal source that is different from pig, and can be applied to the tissue defect that is different from cardiac valve.In addition, tissue regeneration support of the present utility model and/or device can be used with the form of the thin slice that is different from material or composite wafer, for example, tissue regeneration support of the present utility model and/or device can be used as extract, gel form, powder type, tubular form, sheet form or mix as bar, rope or support or with other medicaments (for example somatomedin and gene outcome) and use.Tissue regeneration support of the present utility model and/or device can be molded as a kind of form to be fit to the application-specific of health.The preparation of organizing fluidized forms is in U.S. Patent No. 5,275, describes in 826, and its content is incorporated herein by reference.And the solid thin-sheet of tissue and the preparation of bar be in U.S. Patent No. 5,7 11, describes in 969, and its content is incorporated into this paper by reference.
Cardiac tissue repair
According to embodiment of this utility model is to be used to repair or the tissue regeneration device or the support of alternative heart tissue.Heart tissue includes but not limited to ill, impaired or the disappearance heart tissue, comprise film and all cardiac valvies and relevant lobe leaf between myocardium, visceral pericardium, endocardium, pericardium, room film and chamber, comprise that a plurality of parts of valve of pulmonary trunk, aortic valve, right atrioventricular valve and left atrioventricular valve and the adjacent vascular of heart comprise pulmonary artery, pulmonary vein, postcava and superior vena cava.
In this embodiment of the present utility model that this paper discloses, tissue regeneration support and/or device can prepare the Vesica sus domestica from as mentioned above, and the cardiac valve before body and allosome that is used as valve of pulmonary trunk in 5 pigs and 3 Canis familiaris L.s substitutes the lobe leaf.
Tissue regeneration support of the present utility model and/or device can utilize shears or tweezers to cut to be fit to the valve of pulmonary trunk frontal lobe when operation.Tissue regeneration support of the present utility model and/or device can directly be seamed to annulus at valve pedestal place.For example, when using this utility model single sheet support shown in Figure 6, in this thin embodiment, the basement membranes of epithelium side of tissue regeneration support of the present utility model is positioned at the nearly chamber of the right ventricle side that substitutes the lobe leaf, and directly is seamed to the annulus of valve of pulmonary trunk.In addition, when two thickness embodiments of tissue regeneration support of the present utility model are for example used this utility model two thickness support shown in Figure 5, the tissue regeneration support can fold and make basement membranes of epithelium be positioned at two surfaces that substitute the valve of pulmonary trunk leaf, be on ventricle and the artery surface, and directly be seamed to the annulus of valve of pulmonary trunk.
Canis familiaris L. that is used to test and the valve of pulmonary trunk of pig substitute 6 weeks of back and checked in 12 weeks at valve.A Canis familiaris L. substitutes back 5 months at the lobe leaf and checks.Utilize the lobe leaf that normal structure is fixing and histopathology learns a skill and checks results.
Substitute 6 weeks of back at the lobe leaf, the epithelization that substitutes the lobe leaf presents on whole lobe leaf surface.The cell that moves on the lobe leaf surface is by to the immunofluorescence dyeing of the von Willebrand factor and stained positive shows, these cells are endothelium origins.In some lobe leaves, some endotheliocytes have the feature of early progenitor cell.Infiltration of the neovascularization of extracellular matrix, endotheliocyte and deposition are observed to originate from the host tissue at valve of pulmonary trunk annulus place and extend to and are substituted in the lobe leaf.
Substitute 12 weeks and 5 months of back at the lobe leaf, do not have discernible original structure reproducibility support and install can and the recovery of lobe leaf finish.Comprise not having endothelium to invade to substitute in the lobe leaf, do not have thrombosis and do not have calcification or cell-mediated alternative lobe leaf repels in the unexpected discovery of the time point of all inspections.In addition, at the time point of all inspections, the shape that substitutes the lobe leaf does not change from the leaf shape of original lobe.
Substitute 8,12,16 and 20 weeks of back at valve, the ultrasonic investigation of the valve of pulmonary trunk of pig shows it is the valve of being competent at.
In this utility model another embodiment aspect this, the tissue regeneration support of fluidisation, powdered or pulp form and/or device can be applied to adjacent to ill or damaged heart tissue, to promote the endogenous tissue reparation.For example, fluidisation tissue regeneration support or device are injected into adjacent to congenital ventricular septal defect, congenital atrial septal defect or inject the inner chamber of opening ductus arteriosus and grow with the endogenous of organizing that promotes these zones.
Tissue regeneration support or device are applied to heart tissue and finish by adopting multiple different modus operandi.For example, Minimally Invasive Surgery is used at peritoneoscope auxiliary down near the operation on heart position.Replacedly, implement thoracotomy.Tissue regeneration support and/or device are delivered to operative site with its preparation form such as thin slice, ring, bar or as in injectable, powder or the pulpous state form any.Tissue regeneration support and/or device thin slice or bar be before the operative procedure or during customization be suitable for specific heart and use.Tissue regeneration support and/or device thin slice or bar utilize suture, staple, tissue glue or any other mode well known by persons skilled in the art fixing adjacent to or in damaged or diseased heart tissue.
In according to another mode of the present utility model, multilamellar patch of the present utility model can utilize shears or tweezers to cut to be fit to the valve of pulmonary trunk frontal lobe when operation after removing lining.Multilamellar patch of the present utility model can directly be seamed to annulus at valve pedestal place.For example, when using this utility model single sheet patch shown in Figure 6, the basement membranes of epithelium side of multilamellar patch of the present utility model is positioned at the nearly chamber of the right ventricle side that substitutes the lobe leaf, and directly is seamed to the annulus of valve of pulmonary trunk.Through postoperative observation, the result of acquisition is the same with the result of above-mentioned support and/or device.
Use 2
The substrate that is used for the cell in vitro expansion
Human microvascular endothelial cell (HMVEC) forms endothelium, one in vivo on the basement membrane with the cell monolayer of the mode formative tissue of simulation epithelium.Utilize that isolating HMVEC is external to be studied, it is laid in the basement membranes of epithelium side of (i) tissue regeneration support and/or device thin slice; (ii) on the surface, nearly chamber of tissue regeneration support and/or device; (iii) on the submucous layer of small intestine tissue graft composition (SIS) according to the method preparation that in the patent of He ' 178, ' 508, discloses; And (iv) on the urinary bladder submucosa tissue compositions (UBS) according to the method preparation that discloses in ' 389 patents.
Through 3 days growth, HMVEC grew in the substrate and does not form the fused cell layer, no matter whether HMVEC is laid on the inner chamber or nearly surface, chamber of SIS or UBS after the pawnshop was put on the surface of SIS and UBS.
Be laid in the lip-deep HMVEC in the nearly chamber of UBM and grow in the substrate, increase and break up in the mature endothelial cell.The lip-deep HMVEC in the nearly chamber of SIS and UBS is the same with being laid in, and the fused layer of HMVEC does not form on surface, the nearly chamber of UBM after growth in 3 days.
Opposite with known tissue regeneration compositions such as SIS before in these researchs other with UBS, the HMVEC that is laid on the basement membranes of epithelium side (near chamber) of tissue regeneration support and/or device thin slice is attached to tissue regeneration support or device after growth in 3 days, amplification, differentiation also form the fusion monolayer.
Use 3
Considered tissue transplantation of the present utility model device and/or support can be used for inductor inner tissue reparation or substitute, comprise connective tissue such as ligament, tendon, cartilage, bone, joint, and muscle, epithelial tissue such as bladder, and its hetero-organization of urogenital tract, stomach, its hetero-organization of esophagus and gastrointestinal, liver, nervous tissue, the head and neck tissue, skin, with its hetero-organization, utilize in U.S. Patent No. 4,902,508,4,956,178,5,281,422,5,352,463,5,554,3 89,5,275,826,4,902,508,5,372,821,5,445,833,5,516,533,5,573,784,5,641,518,5,695,998,5,711,969,5,755,791,5,762,966 and 5, the same program of describing in 885,619 is incorporated into this paper by reference with their content.Tissue transplantation of the present utility model device and/or support can also use with the synthetic or non-synthetic polymer that is used for organized renewing.
Claims (24)
1. multilamellar patch comprises:
One or more composite beds, each composite bed comprises:
Lining (1);
Isolating inactivation lamina propria (C) on described lining (1); And
Isolating inactivation basement membranes of epithelium (B) on described lamina propria (C),
Wherein said multilamellar patch is by the compression and/or bonding formation of described composite bed.
2. multilamellar patch according to claim 1 further comprises isolating inactivation tela submucosa (D), and wherein said tela submucosa (D) is close to described lamina propria (C) below.
3. multilamellar patch according to claim 2 further comprises isolating inactivation sarolemma (E), and wherein said sarolemma (E) is close to described tela submucosa (D) below.
4. one kind is used to recover, rebuilds, substitutes or multilayer tissue's stent graft of repair tissue, comprising:
One or more composite beds, each composite bed comprises:
Lining (1),
Isolating inactivation lamina propria (C) on described lining (1); And
Isolating inactivation basement membranes of epithelium (B) on described lamina propria (C),
Wherein multilayer tissue's stent graft is by the compression and/or bonding formation of described composite bed.
5. multilayer tissue according to claim 4 stent graft, wherein said lamina propria (C) separates from dead mammiferous epithelial tissue with basement membranes of epithelium (B), and described basement membranes of epithelium (B) does not have epithelial cell and epithelial cell element.
6. multilayer tissue according to claim 4 stent graft, wherein said compression is undertaken by vacuum compression.
7. multilayer tissue according to claim 4 stent graft, wherein said bondingly undertaken by using-system glue or medical type PUR.
8. multilayer tissue according to claim 4 stent graft further comprises isolating inactivation tela submucosa (D), and wherein said tela submucosa (D) is close to described lamina propria (C) below.
9. multilayer tissue according to claim 8 stent graft further comprises isolating inactivation sarolemma (E), and wherein said sarolemma (E) is close to described tela submucosa (D) below.
10. according to each described multilayer tissue stent graft among the claim 4-9, wherein said tissue transplantation support is thin slice, pipe, ring or coating of particles.
11. one kind is used to recover, rebuilds, substitutes or multilayer tissue's stent graft of repair tissue, comprising:
A plurality of composite beds, each composite bed comprises:
Lining (1),
Isolating inactivation lamina propria (C) on described lining (1); And
Isolating inactivation basement membranes of epithelium (B) on described lamina propria (C),
Wherein said multilayer tissue stent graft forms by compression and/or bonding two, three, four, five or six described composite beds.
12. multilayer tissue according to claim 11 stent graft further comprises isolating inactivation tela submucosa (D) or isolating inactivation sarolemma (E), or further comprises isolating inactivation tela submucosa (D) and isolating inactivation sarolemma (E).
13. tissue transplantation's device comprises: separate lamina propria and mammal basement membranes of epithelium from mammalian epithelial tissue, the epithelial cell of wherein said mammal basement membranes of epithelium and lamina propria and described mammalian epithelial tissue is peeled off.
14. tissue transplantation's device comprises: separate tela submucosa and mammal basement membranes of epithelium from mammalian epithelial tissue, the epithelial cell of wherein said mammal basement membranes of epithelium and tela submucosa and described mammalian epithelial tissue is peeled off.
15. tissue transplantation according to claim 13 device, wherein said mammalian epithelial tissue comprises the epithelial tissue from bladder.
16. tissue transplantation according to claim 14 device, wherein said mammalian epithelial tissue comprises the mammalian epithelial tissue from bladder.
17. a device that is used to induce the mammalian tissues reparation comprises:
Isolating inactivation mammal basement membranes of epithelium, wherein said mammal basement membranes of epithelium derive from bladder and do not have epithelial cell and the epithelial cell element; And
Lamina propria.
18. a device that is used to recover, substitute or repair urogenital tract tissue, stomach intestinal tissue, skin histology, nervous tissue, cardiovascular organization or connective tissue comprises:
The lamina propria of the described basement membrane of inactivation mammal basement membranes of epithelium and next-door neighbour below, wherein said basement membranes of epithelium does not have epithelial cell and epithelial cell element.
19. a structure that is used to recover, rebuild or repair described urogenital tract tissue, cardiovascular organization, stomach intestinal tissue, skin histology, nervous tissue or connective tissue comprises:
The inactivation basement membranes of epithelium and the lamina propria of at least a portion of peeling off from mammalian epithelial tissue.
20. an inactivation structure that is used to induce the mammalian tissues defect repair comprises: the lamina propria of the described basement membrane of isolating inactivation mammal basement membranes of epithelium and next-door neighbour below, wherein said basement membrane derives from bladder or small intestinal.
21. an inactivation structure comprises:
(a) lamina propria of the described basement membranes of epithelium of mammal basement membranes of epithelium and next-door neighbour below, the epithelial cell of the epithelium of wherein said basement membrane and lamina propria and mammalian epithelial tissue lamina propria and nearly cavity segment is peeled off; Or
(b) smooth muscle cell of mammal basement membranes of epithelium, lamina propria and described sarolemma, the epithelial cell of wherein said basement membrane, lamina propria and smooth muscle and mammal epithelium is peeled off; Or
(c) mammal basement membranes of epithelium and tela submucosa, the epithelium of wherein said basement membrane and tela submucosa and mammalian epithelial tissue and the epithelial cell of sarolemma are peeled off.
22. one kind is used to recover, rebuild or tissue transplantation's device of alternative patient tissue, comprises:
Mammalian epithelial tissue segment thickness, biodegradable, it comprises lamina propria or tela submucosa or sarolemma, and does not have epithelial mammal basement membranes of epithelium, described thus device recovery, reconstruction or alternative patient's tissue.
23. device according to claim 22, wherein said basement membranes of epithelium are positioned on the surface of described compositions.
24. the device of ill, damaged or repair of damaged tissues of the patient who is used for the derived need tissue repair, wherein said device comprises the epithelial mammal basement membranes of epithelium that do not have from epithelial tissue, wherein when placing when contacting with described ill, damaged or damaged tissues, described device is induced the reparation of described ill, damaged or damaged tissues.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2009200044822U CN201510424U (en) | 2009-09-11 | 2009-09-11 | Patch, tissue transplantation supporting frame, tissue regenerative device and structure |
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| Application Number | Priority Date | Filing Date | Title |
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| CN2009200044822U CN201510424U (en) | 2009-09-11 | 2009-09-11 | Patch, tissue transplantation supporting frame, tissue regenerative device and structure |
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| CN201510424U true CN201510424U (en) | 2010-06-23 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103622762A (en) * | 2012-08-23 | 2014-03-12 | 上海国睿生命科技有限公司 | Method for constructing tissue engineering cartilage |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103622762A (en) * | 2012-08-23 | 2014-03-12 | 上海国睿生命科技有限公司 | Method for constructing tissue engineering cartilage |
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