KR100342384B1 - Tracheal prothesis with transplanted autogenous mucosa - Google Patents

Abstract

If the airways that make up the body are damaged or deleted, use an airway implant with autograft mucosa with adhesive to replace the damaged or missing airway. Successfully supplement the airway section.

Description

Tracheal prothesis with transplanted autogenous mucosa

[TECHNICAL FIELD OF THE INVENTION]

The present invention relates to an autologous mucosal airway prosthesis, and more particularly, when the airway constituting the body is damaged or deleted to replace the airway damaged or deleted with a prothesis. The present invention relates to an airway prosthesis in which an autologous mucosa is fixed to an airway prosthesis using an adhesive so as to be well integrated with existing tissue.

The present invention also relates to the use of gelatin, which uses gelatin to bond prostheses with internal tissues.

[Private Technology]

A wide range of airway ablation may be needed to treat patients with a wide range of airway diseases, whether malignant or traumatic. In most cases, it is not appropriate to anatomize the airway immediately after a wide range of airway resections, since it was almost impossible to treat a wide range of airway deletions with airway prostheses (Grillo HC. Circumferential resection and reconstruction of the mediastinal and cervical trachea.Annn Surg 1968; 55: 374-388) A widespread use of the airway fistula, which primarily leaks the airway into the skin of the neck.

On the other hand, a number of studies have been carried out with natural epithelial and cartilaginous rings as a viable method for treating airway defects, but have not been successful (Lenot B, Macchiarini P, Delmet E, et al. Tracheal allograft replecement.An unsuccessful method.Eur J Cardiothorac Surg 1993; 7: 648-652). The failure of this study had two major problems: graft ischemia and immunorejection.

Recently, however, graft ischemia has begun to suggest a path of resolution: indirect revascularization using omentum or muscle pedicle flaps (Nakanishi R, Shirakusa T, Takachi T. Omentopexy). for tracheal autografts.Anne Thorac Surg 1994; 57: 841-845). In some studies, four to five grafts showed blood vessel formation, although the safe allograft length was not determined, and the experimental animals survived for several months.

Immune rejection has not been controlled yet. Although crypreservation or post-implantation radiation and / or immunosuppression has been proposed and studied, it has not yet been safely applied in clinical applications, and experimental clinical applications have not been successful (Hokomise). H, Kuni K, Wade H et al. High-dose irradiation prevents rejection of cannine tracheal allografts.J Thorac cardiovasc Surg 1994; 107: 1391-1397).

The above two problems of allografts are sometimes solved but create another serious problem of the availability of grafts. The designation and storage of cryopreserved airways as an allograft bank seems convincing, but in reality it is unlikely to be feasible in the field of allograft transplantation because it is very difficult to collect allografts in the airway.

The fundamental way to cure a wide range of airway diseases listed above is the development of an airway implant graft. However, the development of airway implant grafts has not been very successful because of dehiscence and stenosis of the anastomosis (Nelson RJ, Goldberg L, White RA, Shors E, Hirose FM. Neovascularity of a tracheal prosthesis / tissue complex. J Thorac Cardiovasc Surg 1983; 86: 800-808). In other words, the implanted airway epithelialization did not work well and chronically ruptured and eroded the main vascular system by stimulating the formation of new flesh for tissue formation.

Neville, Bolanowiski and Soltanzadeh stated that the six characteristics of an ideal airway implant were: (1) impermeable to air, (2) of moderate hardness, (3) well-received by the host, (4) minimally inflammatory and coalescing by surrounding tissues, and (5) binding Tissue forming cells and lumens are not invaded by bacteria, and (6) respiratory epithelium can grow along the lining of artificial airways (Nevelle WE, Bolanowski PJP, Soltanzad, H. Prothetic reconstruction of the trachea and carina.J Thorac Cardiovasc Surg 1976; 72: 525-538).

Most of the airway cochlear implants to date have not satisfied the above requirements, and in particular, it was the most difficult problem to allow the respiratory epithelium to grow along the inner wall of (6). Recently, a tissue engineering method of inducing epithelial lining on the prosthesis prior to the implantation of the airway prosthesis has been attempted, but the tissue culture process has been too complicated for clinical use.

Gelatin, also known as glue, is an inducible protein that is extracted when hot water is used to treat collagen constituting animal skins, tendons, bones, etc., and irreversibly soluble proteins as a result of the breakdown of salt or hydrogen bonds between peptide chains of collagen To change. The molecular weight of the gelatin is about 23,000, and when the aqueous solution with a concentration of 1% or more is cooled to 40 ° C. or lower, it becomes an elastic gel, and when heated, it melts again and is reversibly sol-gel converted. The temperature of gelation varies with concentration, type and concentration of coexisting salts, and pH, and the gelatine solution boiled for a long time does not gel again. Gelatin has been used as a substrate for proteases, especially for active dyeing after gel electrophoresis because gelatin is completely different from collagen and is degraded by various proteases. Gelatin is not antigenic and has been used as a medium or edible and as an adhesive, but has not been reported to be used for adhesion of tissues in the body.

An object of the present invention is to provide a clinically usable airway prosthesis by solving the problem of the airway prosthesis used in the conventional airway implantation by transplanting autologous mucosal tissue.

It is also an object of the present invention to propose the use of an adhesive for adhesion between body tissue and prosthesis.

Figure 1 shows the artificial airway produced,

Figure 2 shows the artificial airway surrounded by the long-term,

3 is an X-ray photograph showing the growth of blood vessels into the mucosal cells transplanted from the blood vessels of the long-term,

4 is a tissue photograph showing that the transplanted mucosal cells are growing well.

In order to achieve the object of the present invention, the present invention relates to a cylindrical tube comprising a cylindrical tube and two or more hoops to reinforce the tube and (b) an adhesive on the inner surface of the cylindrical tube. To provide an airway prosthesis containing autograft mucosal tissue adhered to the tissue.

In another aspect, the present invention provides a method for treating a human airway that complements the airway portion deleted by the airway prosthesis, comprising the steps of: (a) preparing a prosthesis coated with an adhesive; Implanting mucosal tissue and (c) surrounding the implanted airway implant with an omentum.

The present invention also provides an adhesive comprising only gelatin for use in adhering the prosthesis and internal tissues of the body.

Hereinafter, the present invention will be described in detail.

The airway prosthesis coated with the autograft mucosal tissue provided by the present invention is provided to compensate for the airway deleted in the airway incision of the human body.

In the airway prosthesis of the present invention, the shape of the airway prosthesis is preferably in the form of a cylinder so as to resemble the shape of the airway lumen. In addition, the size of the airway prosthesis is preferably larger than the diameter of the body airway into which the diameter is inserted, more preferably 25 to 45 mm, the length can be adjusted according to the length of the deleted airway, but longer than the deleted airway part Preferably, more preferably, the length of the airway prosthesis is 50 to 70 mm.

In addition, the cylinder-shaped tube of the present invention is preferably made of a mesh tissue, the material that can be used in the mesh tissue is harmless to the human body can be used for most of the network tissue generally inserted into the human body. Preferred are non-biodegradable materials consisting of proline, polyurethane, polyethylene, silicone, polytetrafluoroethylene and polypropylene and biodegradable including polylactic exit, lactic Axis / glycol copolymers and cat guts. It is preferably selected from the group consisting of substances.

In addition, the ring of the present invention is used to maintain the shape of the tube in the form of a cylinder. The ring is preferably two or more, and may increase the number of rings depending on the length of the airway prosthesis to be inserted. The spacing of the rings is preferably 4 to 6 mm. In addition, in the size of the ring, the diameter is preferably similar to the diameter of the tube in the form of a cylinder, the thickness is preferably 0.3 to 1.1 mm, the width is preferably 0.3 to 1.1 mm. In addition, the material of the ring is harmless to the human body can be used to insert all of the substances in the human body, preferably a material such as mesh tissue. Cartilage tissue cultured using histological techniques can also be used in place of rings.

In addition, the adhesive used in the present invention acts to facilitate early epithelialization in the airway prosthesis by improving adhesion between the airway prosthesis and the autologous mucosa or long mesh, and is degraded in vivo and nontoxic to humans and tissues. Any adhesive that does not cause an immunological rejection can be used. Preferably, the degradation time in vivo is between 46 and 50 hours. More preferably, the adhesive is gelatin, and more preferably, the gelatin is in a sol state. When applying the airway prosthesis with an adhesive, the thickness of the adhesive layer is preferably about 0.8 to 1.2 mm. When applying gelatin, dissolve in water and apply.

In another aspect, the present invention is a method for treating airway deficiency in the human body to complement the airway part deleted by the airway prosthesis, (a) implanting the autologous mucosal tissue in the artificial prosthesis coated with the adhesive, (b) the adhesive applied And inserting the artificial prosthesis into the deleted airway deletion portion and (c) enclosing the inserted airway implant portion with an omentum.

On the other hand, the present invention provides an adhesive comprising a gelatin used to bond the artificial insert and the internal tissue of the body, the artificial insert is an artificial graft inserted into the body to complement or replace the organs, muscles, tissues, etc. in the body it means. Preferably, the graft is cylindrical in shape, and more preferably, the graft is an airway prosthesis. In addition, the internal tissue of the body may be any tissue generally present in the body, such as organs, membranes, muscles in the body, and preferably, the tissue has a membrane shape, and more preferably, the tissue is mucosal or long-term ( omentum) is even better.

Hereinafter, examples of the present invention will be described. However, the following examples are intended to illustrate the invention and not to limit the invention.

Example 1 Preparation of an Airway Prosthesis with an Adhesive Coated

Adhesive coated airway prostheses were made of proline mesh, polypropylene ring and gelatin. Ten polypropylene rings 30 mm in diameter, 1 mm thick and 1 mm wide were bonded to a cylindrical tube (CR Bard. Inc., Billerica, Mass) with a proline mesh at intervals of 5 mm.

In addition, the airway prosthesis in the form of a cylinder with the polypropylene ring was coated with gelatin to prepare an airway prosthesis in which an adhesive was applied. The airway prosthesis to which the gelatin (gelatin purchased) was applied (coated thickness) was dried and sterilized with EO gas. 1 is a photograph showing the airway prosthesis produced by the above method.

Example 2 Surgery Procedure

Eight hybrid dogs, 15-20 kg, were anesthetized after anesthesia with 10-15 mg / kg intravenous injection of thiopental sodium. The test dogs were subjected to oral intubation after injection of 0.1 mg / kg bromine becuronium. An airway inner tube with a cuffed inner diameter of 6.0 mm was connected to a ventilator (NARKOMED 2B, North America Drager, USA). Anesthesia was maintained using a ventilator by inhalation of gas (O ₂ 1 L / min, N ₂ O 1 L / min, halotane 1 to 1.5%).

The experimental dogs were fixed, shaved and disinfected. After the disinfection, the abdomen of the dog was incised from the middle up. Oral mucosa was removed from the oral cavity of the dog and soaked in antibacterial solution. The mucosa was placed on the tacky surface of the gelatin-coated airway prosthesis. The airway prosthesis was enclosed in a long mesh. 2 is a photograph of an artificial airway surrounded by a long snow. The adhesion between the airway prosthesis and the perforation was very good. The adhesion between the mucosa and the airway prosthesis was also very good in all airway prostheses. The lumen surface of all airway prostheses was completely covered with deposited host connective tissue and air tightness was also good.

Example 3 Nursing after Surgery

The dogs were injected intravenously with 500 mg of cefamazine on the day of surgery and intramuscular injection with 250 mg of sefazin daily for three days after surgery. All animals were cared for by humans according to the National Institutes of Health's Guide to the Care of Laboratory Animals (NIH Publication 85-23, 1985).

All eight dogs used in the experiment were able to walk and eat after eight hours of surgery. All survived and had good health during the experiment and had no subjective symptoms.

Example 4 Histological Examination

Dogs used in the experiment were anesthetized in the same manner as mentioned in Example 2. The dog's belly was again opened through an incision from the middle up. The inserted airway prostheses were excised and washed with saline and fixed with 10% formalin solution for histological study. The mucosal cell viability of the lumen surface was examined by hematoxylin and eosin staining. All dogs were firmly connected to long-term tissue with the exception of the two dogs with oral mucosa folded. Regeneration of squamous cells was observed in all inserted mucosal tissues. The other entire lumen surface without the mucosal lining was covered with connective tissue.

Example 5 Angiographic Evaluation

Angiography using lipiodol was performed to observe the angiogenesis of the internal mucosa and airway prosthesis from the long-term vascular system. Experimental dogs were anesthetized by the method mentioned in Example 2. The dogs were reopened and resected from the center to remove the longus surrounding the airway implant from the spleen to observe the artery of the right upper reticulum. 16 gage IV cannula was used for this observation. 20 ml Lipiodol was injected very slowly. Finally, long-term and inserted airway prostheses were resected, and the transplanted mucosal tissue showed flushing of normal tone. Angiogenesis of the resected prosthesis was measured using mammography.

3 is an X-ray photograph showing the growth of blood vessels into the mucosal cells transplanted from the blood vessels of the long-term, Figure 4 is a tissue photograph showing that the transplanted mucosal cells are growing well. Angiogenesis was found in the entire airway prosthesis, especially in the middle of the airway prosthesis. The part was where the mucosa was inserted. The results demonstrate the formation of new blood vessels into the implanted mucosa.

The present invention facilitates the adhesion between the airway prosthesis and the internal tissue of the body and maintains the survival and function of the airway by using an airway prosthesis implanted and applied by an adhesive in the case of airway resection. Allow the prosthesis to act as an airway.

Claims (10)

(a) a cylindrical tube comprising a cylindrical tube and at least two rings to reinforce the tube; and (b) an airway prosthesis comprising autograft mucosa tissue adhered to the inner surface of the cylindrical tube with an adhesive. The airway prosthesis of claim 1 wherein the adhesive is a biodegradable material. The airway prosthesis of claim 1, wherein the adhesive is gelatin. The airway prosthesis of claim 1, wherein the adhesive layer bonded with the adhesive has a thickness of 0.8 to 1.2 mm. The adhesive coated airway prosthesis of claim 1 wherein the cylindrical tube is a proline mesh and the ring is a polypropylene ring. The airway prosthesis of claim 1 wherein the adhesive between said rings is 4-6 mm apart. 2. The airway prosthesis of claim 1 wherein the size of the ring is between 0.3 and 1.1 mm thick and between 0.3 and 1.1 mm wide. The adhesive coated airway prosthesis of claim 1 wherein the adhesive-applied airway prosthesis has a diameter of 25 to 45 mm. Adhesives containing only gelatin used to bond prostheses with internal tissues. The adhesive of claim 9 wherein the prosthesis is an airway prosthesis and the body internal tissue is long-term.