Study on absorbable suture of biomaterials
HE Liping，LI Wenping，LUO Guoliang,et al.
(College of Animal Science and Technology,HuNan Agricultural University,Changsha 410128,China)
Abstract： Absorbable suture has been widely used in medicine and veterinary medicine,which is one of the most active do mains on biomedicine macromolecule research. This paper gave a general review about their absorbability,degradation and research status.
Key words: biomaterial;
surgical suture; biological degradation
Medical absorbable
surgical suture is a kind of biological materials, it is mainly used in general surgery and plastic surgery need to suture surgery. It can provide the body with temporary bracket or barrier, can through the absorption and degradation to avoid rejection, non-infectious inflammation in the body and other adverse effects, and reduce the chances of the second operation [1], and so on medicine and animal medicine, it has obvious advantages compared with other surgical sutures, widely clinical application, is a highly development potential of absorbable implant material. With the development of science and technology, people more and more research on absorbable
surgical sutures. Many scholars think [2], the ideal surgical sutures should satisfy the following conditions: (1) can be a thorough disinfection sterilization; (2) has certain mechanical properties, such as proper mechanical strength, about 20% of the extension, has certain flexibility and elastic recovery, have certain wet strength and friction coefficient; (3) when suture knot, convenient operation, concludes the knot after good performance; (4) the suture line intensity is constant within a certain time in the body; (5) adaptability to human tissue, not because of foreign body reaction and inflammation; (6) the product quality is stable and reliable, easy, cheap.
The absorbable sutures can be divided into natural absorbable sutures and synthetic absorbable sutures. The former mainly have gut, collagen can be absorbed sutures, chitin and chitosan absorbable surgical suture line, etc., which has poly glycolide sutures, poly lactic acid can be absorbed sutures, get together on two heterocyclic oxygen already ketone suture line, etc.
1 natural absorbable sutures
1.1 gut in all natural absorbable sutures, gut is one of the most traditional, starting from the earliest medical records, the surgery that has been used in the gut, it is taken from the gut mucosa in the submucosa. In the body of the degradation and absorption give energy to macrophages activity depends mainly on the existence of the cathepsin. Gut suture materials are still commonly, because its source is wide and relatively simple production process, low cost. But it has poor flexibility, response, infection of digestive juices and tensile strength under the environment of fast loss of faults. To solve these shortcomings, people made laced with crosslinking agent chromium and chromic catgut made of iodine iodine gut, the tensile strength and extension of the former can increase the gut to maintain stress time, which has the potential to reduce incision infection rate, but both cannot completely avoid the disadvantage of the gut [2].
1.2 collagen fiber absorbable sutures in collagen from animal bones, fascia, soaking boiling, extracted multi-channel processes such as hydrolysis, and then through twisting and the effect of crosslinking agent and made. Collagen surgical sutures, lies in the nature of the collagen [3, 4]. Stress - strain test showed that the natural collagen show the elastic and viscoelastic states the mechanical behavior of two phases; And collagen antigenicity is quite low, have natural biodegradable properties, and can promote the cell growth. Collagen these properties make it can be successfully used for the preparation of medical surgical sutures. Absorbable sutures made with collagen fiber has the following advantages: (1) good plasticity, can be processed into various shapes; (2) into a fiber performance is good, after extrusion forming by tensile strength to some degree; (3) the products have good histocompatibility, no bad reaction after implantation in the human body, non-toxic, can be absorbed by human body. But, according to a report in the Zheng Shufen etc. [5] the collagen has the defects of the absorption rate is easy to change. WenYongTang collagen absorbable sutures are investigated in [6], such as production, he according to the principle of combination of glutaraldehyde and collagen protein, using it as a crosslinking agent, and to explore the surgical sutures made the intensity and the concentration of glutaraldehyde and glutaraldehyde and collagen reaction pH, time, relationship, this provides reference for later people to develop new surgical sutures. Collagen absorption rate is related to its strength, to get a higher intensity of sutures, since 1990, Guo Zhenyou etc. [7] started to mixed collagen and amino glucan and other natural materials as raw material to make a suture line, he had developed at the suture line not only retains the original collagen suture the good plasticity, fibre performance is good, good histocompatibility, into non-toxic characteristics, its strength is greatly higher than that of collagen suture line, knot strength also reach and exceed target set by the United States pharmacopoeia.
1.3 of chitin, chitosan can be absorbed sutures in chitin as raw material to produce absorbable sutures in the 1970 s, Japan studies in the field in the world, famous "sonjica company has several patents and products come out [8]. Domestic related research began in the 90 s. Currently, chitin suture line has a mature production technology, generally USES the wet spinning process, the raw material is high purity of chitin powder, more commonly used six fluoride solvent acetone, six fluorine isopropyl alcohol, trichloroacetic acid, etc. Concreting by choosing different solvents, and improve the spinning and processing technology, the preparation of a variety of models and can meet the different needs of absorbable chitin suture.
According to the test of scholars [9] chitin suture has many unique advantages: (1) the body well tolerated; (2) has certain antibacterial anti-inflammatory effects, can promote wound healing, scar small; (3) the strength and flexibility in the moderate, surface friction coefficient is small, easy to suture and knot; (4) for regular disinfection, dyeing, anti-corrosion and other special processing; (5) absorption evenly after the intensity attenuation rate is moderate, can satisfy the requirement of wound healing process of sutures strength; (6) the wide raw material sources, simple processing, low cost. Goosen etc. [10] the study showed that chitin suture of digestive enzymes, infected tissue and urine tolerance is better than gut and PGA. Hou Chunlin etc. [11] also by testing animals fully shows that the performance of chitin suture is superior to gut. But at the moment, chitin suture in clinic is not widespread use, the main problem is that the tensile strength, there is still a gap compared with the PGA class sutures, still cannot meet the needs of high strength and suture; And under the condition of the gastric juice acidity such as rapid strength loss; Animal experiments show that the use of chitin suture in the middle of the wound healing will appear unexplained mild inflammation. To solve the problems in actual use, has been reported literature [12] the preparation of chitin derivatives suture line, at the same time, using some of the new spinning technology, such as increasing chitin strength of liquid crystal spinning, etc., can get better effect.
Su Xiurong etc. [13] reported extract preparation of chitosan from shrimp crab shells medical surgical absorbable surgical sutures, and the suture with gut suture experiment has been carried out in mice, by tissue slice, scanning electron microscope observation, proved that the absorption of the surgical suture line of chitosan in the body is superior to the gut; And through the experiment proves that the surgical suture line of chitosan is non-toxic, harmless, without any side effects, easy to knot, easily absorbed by the body of the medicinal materials.
Humans found chitin and chitosan have been 100 years of history, but it used to make medical sutures or nearly 30 years. From the existing research results of chitin and chitosan have good application prospects. But currently in clinical use of chitin and chitosan implant materials are very limited, the main reason is facing three major difficulties: (1) the limitation of preparation technology, besides its in certain solvents, currently there is no more effective processing methods; (2) products in total after implantation inevitably brings the different response of the organism that for unknown reasons; (3) the degradation rate of products is influenced by many factors (mainly), out of control.
Since then, there is a kind of brown seaweed as raw material of seaweed fiber, the algae salt is made from roses uronic acid dew and long chain of uronic acid copolymer, as a fine serrated belt, the molecule structure of alginate fiber provides good performance, has the high absorbent, check blood and tissue tropism etc. [14]. Properties of the fiber and the development and utilization of seaweed are under study.
To sum up, in the natural absorbable sutures, because gut production technology is relatively simple, and used for a long time, although there are many shortcomings, but now, especially in our country, the use of the gut proportion occupy the bigger market still; And collagen fiber absorbable sutures, although low antigenicity, but absorb period length of the work to be thorough; And at present, chitin, chitosan research is a hot spot, its production technology is mature, and has the advantages of it fixed, therefore its research prospect is broad. The author thinks that, if the chitin, chitosan to processed into better sutures, its production process and antigenicity, degradation rate must be more in-depth research.
2 synthetic absorbable sutures
Nearly two hundred and thirty years, according to people in order to get a higher flexibility, higher strength, and to meet different surgical requirements needed for the different degradation performance of new sutures, people made a further research, obtained has the excellent properties of absorbable surgical sutures. These sutures overcomes the gut and collagen line faults, high fracture strength, tissue reaction and the absorption effect is good wait for an advantage, that result in the people's great attention. At present, mainly has the following several synthetic suture line approved by the FDA, can be listed, so they are more widely research and application.
2.1 gather glycolide (poly (glycolic acid) a variety of commercialization of suture line this is the earliest. Is relatively easy to hydrolysis and degradation products glycolic acid is the intermediate metabolism of the body. Making it in the development of absorbable sutures are preferred in the study, and in 1962 by the United States American Cyanamial company development, commodity called Dexon. Du Chun foot [15], its tensile strength than bowel line, cotton thread, similar to polyester line, but the response is smaller than it. Dexon absorbed time to start with the implanted tissue of different and different, generally between 30 ~ 60 days is absorbed. Reports [16] that Dexon mechanical strength in the wastage of the body faster, degradation rate is big, usually only suitable for 2 ~ 4 weeks of surgery. The suture line has the uniformity, stability and inertia, non-toxic, no antigenicity, no carcinogenicity, resistant to acid stomach enzymes and infection, minimal tissue reaction. In recent 10 years, as absorbable biomaterials in vivo, poly glycolide molecular engineering progress is mainly manifested in the following three aspects: (1) by mu oxygen bridge double metal ring opening polymerization of alkyl oxide catalyst activity, the successful synthesis of the poly (glycolic acid ester/polylactic acid ester (PGA/PLA) embedded copolymer, thus expanding the scope of this kind of material; (2) materials to improve the flexibility and suitable for manufacture monofilament surgical sutures; (3) development in PGA, PLA, poly (ethylene oxide (PEO) as soft segment of the block copolymer.
2.2 poly lactic acid (poly (lactide) absorbable sutures polylactic acid (PLA) is a kind of good biocompatible and biodegradable polymer, approved by the us food and drug administration (FDA) can be used as medical sutures. Li Xiaogong etc. [17] reported: PLA in the body metabolism is the final product of CO2 and H2O, the intermediate product of lactic acid and normal glucose metabolism in vivo, so it couldn't have gathered in vital organs. Polylactide and its copolymers as surgical sutures, due to its biodegradability, automatically degradation and absorption after wound healing, without secondary surgery, so favored by the doctor [18]. In 1975, PLGA (LA/GA = 90/10) began as a surgical suture line on the market. At present, the absorbable surgical suture in production of polylactide and its copolymers of study, there are still many problems still need to solve. Among them, looking for a suitable catalyst is an important topic of the research. [19] In recent years, studies have focused on the following aspects: (1) increase mechanical strength of sutures, synthesis of high molecular weight PLA, improve the stitching process; (2) the optical activity of polymer synthesis. Semicrystalline PDLA and PLLA than amorphous PDLLA has high mechanical strength, large tensile ratio and low shrinkage [20], more suitable for surgical suture; (3) the multi-functional sutures. The suture line, for example, adding anti-inflammatory drug to inhibit local inflammation and foreign body rejection. At the same time, how to make polymer degradation rate and wound healing time match better, how the sutures adding anti-inflammatory drug to inhibit local inflammation and foreign body rejection of work remains to be further [21].
2.3 poly 2 oxygen heterocycle already ketone sutures after this matter is Dexon and polylactic acid acetic acid of another kind of absorbable suture, referred to as "PDS. Ether chain due to its molecular chain, the molecular chain of flexible, so it can be made into different sizes of monofilament sutures. PDS tissue reaction induced by small, monofilament tensile strength than polypropylene, polyamide and PDS in biological tissues strength retention, stitching for healing the wound is particularly useful for a longer time [15], but for the wound heal faster, sutures when losing support function becomes encumbrance of the organization.
Was developed in the mid - 80 - s, ETHICON company for oxygen heterocycle already ketone and glycolide sutures crystal block copolymer, the suture line not only possesses the advantages of monofilament suture line structure, and shorten the suture absorption, increased flexibility, to expand the use of poly for the dioxolane ring already ketone. Its soft and absorbent were superior to the dioxolane ring already ketone homopolymer. Some people think that [22], so far, it is the best absorbable sutures. But look from literature [23] and block copolymerization difficult operation, process complex, is not easy to industrial production. Improved block copolymerization, therefore, operating technology development, will greatly make up for the inadequacy of ring already ketone sutures for oxygen, make its become outstanding in the absorbable suture.
2.4 glycolide - sanya methyl carbonate copolymer sutures by glycolide and carbonic acid trimethyl made by copolymerization of surgical suture has been developed in abroad, also called Maxon surgical sutures. It is made of 32.5% of the sanya base carbonate and glycolide polymerization, can be made into monofilament sutures [23]. The sutures is higher than pp and nylon nodules intensity peace straight tensile strength and its response to a small. Maxon in the body, according to the [24] blayne intensity decreased slowly, in 28 days, Maxon can still maintain the original strength of 59%, and can be fully absorbed in 6 ~ 7 months. In order to improve the operating performance of sutures, reduce tissue frictional resistance and so on, can the suture surface coating and impregnation, the sutures in the human body the absorption speed and not significantly affect the tensile strength retention. [25]
Above several is currently listed has been approved by the FDA sutures, now to experiment and to approve and polyester amide, poly ethylene propylene ester, etc.
Anyhow, synthetic sutures research will promote the development of absorbable sutures to study. Although these synthetic materials is better than that of natural absorbable sutures, because they are in the body through the hydrolytic degradation become non-toxic products, and eventually absorbed by the organization. But because of the synthetic technology is higher, and there are their respective shortcomings respectively (described above), its application is limited, especially in our country, its ability to mass production is still very low. But with the development of science and technology, especially the rapid development of biotechnology, believe their faults can be solved, so as to make them more widely application in clinic.
3 the absorbable surgical suture research status in our country
In the research has been started in our country, the research work mainly focused on poly glycolide, material such as polylactic acid synthesis and in vitro degradation and animal experiment. But so far, most of these research work only at the laboratory stage, there are many key technologies need to be resolved. At present domestic hospitals use mainly by gut. For the development and utilization of collagen fibers, has already started in our country, there are mass production, but there are still many problems unsolved, such as collagen fiber premature suture absorption shortcomings. Source of chitosan, chitin suture materials, the author thinks, our country coast is longer, shrimp, crab and other resources rich in chitin chitin resources, used for processing into
surgical sutures and other biological products, has a great advantage, but due to the limitation of production technology, the development and utilization of chitin in China also is not very perfect. And the study of synthetic absorbable sutures, although some reports,21,22 [19], but the actual production of the quality of the product compared with foreign advanced level, there is still a certain gap, mainly is the quality is not stable, high grade of absorbable suture line can't production, so the use of synthetic absorbable surgical suture is limited by a lot of. Investigate its reason, main is facing three major difficulties in the study: (1) the limitation of preparation technology, products mechanical performance is not satisfied; (2) more advanced absorbable sutures are expensive; (3) to improve the strength of the polymer and solve the problem of late implant reaction and complications must be in-depth study. In order to solve the above problem, in our country vigorously in the research is very necessary. At present, we can use all kinds of methods, such as derivatives or consider using natural biological materials for the chemical modification and surface treatment to solving the problems of antigenicity. In our country, medical absorbable
surgical suture line of research are increasingly brought to the attention of the general research scholars, its research field is also growing, people are now looking for new high performance materials, improve production technology, in order to make their research more and more closer to the world's advanced level. To speed up the related research and development work has important economic and social benefits. With the development of science and technology and the constantly find and application of new materials, medical absorbable sutures will become a full of vitality and hope research field.
