Biocompatibility Assessments of Surgical sutures: The Guinea Pig Maximization Test

Abstract

Surgical suture is a medical device used to hold body tissues together after an injury or surgery. Application generally involves using a needle with an attached length of thread as evaluated for the potential to cause delayed skin contact sensitization in a Closed-patch test. This study was conducted base on the requirements of ISO 10993-10: Biological Evaluation of Medical Devices-Part 10: Tests for Irritation and Skin Sensitization. The guinea pig maximization test (GPMT) is made of the potential of the material under test to produce skin sensitization. The polar and nonpolar extracts were prepared by using saline solution and olive oil, respectively, after sinking the materials tested (2.0 g) in 10 ml of the corresponding liquid. Incubation was carried out at the temperature of 37 °C for 72 h. The saline solution and pure olive oil were used as negative control samples and were incubated under the same conditions as above. The guinea pig maximization test (GPMT) consist of intradermal induction phase, topical induction patches and challenge phase. Following a intradermal induction phase, The test item extract with polar and non polar solvent were injected in clipping area of each animal in test group and control group, respectively. Following a challenge phase, the test group and control group were challenged with the test item. No evidence of sensitization was observed. Individual results of skin scoring for the induction phase and the challenge phase is 0.0. Keyword : Surgical suture,Intravenous reactivity test. Introduction Polymeric materials have dramatically influenced our day to day life. They find potential in various fields like food packaging, automobiles, water purification etc. [1-3] Application of polymeric biomaterials in medicine has been a thrust area of research owing to the exceptional and superior properties they exhibit. [4] The increased use of polymeric biomaterials in the form of surgical implants, sutures and scaffolds for biomedical applications. [5] Tangthong Jiraporn et al /International Journal of PharmTech Research, 2019,12(1): 90-95. DOI: http://dx.doi.org/10.20902/IJPTR.2019.120112 International Journal of PharmTech Research CODEN (USA): IJPRIF, ISSN: 0974-4304, ISSN(Online): 2455-9563 Vol.12, No.01, pp 90-95, 2019 Tangthong Jiraporn et al /International Journal of PharmTech Research, 2019,12(1): 90-95. 91 Surgical suture is a medical device used to hold body tissues together after an injury or surgery. Application generally involves using a needle with an attached length of thread. A number of different shapes, sizes, and thread materials have been developed over its millennia of history. Surgeons, physicians, dentists, podiatrists, eye doctors, registered nurses and other trained nursing personnel, medics, and clinical pharmacists typically engage in suturing. Surgical knots are used to secure the sutures. [6] The primary purpose of suture is to hold apposing tissues together to facilitate and hasten healing process with minimal or no scar formation following an injury or surgical procedure. [7] A variety of materials such as gold, silver, iron and steel wires, dried animal gut, animal hair (e.g. horse hair), silk, tree bark and plant fiber (e.g. linen, cotton) were used as suture materials in the past, while some of them are still use. The recent has witnessed the use of various synthetic biomaterials such as polydioxanone, poly(lactic-co-glycolic acid) as suture materials. [8] To minimize any potential hazards to the patients, it is essential that biocompatibility assessments be conducted for surgical suture made from Polyglycolide-Co-L-Lactide that are used in medical devices. The common tests are used to measure biocompatibility: ISO10993-10, Biological Evaluation of Medical Devices (2010). [9] Animals and Husbandry The albino Dunkin Hartley guinea pig has been used for sensitization studies. Repeated patching of the test item to fur clipped intact skin will be employed. Topical applications are related to the human exposure route and permit the evaluation of dermal contact and/or absorption of potential sensitization. Reactions directly under the topical application site can be observed. Animals and husbandry were conducted based on the test guidance of The International Organization for Standardization 10993-2, Biological Evaluation of Medical Devices-Part 2: Animal Welfare Requirement, 2006 [10] , The International Organization for Standardization 10993-10, Biological evaluation of medical devices Part 10 Test for irritation and delayed type hypersensitivity, 2010 [9] and Guidelines of “Guide for the care and use of laboratory animals” (Institute of laboratory animal resources, National academic press 2011; NIH publication number #85-23, revised 2011). The healthy young guinea pig of body weight in range 300 500 g were obtained from Office of Laboratory Animal Production, NLAC, Mahidol University, Thailand. The animals were kept under standard conditions 12:12 (light : dark cycles) at 22±3 0C and 30-70% relative humidity. The animals were housed individually in cages. The animals were fed with feed and chlorinated water ad libitum. All the animals were acclimatized for 5 days prior to the study. The study was approved by National Laboratory Animal Center Animal Care and Use Committee (NLAC-ACUC), Mahidol University; Thailand. Preparation of the test material extracts The surgical suture (Polyglycolide-Co-L-Lactide) and control item preparation was conducted based on the test guidance of the International Organization for Standardization 10993-12, Biological Evaluation of Medical Devices – Part 12: Sample Preparation and Reference Materials, 2007. [11] Polar solvent (Physiological saline) and Non polar solvent (olive oil) were used as a control item. Two grams of the surgical suture (Polyglycolide-Co-L-Lactide) was extracted in Polar solvent and Non polar solvent. The solutions were performed in a water bath at 37oC for 72 hours. Polar solvent and non polar solvent which had no contact with the surgical suture were use as negative control and were incubated under the same conditions as above. The extracts were used within 4 hours to perform the test procedure. [11] Intradermal Induction phase Fur on the back of each animal was clipped with an electric clipper 16 – 24 hours prior to exposure. On the day of exposure, the clipped area was separated to 2 sites on each animal. The surgical suture (Polyglycolide-Co-L-Lactide) extraction and control item were intracutaneous (Intradermal) applied to the test sites and control sites respectively. Tangthong Jiraporn et al /International Journal of PharmTech Research, 2019,12(1): 90-95. 92 The animals in test group and control group were injected with 0.1 ml intradermal in the clipped area. The injection sites (A, B and C) as Site A: A 50:50 volume ratio stable emulsion of Freund’s complete adjuvant mixed with the solvent and use 0.9% sodium chloride for water soluble material. Site B: The test animals were injected with test item extraction and control animals were injected with the solvent alone. Site C: The test animals were injected with test item extraction diluted in 50:50 volume ratio stable emulsion of Freund’s complete adjuvant and the solvent. The control animals were injected with an emulsion of blank liquid with adjuvant. Topical Induction phase At 7 days after completion of intradermal induction phase, the fur of all test and control group were clipped with an electric clipper. All test and control animals were administrated the test item by topical application to the intrascapular region of each animals, using a patch approximately. The 10% sodium dodecyl sulfate was massaged in to skin 24+2 hours before the topical induction. The concentration for site B was selected to applied to the intrascapular region. The patchs were removed after 48+1 hours.