同种异体肌腱免疫原性相关的基础研究进展

Advances in basic research related to immunogenicity of allogeneic tendon

肌腱移植是肌腱损伤后进行重建的主要治疗手段之一，常用的移植材料包括：自体肌腱、同种异体肌腱、异种肌腱、人工肌腱以及组织工程化肌腱等。同种异体肌腱因其具有供体来源丰富、无供区并发症及手术时间较短等优势而越来越多地被临床使用。然而，同种异体肌腱移植往往也增加免疫排斥反应、疾病传播及骨一腱愈合延迟等风险。针对以上缺陷大量的研究已报道不同的处理手段，目前常用于降低肌腱免疫原性的加工方式可分为：物理法（冷冻干燥法、深低温冷冻法及玻璃化冷冻保存法等）及化学试剂浸泡培养法（脱氧鸟苷培养液、磷酸三丁酯、三氯甲烷／甲醇、十二烷基硫酸钠、95％纯度酒精及Triton X-100等）。在物理冷冻法中，冷冻干燥能更加有效地去除肌腱的免疫原性，但也易导致肌腱的力学、结构及组织学等特性受到不同程度的损伤，尤其当该方法与辐照灭菌等工艺联合使用时更易导致肌腱的损伤。而深低温冷冻对肌腱的力学及组织学特性的损伤较为轻微，该种方法目前在临床及科研中最为常用。玻璃化保存法则在保护肌腱力学特性及细胞活性等方面具有独特的优势，能保留与新鲜肌腱相似的力学特性。然而，该种方法所涉及复杂的制备程序、较高的费用及冷冻保护剂的细胞毒性作用等因素一直制约着其在实际生产中的应用。不同的化学去细胞方式在消除肌腱免疫原性方面也存在各自的优缺点，为达到更加彻底地去除细胞成分同时最大程度地保留肌腱的结构及力学完整性，往往需要严格地控制去细胞剂的浓度和处理时间，必要时需联合使用多种方法共同处理。

Tendon transplantation is one of the most commonly used procedures for patients with injured tendons. The materials used for tendon transplantation include the tendon autograft, tendon allograft, xenogenic tendon and artificial ligament.Of these, the allogeneic tendon has become more and more widely accepted because of the abundant donor source, absence of complications at donor sites and reduced operation time. However, it would meanwhile increase the risks of immunological rejection, disease transmission and delayed tendon-bone integration. A lot of studies have reported many processing technics to solve thementioned drawbacks of tendon allograft. Regarding to the immunological rejection, many approaches have been proposed including physical freezing （such as deep freezing, freeze drying and cryopreservation using the vitrification method） and chemical decellularization （such as deoxyguanosine culture solution, trinbutyl phosphate, chloroform / methyl alcohol, sodium dodecyl sulfate, 95% ethanol and Triton X-100）. Among the physical freezing methods, freeze-drying could remove the immunogenicity of tendon more effectively, but it also tends to cause damage to the mechanics, structure and histology of the tendon. And it is more likely to cause damage to tendon especially when the method is used in combination with irradiation sterilization. Deep freezing has less damage to the mechanical and histological characteristics of tendon, and this method is currently the mostcommonly used in clinical and scientific research. The vitrification preservation method has unique advantages in protecting thetendon mechanical properties and cell activity. It retains similar mechanical properties to fresh tendons. However, the complicated preparation procedures involved in this method, the high cost and the cytotoxicity of the cryoprotectant have always restrictedits application in actual production. Different chemical deeellularization methods have their own advantages and disadvantages when used to reduce the immunogenicity of tendons. In order to achieve more thorough removal of cellular components in tendonswhile maximally retaining the structural and mechanical integrity of tendons, strict control on the concentration of the decellularizing agent and the treatment time is often required.