Absorbable Triphasic Hernial Meshes

描述（申请人提供）：疝修补是普通外科中最常见的手术，其中合成补片常用来修复腹部缺损。常用的网片由不可吸收的聚合物组成，如聚丙烯、聚对苯二甲酸乙二醇酯或聚四氟乙烯。最近建立的修改这些网，以提高他们的生物力学相容性和愈合过程包括与可吸收的乙醇共聚酯或聚二氧烷的组合。然而，不可吸收的网片及其与可吸收成分的组合确实存在明显的不良特征，部分原因是它们无法(1)允许逐渐将负荷转移到愈合组织以协助加速伤口愈合；(2)防止或减少粘连的形成在手术部位，由于其几乎生物惰性的表面；(3)显示逐渐减少的模量，以适应愈合手术部位的生物力学；(4)防止或尽量减少其预期功能性能结束后挤压和感染事件的可能性。这种不足促使当代外科医生和生物工程师强调需要能够提供(1)初始高爆裂强度和刚度（或弯曲模量）的新网；(2)可测量的保持/破裂强度至少8周，这在临床上与老年患者受损组织伤口的疝修复有关；(3)在组织愈合期间和愈合后不久，逐渐降低保持/破裂强度，将负荷逐渐转移到周围组织，这有助于愈合过程和形成强壮、有组织的新组织；(4)动态再生生物活性表面，以减少感染和粘连形成的发生率；(5)表现出导致手术部位几乎全部质量损失的质量损失曲线。这为进行拟议的第一阶段研究提供了动力。因此，第一阶段的目标是确定开发可吸收的三相疝网的可行性，该网状物由两种不同的纤维成分和涂层组成，以在关键愈合过程中和之后逐渐改变生物力学剖面和生化相容的组织界面。第一阶段计划包括(1)合成、表征和转化成相对快速和慢速吸收聚合物的多长丝；(2)将两种纱线编织成经编候选网目；(3)一种可吸收的含氮共聚聚酯的合成和表征及其用于涂覆候选网格；(4)涂层网的灭菌，体外评价其初始力学性能和在降解环境中孵育的效果；(5)完成选定候选物的有限动物研究，并确定两种最有希望用于规划II期研究的网格。这将需要全面的体外和体内评估，选择最终和备用候选物，完成聚合物和网状物的开发，扩大研究和启动临床前研究。

DESCRIPTION (provided by applicant): Hernial repair is the most frequent operation in general surgery for which synthetic meshes are commonly used in repairing abdominal defects. Frequently used meshes consist of non-absorbable polymers such as polypropylene, polyethylene terephthalate, or polytetrafluoroethylene. Recently established modifications of these meshes to improve them biomechanical compatibility and the healing process include combination with absorbable glycolide copolyesters or polydioxane. However, the non-absorbable meshes and their combinations with absorbable components do suffer distinctly from undesirable features associated, in part, with their inability to (1) allow gradual load transfer to healing tissues to assist in accelerating wound- healing; (2) prevent or minimize adhesion formation at the surgical site due to their practically bioinert surfaces; (3) display, incrementally, decreasing modulus to accommodate, favorably, the biomechanics of healing surgical sites; and (4) prevent or minimize the likelihood of extrusion and incidents of infection following the conclusion of their intended functional performance. Such inadequacy prompted contemporary surgeons and bioengineers to stress the need for new meshes capable of providing (1) an initially high burst strength and stiffness (or flexural modulus); (2) measurable holding/bursting strength for at least eight weeks-this is clinically relevant to hernial repair of compromised tissue wounds as in geriatric patients; (3) incrementally decreasing holding/bursting strength during and shortly after the tissue healing to transfer the load, gradually, to surrounding tissues-this is to aid the healing process and formation of strong, organized new tissues; (4) dynamically regenerating bioactive surfaces to minimize the incidence of infection and adhesion formation; and (5) exhibit mass loss profiles leading to practically total mass loss at the surgical site. This provided the incentive to pursue the proposed Phase I study. Accordingly, Phase I objective is to determine the feasibility of developing absorbable triphasic hernial meshes comprising two different fibrous components and a coating to provide, incrementally, changing biomechanical profiles and biochemically compatible tissue-interfacing surfaces during and following the critical healing process. And Phase I plans entail (1) synthesis, characterization and conversion to multifilament yarn of relatively fast- and slow-absorbing polymers; (2) construction of the two yarns into warp-knitted mesh candidates; (3) synthesis and characterization of an absorbable, nitrogenous copolyester and its use to coat the candidate meshes; (4) sterilization of coated meshes and in vitro evaluation of their initial mechanical properties and effect of incubation in degrading environments; and (5) completion of a limited animal study on selected candidates and identification of two most promising meshes for use in planning Phase II study. This will entail comprehensive in vitro and in vivo evaluation, selection of a final and back-up candidates, completion of polymer and mesh development, and scale-up studies and initiation of preclinical studies. PUBLIC HEALTH RELEVANCE: Development of a novel triphasic, absorbable mesh, exhibiting a three-step mass loss profile for hernial repair, using a relatively fast- and slow-absorbing multifilament yarn constructed in a new warp-knitted form and coated with a fast-absorbing, lubricious absorbable polyester, will provide the surgeon with an exceptionally effective tool for repairing different forms of hernia without contending with the established clinical drawbacks of single-component, non-absorbable, and bicomponent, partially absorbable commercial meshes.