Endometrial mesenchymal stem cells as a cell based therapy for pelvic organ prolapse

Pelvic organ prolapse(POP) occurs when the pelvic organs(bladder, bowel or uterus) herniate into the vagina, causing incontinence, voiding, bowel and sexual dysfunction, negatively impacting upon a woman's quality of life. POP affects 25% of all women and results from childbirth injury. For 19% of all women, surgical reconstructive surgery is required for treatment, often augmented with surgical mesh. The surgical treatment fails in up to 30% of cases or results in adverse effects, such as pain and mesh erosion into the bladder, bowel or vagina. Due to these complications the Food and Drug Administration cautioned against the use of vaginal mesh and several major brands have been recently been withdrawn from market. In this review we will discuss new cell-based approaches being developed for the treatment of POP. Several cell types have been investigated in animal models, including a new source of mesenchymal stem/stromal cells(MSC) derived from human endometrium. The unique characteristics of endometrial MSC, methods for their isolation and purification and steps towards their development for good manufacturing practice production will be described. Animal models that could be used to examine the potential for this approach will also be discussed as will a rodent model showing promise in developing an endometrial MSC-based therapy for POP. The development of a preclinical large animal model for assessing tissue engineering constructs for treating POP will also be mentioned.     

子宫托对阴道微生态的影响以及应用雌激素的作用

通常将阴道前后壁、膀胱或直肠等盆腔脏器突入阴道内,称为盆腔脏器脱垂,常发生于老年女性。盆腔脏器脱垂及其引起的排尿相关症状严重影响患者的生活质量。目前临床上治疗盆腔脏器脱垂最常用的方法为佩戴子宫托。子宫托治疗盆腔脏器脱垂已有久远的历史。使用子宫托可明显改善盆腔脏器脱垂患者的临床症状,提高患者的生活质量。然而研究显示,对于机体而言,阴道内放置子宫托可在一定程度上影响阴道微生态环境平衡,从而使佩戴子宫托患者的细菌性阴道病患病率增加4.37倍。同时使用雌激素可明显减少由使用子宫托引起的阴道微环境改变、出血、溃疡等症状的发生。现就子宫托对阴道微生态的影响以及应用雌激素的作用做一简要综述。     

生物补片的临床应用进展

人体组织损伤再生修复一直是临床面临的难题,近年来,随着细胞生物学和组织工程技术的发展,生物补片作为一种新兴的创伤修复材料的出现为人们带来了曙光,生物补片是天然真皮基质经脱细胞处理而形成的三维支架结构,作为生物工程支架可通过空间诱导和组织替代作用修复组织缺损,由于其去除了引起宿主免疫排斥反应的所有成分,具有良好的组织相容性,现已广泛应用于临床各领域的缺损组织修复,并取得了良好的应用前景。生物补片在疝外科的应用较为成熟,尤其对合并感染的情况治疗效果颇佳,在小儿疝外科的应用效果亦较好;在治疗肛瘘方面,生物补片的应用,改变了传统的治疗理念,实现了肛门括约肌的功能性重建;在整形医学领域中烧伤、隆鼻及隆乳方面的应用,利用生物补片再生的机制,使组织恢复原貌更具美学价值;在妇产科方面,盆底解剖及功能重建方面前景广阔。然而在骨科中的骨组织及韧带再生,泌尿外科中膀胱、输尿管及阴茎的重建,心血管邻域中修复心脏瓣膜治疗先天性心脏病方面的应用虽取得一定的成果但整体仍处于实验探索阶段,仍需继续研究拓展;生物补片虽然已形成商品化但因其价格昂贵等因素阻碍了临床广泛应用。本文就近年来生物补片在外科领域的应用研究进展作一综述。     

Expression of estrogen receptors in the pelvic floor of pre- and post-menopausal women presenting pelvic organ prolapse

The precise role of estrogen in the pathogenesis of pelvic organ prolapse (POP) is still unclear, while the results concerning the effect of selective estrogen receptor modulators on pelvic organ prolapse are contradictory. Our aim was to test whether alteration in the expression of estrogen receptors in the pelvic floor of pre- and post-menopausal women is related to genital prolapse status. The mRNA levels of ERα and ERβ in 60 biopsy specimens were measured. Significantly higher expression of ERα and higher ERα/ERβ ratio were demonstrated in post-menopausal women compared to pre-menopausal women. Higher expression of ERα and higher ERα/ERβ ratio were detected in all studied groups with POP, thus it did not reach significance in the post-menopausal group. Pre-menopausal and post-menopausal women presenting pelvic organ prolapse had no difference in the ERα expression. Our preliminary study may indicate that pelvic organ prolapse is associated with higher expression of ERα/ERβ in the pelvic floor of both pre- and post-menopausal women; thus not reaching statistical significance in the post-menopausal women was probably due to the group's size. We believe that the inevitable changes in the estrogen receptor expression over women's different lifetimes may affect the risk of genital prolapse progression, and might contribute to the further search for appropriate selective estrogen receptor modulators as a treatment for women with pelvic organ prolapse.     

生物反馈电刺激联合Kegel训练对产后盆底功能障碍性疾病患者盆底功能电生理指标和生活质量的影响

目的:观察生物反馈电刺激联合Kegel训练对产后盆底功能障碍性疾病(PFD)患者盆底功能电生理指标和生活质量的影响。方法:研究对象为2018年3月~2020年12月我院收治的80例产后PFD患者。采用双色球随机分组法将患者分为对照组(n=40)和研究组(n=40)。对照组给予Kegel训练,研究组给予生物反馈电刺激联合Kegel训练,两组均治疗8周。对比两组治疗8周后的疗效和尿失禁、盆底器官脱垂程度的改善情况。对比两组治疗前、治疗8周后的盆底功能电生理指标、日常生活质量和性生活质量。结果:治疗8周后,研究组的临床总有效率较对照组高(P<0.05)。治疗8周后,研究组I类肌纤维疲劳度、Ⅱ类肌纤维疲劳度、快肌最大肌电值及阴道动态压力均优于对照组(P<0.05)。研究组治疗8周后尿失禁、盆底器官脱垂程度的改善情况优于对照组(P<0.05)。治疗8周后,研究组盆底功能影响问卷简表(PIFQ-7)评分、盆腔器官脱垂-尿失禁性功能问卷(PISQ-12)评分均低于对照组(P<0.05)。结论:产后PFD患者采用生物反馈电刺激联合Kegel训练治疗疗效明确,可促进尿失禁、盆底器官脱垂程度情况及盆底功能改善,提高患者日常生活质量和性生活质量。     

Tissue-engineered mesh for pelvic floor reconstruction fabricated from silk fibroin scaffold with adipose-derived mesenchymal stem cells

A tissue-engineered mesh fabricated with adipose-derived mesenchymal stem cells (AD-MSCs) cultured on a silk fibroin scaffold is evaluated for use in female pelvic reconstruction. Thirty-five female Sprague Dawley rats were divided into four groups. Group A (n?=?10) were implanted with polypropylene meshes, Group B (n?=?10) with silk fibroin scaffolds and Group C (n?=?10) with tissue-engineered meshes. Group D (n?=?5) acted as the tissue control. The tissue-engineered mesh was produced as follows. AD-MSCs were obtained from adipose tissue of rats designated to Group C. The cells were seeded onto a silk fibroin scaffold, cultured and then observed by scanning electron microscopy (SEM). Histological studies of these meshes were performed at 4 and 12 weeks after implantation and mechanical testing was carried out on all groups before implantation and at 12 weeks after implantation. AD-MSCs displayed fibroblast-like shapes and were able to differentiate into adipocytes or fibroblasts. SEM observation showed that AD-MSCs proliferated and secreted a matrix onto the silk fibroin scaffolds. After implantation of the scaffolds into rats, histological analysis revealed better organized newly formed tissue in Group C than in controls. Group C also had a similar failure force (2.67?±?0.15 vs 2.33?±?0.38 N) and a higher Young’s modulus (2.99?±?0.19 vs 1.68?±?0.20 MPa) than a normal vaginal wall, indicating the potential of this tissue-engineered approach. AD-MSCs were validated as seed cells for tissue engineering. The silk fibroin scaffold thus shows promise for application with AD-MSCs in the fabrication of tissue-engineered mesh with good biocompatibility and appropriate mechanical properties for pelvic floor reconstruction.     

A Retrospective Analysis of the Effectiveness of a Modified Abdominal High Uterosacral Colpopexy in the Treatment of Uterine Prolapse

To evaluate the clinical value of a novel method for high uterosacral colpopexy in the treatment of uterine prolapse. Thirty-one cases with severe pelvic organ prolapse diagnosed by pelvic organ prolapse quantification (POP-Q) system received a novel high sacral colpopexy method. Clinical parameters associated perioperative period and 12?months after surgery and complications were analyzed. A questionnaire survey on pelvic floor distress inventory and pelvic organ prolapse/urinary incontinence and sexual function was implemented. Between January 2007 and June 2008, 31 patients successfully received a Modified Abdominal High Uterosacral Colpopexy. The mean operation time was 50?±?15?min, and the average blood loss was 100?±?20?mls. 28 Patients returned for a 1-year follow-up, and the average follow-up period was 14?±?6?months. According to POP-Q system evaluation, the rate of operational success reached 100?%. There were no significant intraoperative and postoperative complications. A total of 31 responses on pelvic floor distress inventory short form questionnaire and 24 responses on pelvic organ prolapse/urinary incontinence sexual questionnaire showed that there was statistical significant difference before and after the procedure. This novel, high uterosacral colpopexy method is a safe and effective method for the treatment of uterine prolapse.     

经利用网片的前盆底重建术治疗重度盆腔器官脱垂的临床疗效

目的:探讨经利用网片的前盆底重建术治疗重度盆腔器官脱垂的临床效果。方法:选取2013年1月-2015年3月我院妇科收治的以前中盆腔联合缺陷为主的盆底障碍性疾病患者39例(POP-Q分度III-IV度)。实施经阴道Avaulta前盆腔重建术,24例切除子宫,9例保留子宫,其中6例因中盆腔重度脱垂联合行阴道残端骶棘韧带固定术,2例合并尿失禁同时行经尿道无张力悬吊术。术后随访12-25月,根据盆腔脏器脱垂评分(POP-Q)测量及PFIQ-7评分进行客观评价及主观感受评价进行中短期的临床效果分析。结果:39例患者手术过程顺利,术后无严重并发症,POP-Q评分均较术前显著降低,客观疗效理想。术后阴道前壁及子宫、阴道穹窿脱垂等症状显著改善;到目前为止无一例复发。结论:经阴道前盆腔重建术治疗前盆腔重度盆腔脱垂为主以及合并尿失禁等复杂情况的并发症少,治愈率高,复发率低,临床效果好。     

Expression of matrix metalloproteinase-1 in uterosacral ligaments tissue of women with genital prolapse

Collagen metabolism is altered in the pelvic organ tissues of women with genital prolapse. The aim of this study was to compare collagen metabolism by measuring matrix metalloproteinase-1 (MMP-1) expression in uterosacral ligament tissues of postmenopausal women with and without genital prolapse. Uterosacral ligament tissues were obtained at the time of abdominal or vaginal surgery from twenty-four patients with pelvic organ prolapse (POP) and 21 women who underwent gynecologic surgery for benign indications. The tissue samples were analyzed by immunohistochemistry. There were no differences in age, BMI and parity between two groups. The patients with genital prolapse demonstrated significantly higher occurences of MMP-1 expression compared to controls. These findings indicate that increased MMP-1 expression in uterosacral ligaments is associated with genital prolapse. Our data are consistent with the theory that increased collagen breakdown may play an important role in the onset and development of pelvic organ prolapse (POP).     

Quantification of pelvic organ prolapse in mice: vaginal protease activity precedes increased MOPQ scores in fibulin 5 knockout mice

Two mouse models of pelvic organ prolapse have been generated recently, both of which have null mutations in genes involved in elastic fiber synthesis and assembly (fibulin 5 and lysyl oxidase-like 1). Interestingly, although these mice exhibit elastinopathies early in life, pelvic organ prolapse does not develop until later in life. In this investigation we developed and validated a tool to quantify the severity of pelvic organ prolapse in mice, and we used this tool prospectively to study the role of fibulin 5, aging, and vaginal proteases in the development of pelvic organ prolapse. The results indicate that >90% of Fbln5(-/-) mice develop prolapse by 6 mo of age, even in the absence of vaginal delivery, and that increased vaginal protease activity precedes the development of prolapse.     

A Preclinical Evaluation of Alternative Synthetic Biomaterials for Fascial Defect Repair Using a Rat Abdominal Hernia Model

Introduction

Fascial defects are a common problem in the abdominal wall and in the vagina leading to hernia or pelvic organ prolapse that requires mesh enhancement to reduce operation failure. However, the long-term outcome of synthetic mesh surgery may be unsatisfactory due to post-surgical complications. We hypothesized that mesh fabricated from alternative synthetic polymers may evoke a different tissue response, and provide more appropriate mechanical properties for hernia repair. Our aim was to compare the in vivo biocompatibility of new synthetic meshes with a commercial mesh.

Methods

We have fabricated 3 new warp-knitted synthetic meshes from different polymers with different tensile properties polyetheretherketone (PEEK), polyamide (PA) and a composite, gelatin coated PA (PA+G). The rat abdominal hernia model was used to implant the meshes (25×35 mm, n = 24/ group). After 7, 30, 60, 90 days tissues were explanted for immunohistochemical assessment of foreign body reaction and tissue integration, using CD31, CD45, CD68, alpha-SMA antibodies. The images were analysed using an image analysis software program. Biomechanical properties were uniaxially evaluated using an Instron Tensile® Tester.

Results

This study showed that the new meshes induced complex differences in the type of foreign body reaction over the time course of implantation. The PA, and particularly the composite PA+G meshes, evoked a milder early inflammatory response, and macrophages were apparent throughout the time course. Our meshes led to better tissue integration and new collagen deposition, particularly with the PA+G meshes, as well as greater and sustained neovascularisation compared with the PP meshes.

Conclusion

PA, PA+G and PEEK appear to be well tolerated and are biocompatible, evoking an overlapping and different host tissue response with time that might convey mechanical variations in the healing tissue. These new meshes comprising different polymers may provide an alternative option for future treatment of fascial defects.     

Quantitative analysis of 17 amino acids in the connective tissue of patients with pelvic organ prolapse using capillary electrophoresis-tandem mass spectrometry

The simultaneous determination of 17 amino acids in connective tissue using capillary electrophoresis is described in this study. Separation was carried out on a fused silica capillary column (80 cm x 50 mm i.d.) with 1M formic acid as the running electrolyte. The detection was conducted on a mass spectrometer by selective reaction monitoring (SRM) mode via an electrospray ionization source. Tissue samples were prepared by reduction and acid hydrolysis to extract amino acids; over 84.3% recovery was seen for all compounds. The method allowed for sensitive, reproducible, and reliable quantification, and all 17 amino acids were separated using this method. Good linearity over the investigated concentration ranges was observed, with values of R higher than 0.993 for all the analytes. Precision and accuracy examined at three concentration levels ranged from 0.2% to 19.5% and 84.1% to 120.0%, respectively. Matrix effects were also tested and ranged from -9.1% to 15.4%. The validated method was applied to the quantitation of 17 amino acids in pelvic connective tissue of pelvic organ prolapsed patients. Methionine, glutamine, and histidine were significantly higher in the experimental patients compared to the controls. This suggests that changes in the amino acid concentrations within the connective tissue could be a factor in the genesis of pelvic organ prolapse. Therefore, this method is potentially applicable for amino acid analysis in tissue, providing a more complete understanding of pelvic organ prolapse.     

Prediction of nonlinear elastic behaviour of vaginal tissue: experimental results and model formulation

The mechanical properties of the vaginal tissue need to be characterised to perform accurate simulations of prolapse and other pelvic disorders that commonly affect women. This is also a fundamental step towards the improvement of therapeutic techniques such as surgery. Issues like the efficiency of using autologous tissue in pelvic reconstruction may be addressed. The goal of this study was to characterise the elastic behaviour of vaginal tissue. For this purpose, prolapsed vaginal tissue from eight different post-menopausal patients, excised during prolapse corrective surgery, was mechanically tested. The mechanical testing of vaginal tissue, consisting of uniaxial tension tests performed along the longitudinal axis of the vagina, revealed the nonlinear mechanical behaviour of the tissue. The material model parameters were fit to the experimental data using the Levenberg–Marquardt optimisation algorithm. All the curve fittings showed a good agreement between experimental and theoretical results, evidenced by R ² values close to 1 and by very low ? values.     

补中益气汤联合生物反馈电刺激在产后盆底功能障碍患者的应用研究

目的:研究探讨补中益气汤联合生物反馈电刺激对产后盆底功能障碍患者的临床治疗效果及对其盆底肌肉张力的影响。方法:选择我院就诊的90例产后盆底功能障碍气虚证患者(2017年11月～2018年10月),按照随机数字表法划分为30例/组的A组、B组、C组,A组实施常规盆底肌锻炼,B组采用盆底治疗仪实施生物反馈电刺激治疗,C组实施生物反馈电刺激联合中药补中益气汤治疗,比较三组的疗效、盆底肌力评分、阴道最大收缩压、盆腔器官脱垂、尿失禁、性生活质量评分。结果:(1)组间临床疗效、证候疗效比较,C组的临床总有效率、证候改善总有效率均高于A组、B组(P0.05),而A组与B组之间比较均无统计学差异(P0.05)。(2)治疗后,C组的盆底肌力评分、阴道最大收缩压、性生活质量评分均高于A组、B组(P0.05),A组与B组之间比较均无统计学差异(P0.05)。(3)C组的盆腔器官脱垂、尿失禁等发生率均低于A组、B组(P0.05),而A组与B组比较均无统计学差异(P0.05)。结论:生物反馈电刺激联合补中益气汤治疗可有效改善产后盆底功能障碍患者的盆底肌力和阴道压力,达到良好的临床疗效,有利于预防盆腔器官脱垂、尿失禁的发生,改善其性生活质量。     

基因多态性在盆底器官脱垂中的研究进展

盆底器官脱垂（Pelvic Organ Prolapse,POP）是遗传和环境因素共同作用引起的中老年妇女常见病,其发病率逐年上升。目前,环境因素已基本明确,而遗传因素尚未阐明。近年来,由于基因分型及遗传基因鉴定技术的快速发展,以及对盆底器官脱垂的群体调查及家系分析的增加,盆腔脏器脱垂的遗传研究有一定的进展,本文就其在基因多态性方面的发现做一综述。     

基因多态性在盆底器官脱垂中的研究进展

盆底器官脱垂(Pelvic Organ Prolapse,POP)是遗传和环境因素共同作用引起的中老年妇女常见病,其发病率逐年上升。目前,环境因素已基本明确,而遗传因素尚未阐明。近年来,由于基因分型及遗传基因鉴定技术的快速发展,以及对盆底器官脱垂的群体调查及家系分析的增加,盆腔脏器脱垂的遗传研究有一定的进展,本文就其在基因多态性方面的发现做一综述。     

Varying degrees of nonlinear mechanical behavior arising from geometric differences of urogynecological meshes

Synthetic polypropylene meshes were designed to restore pelvic organ support for women suffering from pelvic organ prolapse; however, the FDA released two notifications regarding potential complications associated with mesh implantation. Our aim was to characterize the structural properties of Restorelle and UltraPro subjected to uniaxial tension along perpendicular directions, and then model the tensile behavior of these meshes utilizing a co-rotational finite element model, with an imbedded linear or fiber-recruitment local stress–strain relationship. Both meshes exhibited a highly nonlinear stress–strain behavior; Restorelle had no significant differences between the two perpendicular directions, while UltraPro had a 93% difference in the low (initial) stiffness (p=0.009) between loading directions. Our model predicted that early alignment of the mesh segments in the loading direction and subsequent stretching could explain the observed nonlinear tensile behavior. However, a nonlinear stress–strain response in the stretching regime, that may be inherent to the mesh segment, was required to better capture experimental results. Utilizing a nonlinear fiber recruitment model with two parameters A and B, we observed improved agreement between the simulations and the experimental results. An inverse analysis found A=120 MPa and B=1.75 for Restorelle (RMSE=0.36). This approach yielded A=30 MPa and B=3.5 for UltraPro along one direction (RMSE=0.652), while the perpendicular orientation resulted in A=130 MPa and B=4.75 (RMSE=4.36). From the uniaxial protocol, Restorelle was found to have little variance in structural properties along these two perpendicular directions; however, UltraPro was found to behave anisotropically.     

Pelvic Organ Support in Animals with Partial Loss of Fibulin-5 in the Vaginal Wall

Compromise of elastic fiber integrity in connective tissues of the pelvic floor is most likely acquired through aging, childbirth-associated injury, and genetic susceptibility. Mouse models of pelvic organ prolapse demonstrate systemic deficiencies in proteins that affect elastogenesis. Prolapse, however, does not occur until several months after birth and is thereby acquired with age or after parturition. To determine the impact of compromised levels of fibulin-5 (Fbln5) during adulthood on pelvic organ support after parturition and elastase-induced injury, tissue-specific conditional knockout (cKO) mice were generated in which doxycycline (dox) treatment results in deletion of Fbln5 in cells that utilize the smooth muscle α actin promoter-driven reverse tetracycline transactivator and tetracycline responsive element-Cre recombinase (i.e., Fbln5^f/f/SMA⁺⁺-rtTA/Cre⁺, cKO). Fbln5 was decreased significantly in the vagina of cKO mice compared with dox-treated wild type or controls (Fbln5^f/f/SMA⁺⁺-rtTA/Cre^-/-). In controls, perineal body length (PBL) and bulge increased significantly after delivery but declined to baseline values within 6–8 weeks. Although overt prolapse did not occur in cKO animals, these transient increases in PBL postpartum were amplified and, unlike controls, parturition-induced increases in PBL (and bulge) did not recover to baseline but remained significantly increased for 12 wks. This lack of recovery from parturition was associated with increased MMP-9 and nondetectable levels of Fbln5 in the postpartum vagina. This predisposition to prolapse was accentuated by injection of elastase into the vaginal wall in which overt prolapse occurred in cKO animals, but rarely in controls. Taken together, our model system in which Fbln5 is conditionally knock-downed in stromal cells of the pelvic floor results in animals that undergo normal elastogenesis during development but lose Fbln5 as adults. The results indicate that vaginal fibulin-5 during development is crucial for baseline pelvic organ support and is also important for protection and recovery from parturition- and elastase-induced prolapse.     

补中益气汤联合低频脉冲电刺激促进产后盆底功能障碍的效果及血清松弛素、CTGF和MMP-1水平的影响

摘要 目的：探讨补中益气汤联合低频脉冲电刺激促进产后盆底功能障碍的效果及血清松弛素（RLX）、结缔组织生长因子（CTGF）和基质金属蛋白酶-1（MMP-1）水平的影响。方法：选取我院2022年4月到2023年4月收治的150例产后盆底功能障碍患者作为研究对象，分为观察组与对照组，各组均75例。对照组患者采取低频脉冲电刺激治疗，观察组患者采取补中益气汤联合低频脉冲电刺激治疗，对比两组患者的临床疗效，治疗前后盆底表面肌电变化情况，并分别在治疗前后应用盆腔脏器官脱垂-尿失禁性功能问卷（PISQ-12）、国际尿控协会盆腔脏器脱垂定量分析量表（POP-Q）、尿失禁问卷表简表（ICI-Q-SF）评估两组患者的性功能、盆腔脱垂程度及尿失禁情况，并对比治疗前后血清RLX、CTGF和MMP-1表达水平。结果：观察组总有效率93.33%明显高于对照组78.67%（P＜0.05）；两组患者治疗前耐力收缩（Ⅱ类肌）、持续收缩和快速收缩（Ⅰ类肌）、前静息电位、后静息电位肌电水平对比无差异（P＞0.05），治疗后观察组快速收缩（Ⅰ类肌）高于对照组（P＜0.05），静息电位与后静息电位低于对照组（P＜0.05）；两组患者治疗前PISQ-12、POP-Q和ICI-Q-SF评分对比无明显差异（P＞0.05），治疗后两组患者PISQ-12、ICI-Q-SF评分升高，观察组较对照组高，POP-Q评分均降低，观察组较对照组低（P＜0.05）；两组患者治疗前RLX、CTGF和MMP-1表达水平对比无差异（P＞0.05），治疗后两组患者RLX、CTGF和MMP-1表达水平均降低，且观察组低于对照组（P＜0.05）。结论：补中益气汤联合低频脉冲电刺激可提升产后盆底功能障碍的临床疗效，改善盆底肌表面肌电变化，改善患者性功能、盆腔脱垂程度及尿失禁情况，且能够降低血清松弛素、CTGF和MMP-1表达水平。     

Reduction of adhesions with composite AlloDerm/polypropylene mesh implants for abdominal wall reconstruction

Ventral hernia repair often includes the use of structural prosthetic materials, such as polypropylene mesh, that can induce dense abdominal adhesions to peritoneal structures. AlloDerm (LifeCell Corp., Branchburg, N.J.), a commercially available decellularized human dermal analogue with its native basement membrane components intact, is gradually revascularized and replaced with autologous tissue after implantation. The authors hypothesized that AlloDerm integrated with polypropylene mesh would reduce adhesions and provide a biodegradable scaffold to generate an autologous vascularized tissue layer separating the abdominal viscera from the mesh. Ventral hernia defects (3 x 1 cm) in 19 guinea pigs were repaired using an inlay technique with polypropylene mesh alone (n = 6) or with composite implants constructed by integrating polypropylene mesh and AlloDerm with its basement membrane surface oriented toward (polypropylene/AlloIn, n = 7) or away from (polypropylene/ AlloOut, n = 6) the peritoneal cavity. At 4 weeks, the authors determined the amount of mesh implant surface area covered by adhesions, the strength of the adhesions [graded from 0 (none) to 3], and the incidence of bowel adhesions. Histologic analyses were performed on full-thickness tissue sections from the repair sites. The mean surface areas affected by adhesions and mean adhesion strength were significantly lower in the polypropylene/AlloIn (area, 12.4 percent; mean grade, 1.0) and polypropylene/AlloOut (area, 9.5 percent; mean grade, 0.5) groups than in the polypropylene group (area, 79.5 percent; mean grade, 2.9); there were no such differences between the polypropylene/AlloIn and polypropylene/AlloOut groups. The bowel was adherent to 67 percent of polypropylene repairs and 0 percent of the composite mesh repairs. The AlloDerm was remodeled to form a vascularized tissue layer beneath the mesh in composite repairs, unlike the significantly thinner, dense scar layer that formed in the polypropylene repairs. Immunohistochemical labeling for factor VIII showed neovascularization throughout the AlloDerm.The AlloDerm thus functioned as a biodegradable tissue scaffold, guiding the formation of a thick, well-vascularized tissue layer separating the polypropylene mesh from intraperitoneal structures. This significantly reduced both the amount of surface area covered by adhesions and adhesion strength. Basement membrane orientation had no effect. Composite mesh implants composed of structural prosthetic materials integrated with AlloDerm may have useful clinical applications for abdominal wall reconstruction by reducing adhesions and providing a vascularized tissue layer to separate and protect the peritoneal structures from polypropylene mesh fibers.