Table 1.
Demonstrating a summary of all the animal studies published to PubMed assessing the safety and efficacy of pelvic mesh implants in the treatment of pelvic organ prolapse in the last 10 years
| Animal | Mesh | Site of insertion | Procedure | Follow-up (days) | Outcome | Comment | Country | Reference |
|---|---|---|---|---|---|---|---|---|
| Rat (Wistar) | Restorelle® | Anterior and posterior vaginal wall | PP mesh inserted via sacrocolpopexy in diabetes-induced and non-diabetic rats to assess inflammation. Following bilateral ovariectomy and supracervical hysterectomy | 3, 7 and 42 | Diabetes was associated with long-term inflammation, secondary to the dysregulated macrophage response | Diabetes is a known factor of inflammation, confirmed by results | USA | Liang et al. [1] |
| Pig (Yorkshire Crossed) | PP mesh | Vagina | Investigating the use of purified injectable exosome product to encourage tissue regeneration and treat ME. Meshes affixed with 2–0 PP sutures | 35 | Pigs treated with exosome injection and surgical correction saw highest incidence of ME resolution, followed by treatment with only exosome injection and no surgery | Note use of large pigs—70–80 kg. This was so that multiple meshes could be used per animal | USA | Kisby et al. [2] |
| Rabbit | PP mesh woven with thread of barium sulphate | Intraperitoneal flat inlay onto tissues | After 7 days, bloods were taken to assess acute toxicity. After 180 days, rabbits were euthanised to study histocompatibility and chronic toxicity | 7 and 180 | Adding radiopaque barium sulphate enables mesh visibility on X-ray imaging. Novel design is non-toxic and does not affect histocompatibility | Rabbits were suitable for testing toxicity and histocompatibility—no investigation for mesh efficacy | China | Li et al. [3] |
| Rat | PP mesh with pore sizes: | Abdominal wall | Plain textiles investigated using textile standards (NF-EN-13494–1). Mechanical characterisation performed using cyclic uniaxial tensile tests | 90 | Best outcomes with lighter mesh and low stiffness. Investigation into the effect of mechanical properties on native tissue | Results may not be suitable as the rat abdominal wall does not translate to the human pelvis | France | Morch et al. [4] |
| A—1.3 mm; B—2.2 mm; C—3.9 mm | ||||||||
| Rabbit (NZW) | Implant A: human cadaver skin tissue, 10 × 5 mm | Subcutaneous abdominal wall and post submucosa layer of vagina | Surgical procedure, clinical complications intra- and post-operatively including pain variable and analysis of explants studied | 180 | PP mesh had 33% ME rate. At 180 days, 40% of the biologic implants showed degradation. Few complications for abdominal implants | Difficulty obtaining adequate blood sample and vaginal field too small | Spain | Peró et al. [5] |
| Implant B: Gynaeband® PP mesh 10 × 5 mm and 5 × 5 mm | ||||||||
| Rabbit (NZW) | Mesh A: soft elastomer PDMS | Internal vagina | The mesh was implanted into the vagina following abdominal hysterectomy with preservation of the ovaries. Mesh A was heavier and less porous than PP mesh but with similar stiffness | 84 | Less negative reaction to mesh A with fewer complications and better structural morphology. Restorelle® was chosen as having least recorded functional and structural complications | Low stiffness important to prevent complications | USA | Knight et al. [6] |
| Mesh B: Restorelle® | ||||||||
| Pig (Yorkshire Crossed) | Restorelle® | Midventral and midrostral region of denuded vagina | ME model used following treatment using exosome injection. Restorelle® chosen for being PP mesh with greatest porosity and least stiffness | 84 | The studies confirmed the efficacy of using an injectable exosome regenerative platform to treat ME. Multi-dose treatment resulted in better tissue regeneration | This team has performed two similar studies of this kind; this one tests dosages required | USA | Kisby et al. [7] |
| Rat (SD) | Mesh A: novel biomaterial, PCU, 3D printed crosshatch design 1-mm pores | Vagina | Supracervical hysterectomy and ovariectomy first performed, then mesh implanted | 90 | PCU has less stiffness and greater tensile strength than PP and is therefore less likely to result in mesh erosion and pain complications. Similar inflammatory response to both PCU and PP mesh | Small mesh constructs used as rats too small. Not placed under tension, which may affect results | USA | Bickhaus et al. [8] |
| Mesh B: lightweight, knitted PP mesh 1.5-mm pores | ||||||||
| Rat (SD) | Lightweight PP meshes with 1.5-mm pore size | Vagina and proximal vs distal lumbar vertebrae | Comparison between sham operation only (control), mesh sutured only on the vagina (vaginal mesh), sacrocolpopexy without tension, and sacrocolpopexy with tension | 90 | Attachment of prolapse mesh resulted in an increased histological inflammatory response independent of tension | Ovariectomy to cancel hormonal effects on outcomes | USA | Bickhaus et al. [9] |
| Rat (Wistar) | Mesh A: biodegradable polymer 65% polycaprolactone and 35% polytrimethylene carbonate | Inter-fascial space between dorsal muscles (back) | Each rat had two meshes placed at the back, experimental and PP mesh, each 1 × 1 cm | 90 and 180 | Mesh A degraded by 9% over 6 months, noted to be too fast to allow tissue regeneration. More fibrosis noted with biopolymer matrix, which is ideal for managing POP | Biodegradable polymer not suitable for long-term prolapse support | Russia | Eisenakh et al. [10] |
| Mesh B: PP mesh | ||||||||
| Rat (SD) | Gynemesh® | Vagina | Ovariectomy performed 1 week prior to mesh implantation. PP mesh seeded with human umbilical cord-derived stem cells | 7, 28 and 84 | At 12 weeks, better outcomes with stem cells seeded PP mesh with host response and tissue regeneration | Testing stem cells coating on larger animals would provide more accurate results | China | Deng et al. [11] |
| Rat (SD) | Mesh A: novel polycarbonate material based on fourfold hydrogen bonding ureidopyrimidinone | Abdominal wall | Abdominal wall was reconstructed with mesh in the rat hernia model | 2, 7, 14, 28 and 90 | Results showed that mesh A resulted in better tissue integration and ingrowth, with reduced scar formation | The results are unlikely to be accurate as the rat abdominal wall hernia model was used, which does not translate to vaginal prolapse | European | Mori da Cunha et al. [12] |
| Mesh B: pristine-based mesh | ||||||||
| Sheep | Mesh A: polyamide-based mesh; B: same as A but dip-coated in gelatin and stabilised with 0.5% glutaraldehyde; C: same as B, but seeded with autologous ovine eMSCs | Posterior vaginal wall, rectovaginal space | Subtotal hysterectomy via ventral midline laparotomy 4 weeks prior to mesh implantation. Mesh implantation via transvaginal surgery of the posterior vaginal wall | 30 | Mesh A had the best outcomes, then mesh C. eMSCs had a role in replenishing and retaining muscle cells surrounding the uterus. eMSCs in mesh C resulted in better histological outcomes and tissue integration than in mesh B | This study tested implants for biocompatibility and toxicity, as well as treatment efficacy by measuring improvement in POP using POP-Q measurements | Australia | Emmerson et al. [13] |
| Rat (Wistar) | Type 1 PP monofilament macroporous mesh | Abdominal fascia and muscles in the four corners of the abdominal wall | Vertical abdominal cutaneous incision and abdominal fascia dissection. Measuring ideal endpoint for animal study follow-up | 30, 60, 90, 120 and 150 | Mechanical properties of implants evolve over time as they integrate with native tissue. In this situation—abdominal fascia of rats, mechanical properties stabilised after 2 months | Extremely useful research for the design of animal studies, 2 months proposed as a suitable minimal endpoint | France | Doucède et al. [14] |
| Sheep | Mesh A: titanised PP lightweight mesh—TiLOOP | Rectovaginal septum | Posterior vaginal wall dissected from the perineal body to the vaginal apex along the midline. Mesh implanted between the rectum and the vaginal epithelium | 7 and 84 | Mesh A showed less inflammation at 1 week. At 12 weeks, there was no significant difference between the biomechanical properties of mesh A and mesh B | The research team was able to follow this study with a clinical trial | China | Ai et al. [15] |
| Mesh B: Gynemesh® | ||||||||
| Rabbit (NZW) | Restorelle® | Anterior and posterior vagina | Mesh implanted into the anterior and posterior vagina via lumbar colpopexy after hysterectomy, with preservation of the ovaries | 84 | Rabbit is similar enough to cautiously use for histological studies for POP, noting differences | Increased availability of rabbits and cheaper, good alternative | USA | Knight et al. [16] |
| Mouse | Mesh A: biodegradable PCL, aloe vera-sodium alginate hydrogel and eMSCs | Abdominal wall | Following sharp dissection of the abdominal wall, blunt dissection was used to create a subcutaneous pocket to insert the mesh | 7 | Good biocompatibility and tissue integration. The eMSCs were retained until endpoint. Mesh A, which included eMSCs, had most positive outcomes | Short-term test on smaller animal unlikely to translate to human studies | Australia | Paul et al. [17] |
| Mesh B: PCL construct | ||||||||
| Mesh C: Mesh A without eMSCs | ||||||||
| NHP | Mesh A: Gynemesh® + two-ply MatriStem | Anterior/posterior vagina wall and longitudinal ligament of the sacrum | MatriStem is an extracellular matrix bioscaffold derived from urinary bladder matrix. Mesh is implanted via sacrocolpopexy following a hysterectomy | 90 | Mesh B had poor outcomes of vaginal atrophy and reduced vaginal smooth muscle contractility; mesh A attenuated this impact. Mesh C had increased vaginal smooth muscle but no other significant changes | Use of gold-standard non-human primate supports the accuracy of the results | USA | Shaffer et al. [18] |
| Mesh B: Gynemesh® | ||||||||
| Mesh C: six-ply MatriStem scaffold | ||||||||
| Sheep | Mesh A: novel mesh of bacterial cellulose | Midline between rectum and vaginal epithelium |
Mesh was smoothed prior to implantation to prevent any folds Bacterial cellulose mesh is developed via fermentation of Acetobacter xylinum with natural ingredients including coconut water and sugar cane molasses |
7 and 84 | Mesh A induced a greater inflammatory response than the comparator at both endpoints. Biomechanical properties met minimal requirements to treatment of POP, but no improvement compared with mesh B | The outcomes were not promising for the use of mesh A to treat POP; other alternatives currently at the same stage have improved outcomes | China | Ai et al. [19] |
| Mesh B: Gynemesh® | ||||||||
| Rat (Wistar) | Mesh A and B: PCL—2 doses of fibroblast growth factor | Abdominal wall | The PCL meshes were fabricated via electrospinning then coated with a hydrogel containing either fibroblast growth factor or connective tissue growth factor. Mesh A and B: hollow fibre. Mesh C, D, E and F: solid fibre | 56 and 168 | High-dose fibroblast growth factor did not improve collage formation. Hollow fibre mesh underwent total degradation at 24 weeks compared with solid fibre. Mesh E including stem cells was the only mesh not causing complications and had best biomechanical outcomes | Number of mesh studies in rat models but ideally a larger animal would be used to test treatment with more than one mesh per animal | Denmark | Hansen et al. [20] |
| Mesh C and D: PCL—with and without fibroblast growth factor | ||||||||
| Mesh E and F: PCL and connective tissue growth factor—with and without rat mesenchymal stem cells | ||||||||
| Mouse | Meshes A: poly(L-actic acid)-co-PCL; B: mesh A + gelatin; C: mesh A + eMSCs; D: mesh A + gelatin + eMSCs | Abdominal wall | Mesh implanted via longitudinal skin incision of lower abdomen. Two mesh inserted per animal | 7 and 42 | All mesh biomechanical properties were satisfactory. Mesh D with gelatin and eMSCs had the best outcomes in terms of anti-inflammatory response and tissue integration. Combination with gelatin increased retention of eMSCs | Biomechanical properties would not be translatable as mice are much smaller than humans and have different mechanical properties | Australia | Mukherjee et al. [21] |
| Rat and rabbit | Mesh A: PCL modified with ureidopyrimidinone |
Rat: left hemi-abdominal wall Rabbit: right lower and left upper quadrant |
Rat: herniation made in abdominal wall Rabbit: each rabbit is implanted with two meshes in abdominal wall |
Rat: 7, 42 and 54 Rabbit: 30 and 90 |
In both animals, compliance of mesh A was similar to that of native tissue. In rats, mesh B was stiffer. Foreign body giant cells were present increasingly in tissues where degradation had taken place | Would be better to separate papers for each animal to avoid confusion regarding results | European | Hympanova et al. [22] |
| Mesh B: Restorelle® | ||||||||
| Sheep | Mesh A: Restorelle® | Rectovaginal septum, 3 cm from the hymenal ring | Posterior vaginal wall surgery took place with mesh inserted at the rectovaginal septum | 60 and 180 | Mesh B had partially degraded in 90% of sheep at 180 days but meshes A and C remained fully intact. Biomechanical properties were similar amongst all groups | Biodegradable mesh had degraded by the endpoint, as would be expected; however, biomechanical properties similar amongst groups | European | Hympánová et al. [23] |
| Mesh B: biodegradable ureidopyrimidinone-polycarbonate | ||||||||
| Mesh C: non-degradable polyurethane | ||||||||
| Rat | Mesh A: standard weight PP mesh 72 g/m2 | Abdominal wall | Each rat had two meshes inserted on either side of the midline incision of the abdominal wall | 4 and 30 | There was no significant difference in outcomes for mesh A and mesh B | Similar results may be due to a lack of longer-term follow-up | Brazil | Bronzatto and Riccetto [24] |
| Mesh B: lightweight PP mesh 16 g/m2 | ||||||||
| Rat | Mesh A: polylactic acid and PCL microfibres electrospun onto PP mesh | Onlay position in abdomen | Meshes were processed as described prior to implantation into the rat model, in abdominal subcutaneous tissue | 14 and 28 | Mesh A had better outcomes in terms of tissue regeneration and adhesion resulting in integration. The thickness of mesh A increased most at both endpoints, likely because of tissue growth on the surface | Investigation of the fabrication method of two meshes. Analysis lacks robustness, with conclusions made on assumptions | China | Lu et al. [25] |
| Mesh B: PP mesh immersed in polylactic acid and PCL solution | ||||||||
| Rat (SD) | Mesh A: Gynemesh® | Posterior vaginal wall | Initially, subjects underwent ovariectomy 1 week prior to mesh implantation. Note that meshes were prepared with either human umbilical mesenchymal stem cells or smooth muscle cell-differentiated stem cells | 7, 28, 56 and 84 | Meshes B, C and D had better outcomes than mesh A. There were thicker layers of tissue growth on all meshes with stem cells. Mesh D had the most promising results | Consideration of the accuracy of results with implantation of human stem cells into the rat model | China | Ding et al. [26] |
| Mesh B: mesh A and human umbilical cord stem cells | ||||||||
| Mesh C: mesh A and smooth muscle cell-differentiated stem cells | ||||||||
| Mesh D: mesh C and human umbilical cord stem cells | ||||||||
| Sheep | Mesh A: PVDF mesh with arms | Beyond rectovaginal septum | MR imaging was taken of mesh in vivo to investigate mesh changes in shape and geometry following implantation | 2, 14 and 60 | Mesh A had the least surface area decrease compared with mesh B, occurring immediately post-operatively. Mesh size was mostly stable afterwards | Novel methods assess the outcomes of significant mesh shrinkage | Belgium | Iva et al. [27] |
| Mesh B: flat PVDF mesh | ||||||||
| Rat (SD) | Mesh A: PCL modified with ureidopyrimidinone | Abdominal wall defect | Full-thickness abdominal defect created then repaired and reinforced with mesh | 7 and 42 | Mesh A does not compromise physiological compliance and was not fully degraded at 42 days. Mesh B’s biomechanical properties remain far from physiological compliance | Biomechanical properties were recorded; however, the rat model was not translatable to the human vagina for prolapse | European | Hympanova et al. [28] |
| Mesh B: Restorelle® | ||||||||
| Rabbit (NZW) | Mesh A: knitted design pure polylactic acid | Four quadrants of abdominal wall—onlay position | Each subject had four meshes implanted, two of each type on either side of the midline incision | 30, 90 and 180 | Biocompatibility was similar in both meshes. Surrounding tissue to mesh A recovered better than that to mesh B. There was increased tissue regeneration and reduced shrinkage with mesh A | It was recognised that repeating the experiment in a sheep model would provide more accurate results | Australia and China | Lu et al. [29] |
| Mesh B: Surgimesh® Prolapse, lightweight and large pore PP mesh | ||||||||
| NHP | Six-ply MatriStem scaffold | Vagina | All animals underwent hysterectomy and complete transection of uterosacral ligaments and paravaginal attachments to the pelvic sidewall prior to the procedure. Mesh implanted either via the transvaginal or the transabdominal route | 90 | Good overall biocompatibility was recorded. Transvaginal insertion resulted in poorer outcomes, adjacent to the site of incision | No active control group. Results from a previous study were used for sham comparison. Note the gold standard animal model | USA | Liang et al. [30] |
| Rat (Wistar) | Mesh A: Parietex Composite® Covidien multifilament polyester mesh | Between the posterior cervix and the anterior longitudinal ligament of the lumbar vertebrae | Mesh A was fabricated using polyethylene terephthalate coated with porcine collagen-polyethylene glycol and glycerol | 14 | Mesh A had better adhesion outcomes; however, it also caused a more pronounced host inflammatory response and foreign body reaction | Note that the strong host inflammatory response in mesh A was anticipated | Turkey | Gokmen-Karasu et al. [31] |
| Mesh B: Surgipro® macroporous multifilament PP mesh | ||||||||
| Rat (Wistar) | PCL and polyethylene oxide | Abdominal wall | Mesh combined with basic fibroblast growth factor versus mesh implantation. Mesh implanted at the site of full-thickness fascia-muscle defect | 28, 56 and 168 | Growth factors prevented degradation of mesh for 28 days. Positive outcomes recorded but degradation occurred too fast to support tissue regeneration | Longer follow-up would have allowed assessment of the full degradation of the implant | Denmark | Glindtvad et al. [32] |
| Rats (Wistar) | Mesh A: heavy weight PP mesh 62 g/m2 | Abdominal wall | Mesh implanted between the hypodermis and abdominal muscular fascia. Mesh A as per the standard procedure. Mesh B was implanted in both the transverse plane and the longitudinal plane | 7, 30 and 60 | Implanting mesh B in the transverse plane exhibited similar outcomes to mesh A. Less stiffness and maximum load were seen with longitudinal plane implantation | This research confirms that physical and textile implant properties greatly effect clinical outcomes | Brazil | Bigozzi et al. [33] |
| Mesh B: lightweight PP mesh 16 g/m2 | ||||||||
| Rabbit (NZW) | Mesh A: 1 × 1 cm PP mesh | Abdominal wall | Mesh implanted between the hypodermis and abdominal muscular fascia. Collagen I, II and inflammatory infiltrate levels were analysed at implant site | 7, 30 and 90 | Coating PP mesh with platelet-rich plasma enhanced tissue regeneration with higher total collagen concentration | Promising results; however, it is unclear if these histology outcomes will result in better clinical outcomes | Brazil | Avila et al. [34] |
| Mesh B: mesh A coated with platelet-rich plasma extracted from blood via centrifuge | ||||||||
| Rabbit | Mesh A: PP mesh | Abdominal wall | Meshes C and D were compared as alternative materials to commercially available Meshes A and B. Implants were placed in full-thickness abdominal wall defects | 30 and 90 | Meshes C and D had better outcomes, with decreased inflammatory response | Promising results regarding alternative materials; however, these would need replication in larger animal models | Belgium and UK | Sabiniano et al. [35] |
| Mesh B: PVDF mesh | ||||||||
| Mesh C: polyurethane mesh | ||||||||
| Mesh D: poly-L-lactic acid | ||||||||
| Sheep | EndoFast Reliant™ System | Thigh fascia | EndoFast Reliant™ System was used to insert mesh into sheep thigh fascia. Pullout force was measured at each endpoint | 0, 3, 7, 15, 30 and 45 | Test to investigate the strength of attachment; results showed that the experimental system provided much stronger mesh attachment than trocar-based methods | Sheep thigh was used as the site of implantation owing to histological similarity, rather than vagina tissue | Israel | Alcalay et al. [36] |
Only papers written in English language were included in the table
eMSCs endometrial mesenchymal stem cells, ME mesh exposure, NHP non-human primate, NZW New Zealand White, PCL poly ε-caprolactone, PCU polycarbonate urethane, PDMS polydimethylsiloxane, POP pelvic organ prolapse, PP polypropylene, PVDF polyvinylidene fluoride, SD Sprague–Dawley