In Vivo Evaluation of a Biodegradable Intraanastomotic Membrane in a Porcine Model

In Vivo Evaluation of a Biodegradable Intraanastomotic Membrane in a Porcine Model | medRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-P4HH5NV'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search In Vivo Evaluation of a Biodegradable Intraanastomotic Membrane in a Porcine Model View ORCID Profile Daniel C. Freund , View ORCID Profile Dennis Wahl , View ORCID Profile Eberhard Grambow , View ORCID Profile Finn Jaekel , View ORCID Profile Julia Henne , View ORCID Profile Richard Kantelberg , View ORCID Profile Hans Kleemann , Friedrich Prall , View ORCID Profile Amelie R. Zitzmann , View ORCID Profile Brigitte Vollmar , View ORCID Profile Jochen Hampe , View ORCID Profile Karl Leo , View ORCID Profile Sebastian Hinz , View ORCID Profile Clemens Schafmayer doi: https://doi.org/10.1101/2025.10.10.25337726 Daniel C. Freund 1 Department of General, Visceral, Thoracic, Vascular and Transplantation Surgery, Rostock University Medical Center , Rostock, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Daniel C. Freund For correspondence: daniel.freund{at}uni-rostock.de Dennis Wahl 1 Department of General, Visceral, Thoracic, Vascular and Transplantation Surgery, Rostock University Medical Center , Rostock, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Dennis Wahl Eberhard Grambow 1 Department of General, Visceral, Thoracic, Vascular and Transplantation Surgery, Rostock University Medical Center , Rostock, Germany 5 Department of Cardiac, Thoracic and Vascular Surgery, University Medical Center Göttingen Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Eberhard Grambow Finn Jaekel 7 Integrated Center for Applied Physics and Photonic Materials (IAPP), Technical University of Dresden , Dresden, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Finn Jaekel Julia Henne 1 Department of General, Visceral, Thoracic, Vascular and Transplantation Surgery, Rostock University Medical Center , Rostock, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Julia Henne Richard Kantelberg 7 Integrated Center for Applied Physics and Photonic Materials (IAPP), Technical University of Dresden , Dresden, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Richard Kantelberg Hans Kleemann 7 Integrated Center for Applied Physics and Photonic Materials (IAPP), Technical University of Dresden , Dresden, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Hans Kleemann Friedrich Prall 2 Institute of Pathology, University Medical Center Rostock , Rostock, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site Amelie R. Zitzmann 3 Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Medical Centre of Rostock , Rostock, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Amelie R. Zitzmann Brigitte Vollmar 4 Rudolf-Zenker-Institute for Experimental Surgery, University Medical Center Rostock , 18057 Rostock, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Brigitte Vollmar Jochen Hampe 6 Department of Medicine I, University Medical Center Dresden, Technische Universität Dresden , Dresden, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Jochen Hampe Karl Leo 7 Integrated Center for Applied Physics and Photonic Materials (IAPP), Technical University of Dresden , Dresden, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Karl Leo Sebastian Hinz 1 Department of General, Visceral, Thoracic, Vascular and Transplantation Surgery, Rostock University Medical Center , Rostock, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Sebastian Hinz Clemens Schafmayer 1 Department of General, Visceral, Thoracic, Vascular and Transplantation Surgery, Rostock University Medical Center , Rostock, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Clemens Schafmayer Abstract Full Text Info/History Metrics Supplementary material Data/Code Preview PDF ABSTRACT Background Anastomotic leakage (AL) represents one of the most serious complications in gastrointestinal surgery, with reported incidence rates of up to 26 %. Despite advancements in surgical techniques, early detection of AL remains challenging, and no reliable real-time monitoring system is currently available. In this study, we investigated a resorbable polydioxanone (PDO) membrane as a potential substrate for future sensor integration, aiming to facilitate real-time monitoring of anastomotic healing. Methods In eight German Landrace pigs, 34 ileal side-to-end stapler anastomoses were examined: GM1 (n = 7), GM2 (n = 10), and controls (n = 17). Membrane stability was monitored after implantation, while adhesion formation, burst pressure, and histology were assessed on postoperative day 7. Results Both membrane geometries showed robust stability, with good anchorage of the large spokes within the anastomosis. Geometry 1 (GM1) exhibited higher burst pressure than Geometry 2 (GM2) (193 ± 43.6 vs 155 ± 65.5 mmHg, p = 0.02). Compared with controls (167 ± 42.3 mmHg), neither GM1 (p = 0.053) nor GM2 (p = 0.379) differed significantly. Adhesions occurred in all groups, without significant differences. Histological evaluation showed typical granulation tissue and fibrosis, with granulocytic inflammation more common in GM1 without affecting anastomotic stability. Conclusion This proof-of-concept study demonstrates that the PDO membrane can be safely incorporated into stapled anastomoses without compromising anastomotic healing. The membrane provides a stable, biocompatible platform suitable for future sensor integration, supporting the development of a diagnostic intraanastomotic device. 1 INTRODUCTION Anastomotic leakage (AL) remains one of the most serious postoperative complications in visceral surgery, with incidence rates of up to 26 %, leading to significantly increased patient morbidity and mortality 1 – 3 . In addition, AL is associated with prolonged hospitalization and substantial economic burden 4 . Although early detection of anastomotic complications is critical, it remains a major clinical challenge. On average, AL is diagnosed five to eight days postoperatively 5 – 7 , typically based on clinical signs and nonspecific laboratory parameters, such as elevated inflammatory markers. Early diagnosis has been shown to markedly improve patient outcomes 8 , 9 . Currently, no reliable methods exist for early detection of AL 10 , 11 . The aim of this study was to develop a resorbable membrane as a potential platform for future integration of sensors, enabling real-time intraanastomotic monitoring of impaired healing, facilitating timely interventions, and potentially preventing progression to full AL. Polydioxanone (PDO) was selected for membrane fabrication due to its well-established biocompatibility and controllable hydrolytic degradation 12 . We hypothesized that incorporation of a PDO membrane into side-to-end stapled anastomoses would not compromise healing and could provide a stable, biocompatible scaffold for future sensor integration. 2 MATERIALS AND METHODS 2.1 Membrane Design All membranes were fabricated from 150 µm thick PDO sheets (Ethicon, Inc., a Johnson & Johnson company, Somerville, NJ, USA). Following preliminary in vitro testing of multiple design concepts ( Fig. 1A , top), two designs were selected for their favourable tissue disruption ratio, structural stability, and compatibility with the stapling device. These geometries were subsequently evaluated in the present in vivo study ( Fig. 1A , bottom). Download figure Open in new tab Figure 1: Schematic and macroscopic images of the PDO membrane with different geometries and spokes for fixation in the small bowel anastomosis. The lower photo displays GM1 (left) and GM2 (right). Each design includes four large and eight narrow spokes. (A) . PDO membrane before (B) and after implanting in a small bowel (C) stapler anastomosis. The anvil of the stapler with bowel margins and inner ring of the PDO membrane (D) . 2.2 Animal Model The experimental cohort consisted of eight male German Landrace pigs, aged 12 to 16 weeks and weighing 31.6–41.0 kg (mean ± SD: 36.0 ± 3.2 kg). Another animal died prematurely due to surgical error and was excluded from the study. Post-mortem examination identified small bowel torsion proximal to the anastomotic sites. The anastomoses showed no abnormalities. Animals were housed under standardized conditions at the Central Animal Care Facility of Rostock University Medical Center and acclimatized for seven days prior to the procedure. Water was provided ad libitum until one day before the procedure. Premedication and anesthesia were administered according to the standard protocols of the Institute for Experimental Surgery at Rostock University Medical Center. All in vivo experiments were conducted in compliance with the German legislation on protection of animals (7221.3-1-050/19) and the NIH Guide for the Care and Use of Laboratory Animals (Institute of Laboratory Animal Resources, National Research Council) 14 . 2.3 Sedation and Anesthesia Premedication was administered intramuscularly with 8 mg/kg azaperone (Stresnil™, Elanco, Cuxhaven, Germany), 20 mg/kg ketamine (10 % Ketamin, Medistar Arzneimittelbetrieb GmbH, Ascheberg, Germany) and 0.2 mg/kg midazolam (Dormicum, Hoffmann La Roche AG, Grenzach-Wyhlen, Germany). Animals were equipped with a pulse oximeter (Nellcor ® PM10N, Medtronic, Watford, UK) placed on the tail and two peripheral venous cannulas (20G, B. Braun Melsungen AG, Melsungen, Germany) in the earlobe veins. Anesthesia was induced with 200 µg fentanyl (Fentadon ® 50µg/ml, Eurovet Animal Health BV, Bladel, Netherlands), 100 mg propofol (Propofol 2%, MCT Fresenius, Bad Homburg, Germany) and 4 mg pancuronium (Pancuronium Inresa 4mg/2ml, Inresa Arzneimittel GmbH, Freiburg, Germany). Maintenance anesthesia was provided via total intravenous anesthesia (TIVA) with fentanyl (5-10 µg kg -1 h -1 ), propofol (4–8 mg kg -1 h -1 ), and midazolam (0.1 mg kg -1 h -1 ) 13 . Endotracheal intubation was performed using a 7 mm inner-diameter tube, followed by volume-controlled ventilation with a Dräger Primus ® ventilator, while continuously monitoring oxygen saturation, heart rate, respiratory minute volume, and end-expiratory CO 2 . Following induction, animals were placed in the supine position on the operating table and secured at all extremities. 2.4 Surgical Model After sterile preparation using Braunol ® (B. Braun Melsungen AG, Melsungen, Germany), a midline laparotomy was performed with a careful right-sided incision around the urethra. Anastomoses were created at intervals of approximately 50 cm oral to the ileocecal valve. Side-to-end stapler anastomoses were constructed in the small intestine, allowing multiple anastomoses per animal to reduce the number of animals required for the study. After an initial mesenteric incision between the marginal arteries, the bowel was transected using monopolar cautery (ICC 300, Erbe Elektromedizin, Tübingen, Germany). The stapler anvil was inserted into the oral end of the bowel and secured with a preplaced purse-string suture (Vicryl 3.0, Ethicon ® , Inc., a Johnson & Johnson company, Somerville, NJ, USA). The stapler (21 mm Ethicon™ Circular Stapler, Ethicon ® , Inc., a Johnson & Johnson company, Somerville, NJ, USA) was then introduced into the aboral end, and the intestine was pierced with the trocar opposite the mesenteric side. The PDO membrane was positioned on the stapler trocar, the stapler components were connected ( Fig. 1B ), and the intestinal ends were approximated by gradually closing the stapler. The stapler was then fired, excising the inner membrane section to ensure anastomotic patency and prevent luminal obstruction ( Fig. 1D ). Following stapler removal, the blind end was resected, leaving approximately 1 cm of bowel to prevent ischemia around the anastomosis, and closed with a running suture (PDS 4-0, Ethicon ® , Inc., a Johnson & Johnson company, Somerville, NJ, USA ( Fig. 1C ). In total, 34 ileal side-to-end anastomoses were examined, subdivided into three groups: GM1 (n = 7), GM2 (n = 10), and control (n = 17). Membranes were inspected for spoke displacement, and the intestines were repositioned. The abdominal wall was closed with a fascial suture (PDS sling 1.0, Ethicon ® , Inc., a Johnson & Johnson company, Somerville, NJ, USA) and a skin staple closure (Disposable Skin Stapler F35w, ADVAN, China), followed by application of silver-aluminum spray to the wound. Depending on intraabdominal conditions, three to five anastomoses were performed per animal. Postoperatively, animals received water ad libitum and a standardized diet (2 × 300 g MPig-H, ssniff ® , Soest, Germany). Oral analgesia was provided daily with 2 g metamizole (Novaminsulfon 500 mg/ml, Winthrop Arzneimittel GmbH, Frankfurt, Germany). Wounds were treated daily with iodine solution. Animal well-being was monitored using a standardized distress score (see Supplementary Material). 2.5 Relaparotomy, Macroscopic Evaluation and Burst Pressure Measurement Relaparotomy was scheduled on postoperative day seven. One animal underwent relaparotomy on postoperative day five due to an elevated distress score (apathy and immobility), in accordance with the predefined study criteria. No pathological findings were detected intraoperatively, and the anastomoses remained included in the analysis. One animal underwent relaparotomy on the tenth day. The abdominal cavity was inspected for signs of complications such as peritonitis, inflammation, or bowel obstruction. The anastomoses were then identified and evaluated for macroscopic integrity and adhesion formation. Adhesions were graded according to the van der Ham score 15 as follows: 0 = no adhesions; 1+ = minimal adhesions, primarily between the anastomosis and the omentum; 2+ = moderate adhesions, involving the omentum, anastomotic site, and adjacent small bowel loops; and 3+ = severe and extensive adhesions, including abscess formation ( Fig. 2A, B ). For assessment of anastomotic burst pressure, the bowel was incised 5 cm proximal and distal to the anastomosis. A catheter was inserted for isotonic saline infusion and another for pressure measurement. Both ends were securely closed, and the catheters were sealed with cable ties ( Fig. 2C ) 16 . The bowel segment was then continuously filled until rupture occurred, and the peak intraluminal pressure was recorded 17 . The rupture site was documented as occurring either at the anastomosis or at a distant bowel segment. Finally, while under general anesthesia, animals were euthanized with 45 mg·kg −1 pentobarbital (Release ® 300mg/ml, Wirtschaftsgenossenschaft Deutscher Tierärzte eG., Garbsen, Germany). Download figure Open in new tab Figure 2: Postoperative macroscopic analysis of small bowel anastomoses on day seven. The scissors point to an adhesion (2+) (A) . Adhesion and fibrin deposition (1+) (B) . For burst pressure analysis, catheters for saline infusion (left tube) and pressure analysis (right tube) were inserted near the anastomosis and secured using cable ties (C) . Resected anastomosis for macroscopical study after midline incision (D) . 2.6 Histological Analysis Intestinal segments containing the anastomoses were excised, opened along the antimesenteric border ( Fig. 2D ), and fixed in a stretched position in 10 % buffered formalin for 24 hours 18 . After careful removal of the metallic stapler clips, two longitudinal tissue sections, one from the mesenteric and one from the antimesenteric side, were obtained from each specimen (approximately 25 mm in length and 4 mm in thickness), with the anastomotic site positioned centrally 19 . The samples were embedded in paraffin and sectioned into 4 µm slices using a microtome (Leica RM 2145). All sections were stained with hematoxylin and eosin (H&E) and examined by a surgical pathologist blinded to the group (with or without membrane). 2.7 Statistical Analysis All statistical analyses were performed using IBM SPSS Statistics for Windows, Version 29.0.2.0 (IBM Corp., Armonk, NY, USA). The Mann–Whitney U test was applied to assess differences in burst pressure between groups. The Fisher–Freeman–Halton test was used to evaluate the significance of all other data, and the Jonckheere–Terpstra test was applied to analyze the van der Ham adhesion scores. Continuous variables are presented as medians. A p-value < 0.05 was considered statistically significant. 3 RESULTS 3.1 Membrane Design and Stability After initial design optimization, two membrane prototypes were evaluated in vivo . Both designs comprised an outer ring (28.88 mm outer diameter, 21.38 mm inner diameter) connected to an inner ring (10 mm outer diameter) by eight narrow and four wide spokes ( Fig. 1A ). GM1 featured 1.5 mm-wide spokes, while GM2 incorporated 2.0 mm-wide spokes; both designs included 0.6 mm narrow spokes. A central circular cutout (6.4 mm) accommodated the trocar of a 21 mm circular stapler, with additional peripheral cuts aligned to the trocar’s widest points to prevent rotation or dislocation during implantation. The spoke configuration was designed to maximize surface area for future sensor integration while maintaining stable anchoring and minimizing the amount of material embedded within the intestinal wall to reduce interference with anastomotic healing. After stapled implantation, membranes were examined for dislocation or structural damage ( Fig. 3A ). Outer ring damage was observed in one GM1 anastomosis. Dislocation of large spokes was infrequent (GM1: 14.3 %; GM2: 20.0 %; p = 0.640; Fig. 3A ). Small spoke dislocation occurred in both geometries: in GM1, 43.9 % of anastomoses showed all small spokes intact, none exhibited single spoke dislocation, and 57.1 % showed dislocation of two spokes; in GM2, 40.0 % had all spokes intact, 30.0 % exhibited dislocation of one spoke, and 30.0 % showed dislocation of two spokes. There was no statistically significant difference in the rate or extent of small spoke dislocation between groups (p = 0.358). Download figure Open in new tab Figure 3: Quantitative analysis of PDO membrane stability immediately after implantation in a small bowel stapler anastomosis. Stability was assessed by dislocation large spokes of the membrane. No significant differences between the groups ( p = 0.640; Fisher–Freeman–Halton test) (A) . Analysis of anastomotic stability. Quantitative assessment of Van der Ham adhesion score based on adhesion formation around the anastomosis showed no significant difference ( p = 0.358; Jonckheere–Terpstra test) (B) . Stability was further studied by means of burst pressure; the difference between GM1 and GM2 was significant ( p = 0.02; Mann–Whitney U test), while no significant differences were observed compared with the control group (GM1 vs Control: p = 0.053; GM2 vs Control: p = 0.379) (C) . The location of rupture during burst pressure assessment showed no significant difference ( p > 0.05; Fisher–Freeman–Halton test) (D) . GM1: n = 7, GM2: n = 10, Control: n = 17. 3.2 Macroscopic Examination No AL or stenosis was observed in any group. All anastomoses were patent and free of stenosis. Adhesions were present in all groups, with variable severity ( Fig. 2A,B ; 3B ). In GM1, 14.3 % of anastomoses showed no adhesions, 28.6 % had mild adhesions (+1), 42.9 % moderate (+2), and 14.3 % severe (+3). In GM2, 20 % were adhesion-free, 10 % mild, 30 % moderate, and 40 % severe. In the control group, 17.6 % showed no adhesions, 5.9 % mild, 35.3 % moderate, and 41.2 % severe. Mild adhesions were more frequent in GM1, whereas severe adhesions predominated in GM2 and controls. Overall, differences in adhesion distribution among groups were not statistically significant (p = 0.358). 3.3 Anastomotic Burst Pressure Anastomotic burst pressure was highest in GM1 (193 ± 43.6 mmHg) and lowest in GM2 (155 ± 65.5 mmHg), compared with 167 ± 42.3 mmHg in the control group ( Fig. 3C ). The difference between GM1 and GM2 reached statistical significance (p = 0.02), whereas comparisons of GM1 or GM2 with controls were not significant (p = 0.053 and p = 0.379, respectively). In most cases, intestinal rupture occurred outside the anastomosis (71.4 % in GM1, 80 % in GM2, and 82.4 % in controls; p = 0.861; Fig. 3D ), with no notable differences between groups. 3.4 Histological Examination 78 specimens were submitted to histological examination and the anastomoses were visualized in 77 of these. Granulation tissue and fibroblast-rich fibrosis were found in all anastomoses, frequently in zonal arrangements and often surrounding residual surgical material ( Fig. 4 A, C ). However, differences between anastomoses were observed as follows and scored in a systematic slide review as present or absent: granulocytic inflammation adjacent to surgical material (GIS) ( Fig. 4 B, D ); abscess formation independent of residual surgical material (IAF) ; surgical induced mucosal hernias without abscess formation (HAS) , abscess formation in surgically induced mucosal hernias (HWA) ; purulent exudate on the peritoneum (PEP) . The slide review was done blinded to anastomosis types and the type of membrane (GM1 versus GM2). The results of the two slices per anastomosis were combined into one result, basing the final score on the more severe histological finding. GIS was found more frequently in the groups of the membranes, especially in group GM1 (GM1: 42.9 %, GM2: 30.0 % Control: 11.8 %; p = 0.221). PEP also occurred most frequently in GM1 and was least frequent in the control group (GM1: 42.9 %, GM2: 10.0 %, Control: 5.9 %; p = 0.076). In contrast, HWA was found exclusively in the control group ( Table 1 ). However, the differences between the three groups were not statistically significant. View this table: View inline View popup Download powerpoint Table 1: Results of the histological examination: granulocytic inflammation adjacent to surgical material (GIS) ; abscess formation independent of residual surgical material (IAF) ; surgical induced mucosal hernias without abscess formation (HAS) , abscess formation in surgically induced mucosal hernias (HWA) ; purulent exudate on the peritoneum (PEP) . The difference between the groups does not reach statistical significance (all p-values > 0.05; Fisher-Freeman-Halton test). Download figure Open in new tab Figure 4: Microscopic images of two anastomoses, both from group GM2: (A) Panoramic view of an anastomosis without significant granulocytic inflammation; (C) at higher magnification residual PDO substrate is seen (arrow) which is surrounded by a fibrosing reaction. (B) Panoramic view of an anastomosis with substantial granulocytic inflammation (scored GIS) around residual PDO substrate, which at higher magnification (D) is fully appreciated. 4 DISCUSSION 4.1 Principal Findings This study suggests that integration of a PDO membrane into stapled anastomoses does not impair anastomotic healing, supporting its potential as an intraanastomotic carrier membrane for sensor devices. GM1 exhibited slightly higher macroscopic healing performance than GM2, although this difference reached statistical significance only in burst pressure measurements. No group performed worse than comparable data reported in the literature 16 . All other macroscopic parameters were similar across the groups. Moderate to severe adhesions were observed in all groups. This design was deliberately chosen to minimize total animal use in accordance with the 3R principle. Comparable adhesion scores and the absence of significant intergroup differences suggest that the membrane itself did not substantially contribute to adhesion formation. Histological analysis indicated a higher frequency of granulocytic inflammation and purulent exudate in GM1 compared with GM2 ( Table 1 ), suggesting a modest local tissue response. However, these differences were not statistically significant and likely reflect a physiological reaction to resorbable material, without impacting anastomotic stability. PDO has a long history of clinical use as a suture and implant material, with well-established biocompatibility and predictable in vivo degradation kinetics 12 . This study confirms the mechanical stability of the membrane and its compatibility with standard surgical techniques. The membrane could be reliably introduced through the circular stapler without technical difficulty, and the stapler functioned normally with the membrane in place. Large spokes remained stable, supporting potential future circumferential sensing. The outer ring was largely intact, with a single break in GM2 resulting from moisture-related accelerated PDO 12 degradation due to non-airtight storage, which could be prevented with improved industrial packaging. Dislocation of small spokes occurred frequently but was not considered critical, as they primarily support implantation and are not intended for sensor integration. 4.2 Clinical Relevance and Translational Outlook AL is influenced by multiple factors, some modifiable intraoperatively (e.g., blood loss, fecal contamination, operative time), and others patient-specific (e.g., chronic kidney disease, diabetes, hypertension, smoking), which are prognostic for AL 20 – 24 . These factors often affect microvascular perfusion and wound healing, meaning not all AL can be prevented. Non– technically induced insufficiencies typically develop gradually, offering an opportunity for early detection prior to perforation or peritonitis. Currently, no clinical device provides real-time, direct monitoring of anastomotic healing. Radiologic methods, such as CT imaging, have limited sensitivity, as shown by Doeksen et al. 25 , 26 , and involve radiation exposure that should be avoided without clinical indication 26 , 27 . Endoscopic examination provides sufficient sensitivity and specificity but is invasive. Recent studies have explored bioresorbable sensors, including impedance-based systems 28 , magnesium electrodes 29 , and wireless oxygen or pH sensors 30 . However, these approaches generally provide only single-point measurements or require external positioning, limiting circumferential coverage. In contrast, the PDO membrane provides a mechanically stable, circumferential platform for potential site-specific sensing along the entire staple line. At the same time, several studies have already shown that impedance measurements can be used to recognize anastomotic insufficiencies at an early stage 31 , 32 . Previous ex vivo work demonstrated the feasibility of integrating resorbable electronic elements directly onto PDO membranes using screen-printable zinc and silver inks, confirming mechanical stability, biocompatibility, and controlled degradation 33 . Future studies will focus on incorporating sensors (impedance-, oxygen-, or lactate-based 34 – 36 ) onto the membrane surface to enable continuous, localized monitoring of anastomotic healing. The circumferential design may allow early detection of impaired healing, supporting timely intervention. From a translational perspective, the use of clinically established PDO and standard manufacturing techniques such as extrusion or thermoforming enables scalable, cost-efficient production of sensor-integrated membranes compatible with existing medical-grade polymers once sensor functionality and long-term safety have been validated. This study demonstrates that a bioresorbable PDO membrane can be safely integrated into stapler anastomoses in a porcine model without compromising anastomotic healing. The membrane provides a mechanically stable, biocompatible platform suitable for future development of smart anastomotic devices. 4.3 Limitations The obtained results are part of a proof-of-concept study; therefore, the sample size was not calculated by a power-analysis. To finally evaluate the influence on long-term anastomotic healing, a power analysis-based case-control study should be performed including extended clinical and histological follow-up. Consequently, the translational potential to human application remains preliminary. Future studies should address sensor material integration and prolonged observation periods. 5 Conclusion This proof-of-concept study demonstrates the technical feasibility of integrating a resorbable PDO membrane into stapled small bowel anastomoses without compromising anastomotic integrity, thereby highlighting its potential for future sensor integration. The results are encouraging, but further studies with larger cohorts and extended follow-up are required to confirm safety beyond a reasonable doubt. Data Availability All data produced in the present study are available upon reasonable request to the authors Conflict of Interest Authors D.W., F.J., D.F., E.G., H.K., J.H., S.H., C.S., K.L. declare to be inventors on patent number DE 10 2024 137 023.8, which is related to this script. Other authors declare no conflict of interest. Fundings This project is funded by the DFG – German Research Foundation under project number 461264398 and grant number SCHA 1686/6-1. The PDO-membrane substrate was provided free of charge by Ethicon ® , Inc., a Johnson & Johnson company, Somerville, NJ, USA. Acknowledgment We thank the staff of the Rudolf Zenker Institute for Experimental Surgery for their excellent animal care and valuable assistance in preparing the histological sections. We also gratefully acknowledge Ms. Burmeister for her support with graphic design and for taking photographs. RK thanks the Hector Fellow Academy for Funding and Support. References 1. ↵ Alanezi K and Urschel JD . Mortality secondary to esophageal anastomotic leak . Ann Thorac Cardiovasc Surg 2004 ; 10 : 71 – 75 . OpenUrl PubMed 2. Biere SSAY , Maas KW , Cuesta MA , et al. Cervical or thoracic anastomosis after esophagectomy for cancer: a systematic review and meta-analysis . Dig Surg 2011 ; 28 : 29 – 35 . OpenUrl CrossRef PubMed 3. ↵ Hogan BA , Winter DC , Broe D , et al. Prospective trial comparing contrast swallow, computed tomography and endoscopy to identify anastomotic leak following oesophagogastric surgery . Surg Endosc 2008 ; 22 : 767 – 771 . OpenUrl PubMed 4. ↵ Hammond J , Lim S , Wan Y , et al. The burden of gastrointestinal anastomotic leaks: an evaluation of clinical and economic outcomes . J Gastrointest Surg 2014 ; 18 : 1176 – 1185 , sciencedirect.com ( 2014 ). OpenUrl CrossRef PubMed 5. ↵ Schiff A , Roy S , Pignot M , et al. Diagnosis and Management of Intraoperative Colorectal Anastomotic Leaks: A Global Retrospective Patient Chart Review Study . Surg Res Pract 2017 ; 2017 : 3852731 . OpenUrl PubMed 6. Gessler B , Eriksson O and Angenete E. Diagnosis, treatment, and consequences of anastomotic leakage in colorectal surgery . Int J Colorectal Dis 2017 ; 32 : 549 – 556 , link.springer.com (2017). OpenUrl CrossRef PubMed 7. ↵ Chiarello MM , Fransvea P , Cariati M , et al. Anastomotic leakage in colorectal cancer surgery . Surgical Oncology 2022 ; 40 : 101708 , sciencedirect.com (2022). OpenUrl CrossRef PubMed 8. ↵ Ozata IH , Bozkurt E , Sucu S , et al. A novel scoring system for the early detection of anastomotic leakage: bedside leak score-a pilot study . Front Surg 2023 ; 10 : 1204785 . OpenUrl PubMed 9. ↵ Marres CCM , van de Ven AWH , Leijssen LGJ , et al. Colorectal anastomotic leak: delay in reintervention after false-negative computed tomography scan is a reason for concern . Tech Coloproctol 2017 ; 21 : 709 – 714 . OpenUrl PubMed 10. ↵ Komen N , Bruin RWF de , Kleinrensink GJ , et al. Anastomotic leakage, the search for a reliable biomarker. A review of the literature . Colorectal Dis 2008 ; 10 : 109 - 15 ; discussion 115-7. OpenUrl CrossRef PubMed 11. ↵ Fouda E , El Nakeeb A , Magdy A , et al. Early detection of anastomotic leakage after elective low anterior resection . J Gastrointest Surg 2011 ; 15 : 137 – 144 . OpenUrl PubMed 12. ↵ Martins JA , Lach AA , Morris HL , et al. Polydioxanone implants: A systematic review on safety and performance in patients . J Biomater Appl 2020 ; 34 : 902 – 916 . OpenUrl CrossRef PubMed 13. ↵ Mueller-Graf F , Merz J , Bandorf T , et al. Correlation of Pulse Wave Transit Time with Pulmonary Artery Pressure in a Porcine Model of Pulmonary Hypertension . Biomedicines 2021 ; 9 . 14. ↵ National Research Council . Guide for the care and use of laboratory animals . 8. ed. Washington, D.C .: National Academies Press , 2011 . 15. ↵ van der Ham AC , Kort WJ , Weijma IM , et al. Healing of ischemic colonic anastomosis: fibrin sealant does not improve wound healing . Dis Colon Rectum 1992 ; 35 : 884 – 891 . OpenUrl CrossRef PubMed 16. ↵ Giusto G , Vercelli C , Iussich S , et al. Comparison of the effects of platelet-rich or growth factor-rich plasma on intestinal anastomosis healing in pigs . BMC Vet Res 2017 ; 13 : 188 . OpenUrl PubMed 17. ↵ Witte MB , Saupe J , Reiner J , et al. Ileocolonic Healing after Small Ileocecal Resection in Mice: NOD2 Deficiency Impairs Anastomotic Healing by Local Mechanisms . J Clin Med 2023 ; 12 . 18. ↵ Pantelis D , Kabba MS , Kirfel J , et al. Transient perioperative pharmacologic inhibition of muscularis macrophages as a target for prophylaxis of postoperative ileus does not affect anastomotic healing in mice . Surgery 2010 ; 148 : 59 – 70 . OpenUrl PubMed 19. ↵ Verhofstad MH , Lange WP , van der Laak JA , et al. Microscopic analysis of anastomotic healing in the intestine of normal and diabetic rats . Dis Colon Rectum 2001 ; 44 : 423 – 431 . OpenUrl CrossRef PubMed Web of Science 20. ↵ Isohata N , Endo S , Nemoto T , et al. Risk Factors and Predictive Biomarkers for Anastomotic Leakage after Colorectal Cancer Surgery with the Double Stapling Technique . J Anus Rectum Colon 2023 ; 7 : 196 – 205 . OpenUrl PubMed 21. Leichtle SW , Mouawad NJ , Welch KB , et al. Risk factors for anastomotic leakage after colectomy . Dis Colon Rectum 2012 ; 55 : 569 – 575 . OpenUrl PubMed 22. van Kooten RT , Voeten DM , Steyerberg EW , et al. Patient-Related Prognostic Factors for Anastomotic Leakage, Major Complications, and Short-Term Mortality Following Esophagectomy for Cancer: A Systematic Review and Meta-Analyses . Ann Surg Oncol 2022 ; 29 : 1358 – 1373 . OpenUrl PubMed 23. Pommergaard H-C , Achiam MP , Burcharth J , et al. Impaired blood supply in the colonic anastomosis in mice compromises healing . Int Surg 2015 ; 100 : 70 – 76 . OpenUrl PubMed 24. ↵ Kruschewski M , Rieger H , Pohlen U , et al. Risk factors for clinical anastomotic leakage and postoperative mortality in elective surgery for rectal cancer . Int J Colorectal Dis 2007 ; 22 : 919 – 927 . OpenUrl CrossRef PubMed 25. ↵ Doeksen A , Tanis PJ , Wüst AFJ , et al. Radiological evaluation of colorectal anastomoses . Int J Colorectal Dis 2008 ; 23 : 863 – 868 . OpenUrl CrossRef PubMed 26. ↵ Nicksa GA , Dring RV , Johnson KH , et al. Anastomotic leaks: what is the best diagnostic imaging study? Dis Colon Rectum 2007 ; 50 : 197 – 203 . OpenUrl CrossRef PubMed 27. ↵ Bundy BD , Kauczor H-U and Grenacher L. Diagnostik und Definition der Nahtinsuffizienz aus radiologischer Sicht . Chirurg 2011 ; 82 : 56 – 67 . OpenUrl PubMed 28. ↵ Ben-David M , Carmeli I , Orgad R , et al. Implantation of an Impedance Sensor for Early Detection of Gastrointestinal Anastomotic Leaks . J Surg Res 2022 ; 278 : 49 – 56 . OpenUrl PubMed 29. ↵ Yang Y , Xiong X , Chen J , et al. Research advances in magnesium and magnesium alloys worldwide in 2020 . Journal of Magnesium and Alloys 2021 ; 9 : 705 – 747 , sciencedirect.com (2021). OpenUrl 30. ↵ Li S , Di Lu , Li S , et al. Bioresorbable, wireless, passive sensors for continuous pH measurements and early detection of gastric leakage . Sci Adv 2024 ; 10 : eadj0268 . OpenUrl PubMed 31. ↵ DeArmond DT , Carswell A , Louden CL , et al. Diagnosis of anastomotic leak: electrolyte detection versus barium fluoroscopy . J Surg Res 2013 ; 182 : 192 – 197 . OpenUrl PubMed 32. ↵ DeArmond DT , Cline AM and Johnson SB . Anastomotic leak detection by electrolyte electrical resistance . J Invest Surg 2010 ; 23 : 197 – 203 . OpenUrl PubMed 33. ↵ Jaekel F , Nair R , Teuerle L , et al. Exploring Polydioxanone as a Substrate for Fully Resorbable Implantable Sensors . Advanced Sensor Research 2025 . 34. ↵ Åkesson O , Abrahamsson P , Johansson G , et al. Surface microdialysis on small bowel serosa in monitoring of ischemia . J Surg Res 2016 ; 204 : 39 – 46 . OpenUrl PubMed 35. Hedberg J , Linder G and Sundbom M. Peri-anastomotic microdialysis lactate assessment after esophagectomy . Esophagus 2021 ; 18 : 783 – 789 . OpenUrl PubMed 36. ↵ Servais EL , Rizk NP , Oliveira L , et al. Real-time intraoperative detection of tissue hypoxia in gastrointestinal surgery by wireless pulse oximetry . Surg Endosc 2011 ; 25 : 1383 – 1389 . OpenUrl PubMed View the discussion thread. Back to top Previous Next Posted October 15, 2025. Download PDF Supplementary Material Data/Code Email Thank you for your interest in spreading the word about medRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following In Vivo Evaluation of a Biodegradable Intraanastomotic Membrane in a Porcine Model Message Subject (Your Name) has forwarded a page to you from medRxiv Message Body (Your Name) thought you would like to see this page from the medRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share In Vivo Evaluation of a Biodegradable Intraanastomotic Membrane in a Porcine Model Daniel C. Freund , Dennis Wahl , Eberhard Grambow , Finn Jaekel , Julia Henne , Richard Kantelberg , Hans Kleemann , Friedrich Prall , Amelie R. Zitzmann , Brigitte Vollmar , Jochen Hampe , Karl Leo , Sebastian Hinz , Clemens Schafmayer medRxiv 2025.10.10.25337726; doi: https://doi.org/10.1101/2025.10.10.25337726 Share This Article: Copy Citation Tools In Vivo Evaluation of a Biodegradable Intraanastomotic Membrane in a Porcine Model Daniel C. Freund , Dennis Wahl , Eberhard Grambow , Finn Jaekel , Julia Henne , Richard Kantelberg , Hans Kleemann , Friedrich Prall , Amelie R. Zitzmann , Brigitte Vollmar , Jochen Hampe , Karl Leo , Sebastian Hinz , Clemens Schafmayer medRxiv 2025.10.10.25337726; doi: https://doi.org/10.1101/2025.10.10.25337726 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Surgery Subject Areas All Articles Addiction Medicine (568) Allergy and Immunology (863) Anesthesia (299) Cardiovascular Medicine (4425) Dentistry and Oral Medicine (443) Dermatology (382) Emergency Medicine (607) Endocrinology (including Diabetes Mellitus and Metabolic Disease) (1507) Epidemiology (15221) Forensic Medicine (30) Gastroenterology (1123) Genetic and Genomic Medicine (6588) Geriatric Medicine (667) Health Economics (997) Health Informatics (4524) Health Policy (1368) Health Systems and Quality Improvement (1612) Hematology (540) HIV/AIDS (1264) Infectious Diseases (except HIV/AIDS) (15910) Intensive Care and Critical Care Medicine (1103) Medical Education (623) Medical Ethics (145) Nephrology (667) Neurology (6588) Nursing (346) Nutrition (998) Obstetrics and Gynecology (1143) Occupational and Environmental Health (956) Oncology (3331) Ophthalmology (970) Orthopedics (369) Otolaryngology (420) Pain Medicine (435) Palliative Medicine (129) Pathology (663) Pediatrics (1690) Pharmacology and Therapeutics (691) Primary Care Research (710) Psychiatry and Clinical Psychology (5440) Public and Global Health (9220) Radiology and Imaging (2195) Rehabilitation Medicine and Physical Therapy (1369) Respiratory Medicine (1196) Rheumatology (593) Sexual and Reproductive Health (710) Sports Medicine (529) Surgery (710) Toxicology (99) Transplantation (289) Urology (265) (function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'9ffdcbb22b35ad07',t:'MTc3OTQ3MzYxNQ=='};var a=document.createElement('script');a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();