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Kiseleva EB, Sovetsky AA, Ryabkov MG, Gubarkova EV, Plekhanov AA, Bederina EL, Potapov AL, Bogomolova AY, Zaitsev VY, Gladkova ND. Detecting emergence of ruptures in individual layers of the stretched intestinal wall using optical coherence elastography: A pilot study. JOURNAL OF BIOPHOTONICS 2024; 17:e202400086. [PMID: 38923316 DOI: 10.1002/jbio.202400086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 04/26/2024] [Accepted: 05/24/2024] [Indexed: 06/28/2024]
Abstract
We report a new application of compression optical coherence elastography (C-OCE) to monitor the emergence of ruptures in individual layers of longitudinally stretched small-intestine walls using tissue samples (n = 36) from nine minipigs. Before stretching, C-OCE successfully estimated stiffness for each intestine-wall layer: longitudinal muscular layer with serosa, circumferential muscular layer, submucosa and mucosa. In stretched samples, C-OCE clearly visualized initial stiffening in both muscular layers. By 25% elongation, a sharp stiffness decrease for the longitudinal muscular layer, indicated emergence of tears in all samples. With further stretching, for most samples, ruptures emerged in the circumferential muscular layer and submucosa, while mucosa remained undamaged. Histology confirmed the OCE-revealed damaging and absence of tissue damage for ~15% elongation. Thus, C-OCE has demonstrated a high potential for determining the safety tissue-stretching threshold which afterward may be used intraoperatively to prevent rupture risk in intestinal tissues stretched during various diagnostic/therapeutic procedures.
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Affiliation(s)
- Elena B Kiseleva
- Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod, Russia
| | - Alexander A Sovetsky
- Nonlinear Geophysical Processes Department, A.V. Gaponov-Grekhov Institute of Applied Physics of the Russian Academy of Sciences, Nizhny Novgorod, Russia
| | - Maksim G Ryabkov
- Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod, Russia
| | - Ekaterina V Gubarkova
- Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod, Russia
| | - Anton A Plekhanov
- Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod, Russia
| | - Evgeniya L Bederina
- University Clinic, Privolzhsky Research Medical University, Nizhny Novgorod, Russia
| | - Arseniy L Potapov
- Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod, Russia
| | - Alexandra Y Bogomolova
- Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod, Russia
| | - Vladimir Y Zaitsev
- Nonlinear Geophysical Processes Department, A.V. Gaponov-Grekhov Institute of Applied Physics of the Russian Academy of Sciences, Nizhny Novgorod, Russia
| | - Natalia D Gladkova
- Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod, Russia
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O’Quin C, Clayton SD, Trosclair L, Meyer H, Dao NH, Minagar A, White L, Welch V, Solitro G, Alexander JS, Sorrells D. Distraction Enterogenesis in Rats: A Novel Approach for the Treatment of Short Bowel Syndrome. PATHOPHYSIOLOGY 2024; 31:388-397. [PMID: 39189165 PMCID: PMC11348226 DOI: 10.3390/pathophysiology31030029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Revised: 06/13/2024] [Accepted: 07/22/2024] [Indexed: 08/28/2024] Open
Abstract
BACKGROUND Surgeons often encounter patients with intestinal failure due to inadequate intestinal length ("short bowel syndrome"/SBS). Treatment in these patients remains challenging and the process of physiologic adaptation may take years to complete, which frequently requires parenteral nutrition. We propose a proof-of-concept mechanical bowel elongation approach using a self-expanding prototype of an intestinal expansion sleeve (IES) for use in SBS to accelerate the adaptation process. METHODS IESs were deployed in the small intestines of Sprague Dawley rats. Mechanical characterization of these prototypes was performed. IES length-tension relationships and post-implant bowel expansion were measured ex vivo. Bowel histology before and after implantation was evaluated. RESULTS IES mechanical studies demonstrated decreasing expansive force with elongation. The deployment of IES devices produced an immediate 21 ± 8% increase in bowel length (p < 0.001, n = 11). Mechanical load testing data showed that the IESs expressed maximum expansive forces at 50% compression of the initial pre-contracted length. The small-intestine failure load in the rats was 1.88 ± 21 N. Intestinal histology post deployment of the IES showed significant expansive changes compared to unstretched bowel tissue. CONCLUSIONS IES devices were scalable to the rat intestinal model in our study. The failure load of the rat small intestine was many times higher than the force exerted by the contraction of the IES. Histology demonstrated preservation of intestinal structure with some mucosal erosion. Future in vivo rat studies on distraction enterogenesis with this IES should help to define this organogenesis phenomenon.
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Affiliation(s)
- Collyn O’Quin
- Department of Surgery, LSU Health Shreveport, Shreveport, LA 71103, USA; (C.O.); (S.D.C.); (L.T.)
| | - Sean D. Clayton
- Department of Surgery, LSU Health Shreveport, Shreveport, LA 71103, USA; (C.O.); (S.D.C.); (L.T.)
| | - Lexus Trosclair
- Department of Surgery, LSU Health Shreveport, Shreveport, LA 71103, USA; (C.O.); (S.D.C.); (L.T.)
| | - Hannah Meyer
- Department of Surgery, LSU Health Shreveport, Shreveport, LA 71103, USA; (C.O.); (S.D.C.); (L.T.)
| | - Nhi H. Dao
- Department of Molecular and Cellular Physiology, LSU Health Shreveport, Shreveport, LA 71103, USA (A.M.); (L.W.); (J.S.A.)
| | - Andrew Minagar
- Department of Molecular and Cellular Physiology, LSU Health Shreveport, Shreveport, LA 71103, USA (A.M.); (L.W.); (J.S.A.)
| | - Luke White
- Department of Molecular and Cellular Physiology, LSU Health Shreveport, Shreveport, LA 71103, USA (A.M.); (L.W.); (J.S.A.)
| | - Valerie Welch
- Department of Pathology, LSU Health Shreveport, Shreveport, LA 71103, USA;
| | - Giovanni Solitro
- Department of Orthopedic Surgery, LSU Health Shreveport, Shreveport, LA 71103, USA;
| | - Jonathan Steven Alexander
- Department of Molecular and Cellular Physiology, LSU Health Shreveport, Shreveport, LA 71103, USA (A.M.); (L.W.); (J.S.A.)
| | - Donald Sorrells
- Department of Surgery, LSU Health Shreveport, Shreveport, LA 71103, USA; (C.O.); (S.D.C.); (L.T.)
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Meyer H, Trosclair L, Clayton SD, O’Quin C, Crochet C, Colvin JC, Welch V, Alhaque A, Solitro G, Shah-Bruce M, Alexander JS, Sorrells DL. Histologic Analysis of 'Distraction Vaginogenesis' in a Rat Model. PATHOPHYSIOLOGY 2024; 31:298-308. [PMID: 38921727 PMCID: PMC11206798 DOI: 10.3390/pathophysiology31020022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 05/30/2024] [Accepted: 06/06/2024] [Indexed: 06/27/2024] Open
Abstract
Vaginal agenesis (VA) is frequently associated with mullerian agenesis. VA treatments include mechanical dilation and surgical vaginoplasty. We created a vaginal expansion sleeve (VES) as a novel device to progressively lengthen the vaginal canal. This study evaluated the histologic effects of the VES on rat vaginal tissue. The VES is a spring-like device made of proprietary woven cylindrical material and flat resin caps. The VESs were constructed as 25-30 mm, pre-contracted springs, which were secured into the vaginas of six Sprague Dawley rats and allowed to re-expand post-surgically. After one week, the VESs were removed, and the vaginas were harvested and measured in length. Test (n = 6) and control (n = 4) formalin-fixed paraffin-embedded tissues were stained with hematoxylin and eosin (H&E), Masson's trichrome, and anti-Desmin antibodies. The VESs achieved significant vaginal lengthening. The mean vaginal canal length increased from 20.0 ± 2.4 mm to 23.8 ± 1.2 mm after removal of the VESs (n = 6, p < 0.001), a 19% increase. There was a positive correlation between the expander/tension generated in the vagina and the amount of acute and chronic inflammation. H&E staining revealed increased submucosal eosinophilia in five of the six test tissues. One VES sample that was lengthened to 30 mm long showed evidence of lymphocytic and neutrophilic inflammation. Desmin immunostaining and Masson's trichrome stain revealed a thinner muscularis with more infiltrative fibrous tissue between muscle fibers in the test tissue compared to the control tissue. Although effective, the VES may provoke at least a transient increase in eosinophils consistent with a localized immune reaction during muscularis remodeling.
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Affiliation(s)
- Hannah Meyer
- Department of Surgery, LSU Health Shreveport, Shreveport, LA 71103, USA
| | - Lexus Trosclair
- Department of Surgery, LSU Health Shreveport, Shreveport, LA 71103, USA
| | - Sean D. Clayton
- Department of Surgery, LSU Health Shreveport, Shreveport, LA 71103, USA
| | - Collyn O’Quin
- Department of Surgery, LSU Health Shreveport, Shreveport, LA 71103, USA
| | - Carol Crochet
- Department of Surgery, LSU Health Shreveport, Shreveport, LA 71103, USA
| | - Joshua C. Colvin
- Department of Surgery, LSU Health Shreveport, Shreveport, LA 71103, USA
| | - Valerie Welch
- Department of Pathology, LSU Health Shreveport, Shreveport, LA 71103, USA
| | - Ahmed Alhaque
- Department of Molecular and Cellular Physiology, LSU Health Shreveport, Shreveport, LA 71103, USA (J.S.A.)
| | - Giovanni Solitro
- Department of Orthopedic Surgery, LSU Health Shreveport, Shreveport, LA 71103, USA
| | - Mila Shah-Bruce
- Department of Obstetrics and Gynecology, LSU Health Shreveport, Shreveport, LA 71103, USA
| | - J. Steven Alexander
- Department of Molecular and Cellular Physiology, LSU Health Shreveport, Shreveport, LA 71103, USA (J.S.A.)
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Hirsch TI, Wang SZ, Fligor SC, Quigley M, Gura KM, Puder M, Tsikis ST. Fat malabsorption in short bowel syndrome: A review of pathophysiology and management. Nutr Clin Pract 2024; 39 Suppl 1:S17-S28. [PMID: 38429962 PMCID: PMC10914324 DOI: 10.1002/ncp.11119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Revised: 11/13/2023] [Accepted: 12/28/2023] [Indexed: 03/03/2024] Open
Abstract
Fat malabsorption is central to the pathophysiology of short bowel syndrome (SBS). It occurs in patients with insufficient intestinal surface area and/or function to maintain metabolic and growth demands. Rapid intestinal transit and impaired bile acid recycling further contribute to fat malabsorption. A significant portion of patients require parenteral nutrition (PN) for their survival but may develop sepsis and liver dysfunction as a result. Despite advancements in the treatment of SBS, fat malabsorption remains a chronic issue for this vulnerable patient population. Peer-reviewed literature was assessed on the topic of fat malabsorption in SBS. Current management of patients with SBS involves dietary considerations, PN management, antidiarrheals, glucagon-like peptide 2 agonists, and multidisciplinary teams. Clinical trials have focused on improving intestinal fat absorption by facilitating fat digestion with pancreatic enzymes. Targeting fat malabsorption in SBS is a potential pathway to improving lifestyle and reducing morbidity and mortality in this rare disease.
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Affiliation(s)
- Thomas I. Hirsch
- Vascular Biology Program, Department of Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Sarah Z. Wang
- Vascular Biology Program, Department of Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Scott C. Fligor
- Vascular Biology Program, Department of Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Mikayla Quigley
- Vascular Biology Program, Department of Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Kathleen M. Gura
- Department of Pharmacy and the Division of Gastroenterology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Mark Puder
- Vascular Biology Program, Department of Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Savas T. Tsikis
- Vascular Biology Program, Department of Surgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA
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Hinnant T, Ning W, Lechler T. Compartment specific responses to contractility in the small intestinal epithelium. PLoS Genet 2024; 20:e1010899. [PMID: 38517900 PMCID: PMC10990186 DOI: 10.1371/journal.pgen.1010899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Revised: 04/03/2024] [Accepted: 03/07/2024] [Indexed: 03/24/2024] Open
Abstract
Tissues are subject to multiple mechanical inputs at the cellular level that influence their overall shape and function. In the small intestine, actomyosin contractility can be induced by many physiological and pathological inputs. However, we have little understanding of how contractility impacts the intestinal epithelium on a cellular and tissue level. In this study, we probed the cell and tissue-level effects of contractility by using mouse models to genetically increase the level of myosin activity in the two distinct morphologic compartments of the intestinal epithelium, the crypts and villi. We found that increased contractility in the villar compartment caused shape changes in the cells that expressed the transgene and their immediate neighbors. While there were no discernable effects on villar architecture or cell polarity, even low levels of transgene induction in the villi caused non-cell autonomous hyperproliferation of the transit amplifying cells in the crypt, driving increased cell flux through the crypt-villar axis. In contrast, induction of increased contractility in the proliferating cells of the crypts resulted in nuclear deformations, DNA damage, and apoptosis. This study reveals the complex and diverse responses of different intestinal epithelial cells to contractility and provides important insight into mechanical regulation of intestinal physiology.
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Affiliation(s)
- Taylor Hinnant
- Department of Dermatology, Duke University Medical Center, Durham, North Carolina United States of America
- Department of Cell Biology, Duke University Medical Center, Durham, North Carolina United States of America
| | - Wenxiu Ning
- Department of Dermatology, Duke University Medical Center, Durham, North Carolina United States of America
- Center for Life Sciences, School of Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases. Yunnan University, Kunming, China
| | - Terry Lechler
- Department of Dermatology, Duke University Medical Center, Durham, North Carolina United States of America
- Department of Cell Biology, Duke University Medical Center, Durham, North Carolina United States of America
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Hinnant T, Ning W, Lechler T. Compartment specific responses to contractility in the small intestinal epithelium. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.08.07.552224. [PMID: 37609300 PMCID: PMC10441304 DOI: 10.1101/2023.08.07.552224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/24/2023]
Abstract
Tissues are subject to multiple mechanical inputs at the cellular level that influence their overall shape and function. In the small intestine, actomyosin contractility can be induced by many physiological and pathological inputs. However, we have little understanding of how contractility impacts the intestinal epithelium on a cellular and tissue level. In this study, we probed the cell and tissue-level effects of contractility by using mouse models to genetically increase the level of myosin activity in the two distinct morphologic compartments of the intestinal epithelium, the crypts and villi. We found that increased contractility in the villar compartment caused shape changes in the cells that expressed the transgene and their immediate neighbors. While there were no discernable effects on villar architecture, even low levels of transgene induction in the villi caused non-cell autonomous hyperproliferation of the transit amplifying cells in the crypt, driving increased cell flux through the crypt-villar axis. In contrast, induction of increased contractility in the proliferating cells of the crypts resulted in nuclear deformations, DNA damage, and apoptosis. This study reveals the complex and diverse responses of different intestinal epithelial cells to contractility and provides important insight into mechanical regulation of intestinal physiology.
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Affiliation(s)
- Taylor Hinnant
- Department of Dermatology, Duke University Medical Center, Durham, NC 27710 USA
- Department of Cell Biology, Duke University Medical Center, Durham, NC 27710 USA
| | - Wenxiu Ning
- Department of Dermatology, Duke University Medical Center, Durham, NC 27710 USA
- Center for Life Sciences, School of Life Sciences, State Key Laboratory of Conservation and Utilization of Bio-resources in Yunnan, Yunnan University, Kunming 650500, China
| | - Terry Lechler
- Department of Dermatology, Duke University Medical Center, Durham, NC 27710 USA
- Department of Cell Biology, Duke University Medical Center, Durham, NC 27710 USA
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Meyer H, Trosclair L, Clayton SD, O’Quin C, Connelly Z, Rieger R, Dao N, Alhaque A, Minagar A, White LA, Solitro G, Shah-Bruce M, Welch VL, Villalba S, Alexander JS, Sorrells D. ‘Distraction Vaginogenesis’: Preliminary Results Using a Novel Method for Vaginal Canal Expansion in Rats. Bioengineering (Basel) 2023; 10:bioengineering10030351. [PMID: 36978742 PMCID: PMC10045428 DOI: 10.3390/bioengineering10030351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 03/04/2023] [Accepted: 03/07/2023] [Indexed: 03/16/2023] Open
Abstract
Vaginal atresia is seen in genetic disorders such as Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome, which can cause significant sexual dysfunction. Current treatments include surgical reconstruction or mechanical dilation of the vaginal canal. Mechanical dilation requires patients to be highly motivated and compliant while surgical reconstruction has high rates of complications. This study evaluated a novel vaginal expansion sleeve (VES) method as an alternative treatment for vaginal atresia. The proprietary cylindrical VES is a spring-like device consisting of polyethylene terephthalate helicoid trusses capped at each end with a fixed diameter resin cap for fixation within tissues. Following the development of the VES and mechanical characterization of the force–length relationships within the device, we deployed the VES in Sprague Dawley rat vaginas anchored with nonabsorbable sutures. We measured the VES length–tension relationships and post-implant vaginal canal expansion ex vivo. Vaginal histology was examined before and after implantation of the VES devices. Testing of 30 mm sleeves without caps resulted in an expansion force of 11.7 ± 3.4 N and 2.0 ± 0.1 N at 50% and 40%, respectively. The implanted 20 mm VES resulted in 5.36 mm ± 1.18 expansion of the vaginal canal, a 32.5 ± 23.6% increase (p = 0.004, Student t test). Histological evaluation of the VES implanted tissue showed a significant thinning of the vaginal wall when the VES was implanted. The novel VES device resulted in a significant expansion of the vaginal canal ex vivo. The VES device represents a unique alternative to traditional mechanical dilation therapy in the treatment of vaginal atresia and represents a useful platform for the mechanical distension of hollow compartments, which avoids reconstructive surgeries and progressive dilator approaches.
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Affiliation(s)
- Hannah Meyer
- Department of Surgery, LSU Health Shreveport, Shreveport, LA 71103, USA
| | - Lexus Trosclair
- Department of Surgery, LSU Health Shreveport, Shreveport, LA 71103, USA
| | - Sean D. Clayton
- Department of Surgery, LSU Health Shreveport, Shreveport, LA 71103, USA
| | - Collyn O’Quin
- Department of Surgery, LSU Health Shreveport, Shreveport, LA 71103, USA
| | - Zachary Connelly
- Department of Surgery, LSU Health Shreveport, Shreveport, LA 71103, USA
| | - Ross Rieger
- Department of Surgery, LSU Health Shreveport, Shreveport, LA 71103, USA
| | - Nhi Dao
- Department of Molecular and Cellular Physiology, LSU Health Shreveport, Shreveport, LA 71103, USA
| | - Ahmed Alhaque
- Department of Molecular and Cellular Physiology, LSU Health Shreveport, Shreveport, LA 71103, USA
| | - Andrew Minagar
- Department of Molecular and Cellular Physiology, LSU Health Shreveport, Shreveport, LA 71103, USA
| | - Luke A. White
- Department of Molecular and Cellular Physiology, LSU Health Shreveport, Shreveport, LA 71103, USA
| | - Giovanni Solitro
- Department of Orthopedic Surgery, LSU Health Shreveport, Shreveport, LA 71103, USA
| | - Mila Shah-Bruce
- Department of Obstetrics and Gynecology, LSU Health Shreveport, Shreveport, LA 71103, USA
| | - Valerie L. Welch
- Department of Pathology, LSU Health Shreveport, Shreveport, LA 71103, USA
| | - Stephanie Villalba
- Department of Biology, Louisiana State University in Shreveport, Shreveport, LA 71115, USA
| | | | - Donald Sorrells
- Department of Surgery, LSU Health Shreveport, Shreveport, LA 71103, USA
- Correspondence:
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Anderson TN, Mueller C, Dunn JC. Intestinal lengthening via mechanical enterogenesis in an infant with short gut syndrome. JOURNAL OF PEDIATRIC SURGERY CASE REPORTS 2023. [DOI: 10.1016/j.epsc.2023.102594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/02/2023] Open
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Zhou Z, Li K, Shi L, Wang Y, He Y, Hu W, Guo J. Self-Assembled Integrative Nutrient Carrier Platform Containing Green Tea Catechin for Short Bowel Syndrome Treatment. Adv Healthc Mater 2023; 12:e2201933. [PMID: 36337003 DOI: 10.1002/adhm.202201933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 09/28/2022] [Indexed: 11/09/2022]
Abstract
Extensive resection of the small intestine leads to the development of short bowel syndrome (SBS), which reduces the effective absorptive surface area of the intestine and predisposes patients to emaciation, malnutrition, and other severe symptoms. Herein, green tea catechin (-)-epigallocatechin gallate (EGCG) and ferrous ions (Fe2+ ) are utilized to construct a nutrient carrier platform that self-assembles with nutrients to form phenolic-based nutrient complexes (PNCs). PNCs effectively prolong the residence and absorption time of nutrients in the intestine. Further this platform is applied to integrate full nutrient formula, an enteral nutrition (EN) preparation containing a range of full nutrient components. In an SBS rat model, the prepared phenolic-based integrative nutrient complexes (PINCs) enhance nutritional status, improve anemia and immune function, as well as facilitate the growth of remaining intestinal villi and crypts, and maintain the integrity of the intestinal barrier. In addition, PINCs enable the modulation of gut microbial dysbiosis, enrich the abundance of beneficial bacteria, and have no toxic effects after the long-term ingestion. These results provide a proof of principle for the use of polyphenol-based nanocomplexes as EN preparation, offering a feasible strategy for both nutritional support and therapeutic perspectives for SBS treatment.
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Affiliation(s)
- Zhengming Zhou
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Ke Li
- Department of Clinical Nutrition, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Lei Shi
- Department of Clinical Nutrition, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Yunfeng Wang
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Yunxiang He
- BMI Center for Biomass Materials and Nanointerfaces, College of Biomass Science and Engineering, Sichuan University, Chengdu, Sichuan, 610065, China
| | - Wen Hu
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.,Department of Clinical Nutrition, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Junling Guo
- BMI Center for Biomass Materials and Nanointerfaces, College of Biomass Science and Engineering, Sichuan University, Chengdu, Sichuan, 610065, China.,Bioproducts Institute, Department of Chemical and Biological Engineering, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.,State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, Sichuan, 610065, China
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Surgical Treatment of Short Bowel Syndrome—The Past, the Present and the Future, a Descriptive Review of the Literature. CHILDREN 2022; 9:children9071024. [PMID: 35884008 PMCID: PMC9322125 DOI: 10.3390/children9071024] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 06/26/2022] [Accepted: 07/07/2022] [Indexed: 12/27/2022]
Abstract
Short bowel syndrome (SBS) is a devastating disorder with both short- and long-term implications for patients. Unfortunately, the prevalence of SBS has doubled over the past 40 years. Broadly speaking, the etiology of SBS can be categorized as congenital or secondary, the latter typically due to extensive small bowel resection following diseases of the small intestine, e.g., necrotizing enterocolitis, Hirschsprung’s disease or intestinal atresia. As of yet, no cure exists, thus, conservative treatment, primarily parenteral nutrition (PN), is the first-line therapy. In some cases, weaning from PN is not possible and operative therapy is required. The invention of the longitudinal intestinal lengthening and tailoring (LILT or Bianchi) procedure in 1980 was a major step forward in patient care and spawned further techniques that continue to improve lives for patients with severe SBS (e.g., double barrel enteroplasty, serial transverse enteroplasty, etc.). With this review, we aim to provide an overview of the clinical implications of SBS, common conservative therapies and the development of operative techniques over the past six decades. We also provide a short outlook on the future of operative techniques, specifically with respect to regenerative medicine.
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Biomechanical Force Prediction for Lengthening of Small Intestine during Distraction Enterogenesis. Bioengineering (Basel) 2020; 7:bioengineering7040140. [PMID: 33171760 PMCID: PMC7711478 DOI: 10.3390/bioengineering7040140] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 10/04/2020] [Accepted: 10/28/2020] [Indexed: 11/16/2022] Open
Abstract
Distraction enterogenesis has been extensively studied as a potential treatment for short bowel syndrome, which is the most common form of intestinal failure. Different strategies including parenteral nutrition and surgical lengthening to manage patients with short bowel syndrome are associated with high complication rates. More recently, self-expanding springs have been used to lengthen the small intestine using an intraluminal axial mechanical force, where this biomechanical force stimulates the growth and elongation of the small intestine. Differences in physical characteristics of patients with short bowel syndrome would require a different mechanical force—this is crucial in order to achieve an efficient and safe lengthening outcome. In this study, we aimed to predict the required mechanical force for each potential intestinal size. Based on our previous experimental observations and computational findings, we integrated our experimental measurements of patient biometrics along with mechanical characterization of the soft tissue into our numerical simulations to develop a series of computational models. These computational models can predict the required mechanical force for any potential patient where this can be advantageous in predicting an individual’s tissue response to spring-mediated distraction enterogenesis and can be used toward a safe delivery of the mechanical force.
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Hosseini HS, Wood LS, Taylor JS, Dubrovsky G, Portelli KI, Thomas AL, Dunn JC. Biomechanical signaling and collagen fiber reorientation during distraction enterogenesis. J Mech Behav Biomed Mater 2020; 101:103425. [DOI: 10.1016/j.jmbbm.2019.103425] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Revised: 08/16/2019] [Accepted: 09/09/2019] [Indexed: 12/11/2022]
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Hosseini HS, Taylor JS, Wood LS, Dunn JC. Biomechanics of small intestine during distraction enterogenesis with an intraluminal spring. J Mech Behav Biomed Mater 2020; 101:103413. [DOI: 10.1016/j.jmbbm.2019.103413] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2019] [Revised: 06/13/2019] [Accepted: 08/31/2019] [Indexed: 12/25/2022]
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Coletta R, Morabito A. Non-transplant Surgical Management of Short Bowel Syndrome in Children: An Overview. Curr Pediatr Rev 2019; 15:106-110. [PMID: 30499416 DOI: 10.2174/1573396315666181129164112] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Revised: 10/12/2018] [Accepted: 11/24/2018] [Indexed: 01/02/2023]
Abstract
Management of severe Short Bowel Syndrome (SBS) is still one of the largest challenges of the medicine. Vast majority of the short bowel patients are children, the conditions that lead to this possible outcome most often are necrotizing enterocolitis (NEC), small intestinal volvulus as a result of intestinal malrotation, gastroschisis and the "apple peel" syndrome. Therefore, paediatricians and paediatric surgeons face this challenge most often. The nontransplant treatment appears to be effective using surgical procedure to increase absorptive surface and to reduce the transit time, but in some cases these procedures are enough to weaning of TPN. The aim of this review was to summarize the modern non-stransplant surgical management of short bowel syndrome.
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Affiliation(s)
- Riccardo Coletta
- Department of Paediatric Surgery, Meyer Children's Hospital, University of Florence, Florence, Italy
| | - Antonino Morabito
- Department of Paediatric Surgery, Meyer Children's Hospital, University of Florence, Florence, Italy
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15
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Damian DD, Price K, Arabagi S, Berra I, Machaidze Z, Manjila S, Shimada S, Fabozzo A, Arnal G, Van Story D, Goldsmith JD, Agoston AT, Kim C, Jennings RW, Ngo PD, Manfredi M, Dupont PE. In vivo tissue regeneration with robotic implants. Sci Robot 2018; 3:3/14/eaaq0018. [DOI: 10.1126/scirobotics.aaq0018] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2017] [Accepted: 12/19/2017] [Indexed: 12/22/2022]
Affiliation(s)
- Dana D. Damian
- Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
- University of Sheffield, Sheffield S13JD, UK
| | - Karl Price
- Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Slava Arabagi
- Helbling Precision Engineering, Cambridge, MA 02142, USA
| | - Ignacio Berra
- National Pediatric Hospital J.P. Garrahan, Buenos Aires 01712, Argentina
| | - Zurab Machaidze
- Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Sunil Manjila
- McLaren Bay Neurosurgery Associates, Bay City, MI 48706, USA
| | | | | | - Gustavo Arnal
- Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - David Van Story
- Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
| | | | - Agoston T. Agoston
- Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Chunwoo Kim
- Korea Institute of Science and Technology, Seoul 02792, Republic of Korea
| | | | - Peter D. Ngo
- Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Michael Manfredi
- Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Pierre E. Dupont
- Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
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Zakhem E, Tamburrini R, Orlando G, Koch KL, Bitar KN. Transplantation of a Human Tissue-Engineered Bowel in an Athymic Rat Model. Tissue Eng Part C Methods 2017; 23:652-660. [PMID: 28653858 DOI: 10.1089/ten.tec.2017.0113] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Intestinal failure is a serious clinical condition characterized by loss of motility, absorptive function, and malnutrition. Current treatments do not provide the optimal solution for patients due to the numerous resulting complications. A bioengineered bowel that contains the necessary cellular components provides a viable option for patients. In this study, human tissue-engineered bowel (hTEB) was developed using a technique, whereby human-sourced smooth muscle cells were aligned and neoinnervated using human-sourced neural progenitor cells, resulting in the formation of intrinsically innervated smooth muscle sheets. The sheets were then rolled around hollow tubular chitosan scaffolds and implanted in the omentum of athymic rats for neovascularization. Four weeks later, biopsies of hTEB showed vascularization, normal cell alignment, phenotype, and function. During the biopsy procedure, hTEB was transplanted into the same rat's native intestine. The rats gained weight and 6 weeks later, hTEB was harvested for studies. hTEB was healthy in color with normal diameter and with digested food in the lumen, indicating propulsion of luminal content through the hTEB. Histological studies indicated neomucosa with evidence of crypts and villi structures. This study provides proof of concept that hTEB could provide a viable treatment to lengthen the gut for patients with gastrointestinal disorders.
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Affiliation(s)
- Elie Zakhem
- 1 Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine , Winston Salem, North Carolina.,2 Program in Neuro-Gastroenterology and Motility, Wake Forest School of Medicine , Winston Salem, North Carolina
| | - Riccardo Tamburrini
- 3 Department of Surgery, Wake Forest School of Medicine , Winston Salem, North Carolina.,4 Department of General Surgery, PhD program in Experimental Medicine, University of Pavia , Pavia, Italy
| | - Giuseppe Orlando
- 3 Department of Surgery, Wake Forest School of Medicine , Winston Salem, North Carolina
| | - Kenneth L Koch
- 2 Program in Neuro-Gastroenterology and Motility, Wake Forest School of Medicine , Winston Salem, North Carolina.,5 Section on Gastroenterology, Wake Forest School of Medicine , Winston Salem, North Carolina
| | - Khalil N Bitar
- 1 Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine , Winston Salem, North Carolina.,2 Program in Neuro-Gastroenterology and Motility, Wake Forest School of Medicine , Winston Salem, North Carolina.,5 Section on Gastroenterology, Wake Forest School of Medicine , Winston Salem, North Carolina.,6 Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Wake Forest School of Medicine , Winston Salem, North Carolina
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Abstract
PURPOSE OF REVIEW This review summarizes recent innovations in the treatment of patients with short bowel syndrome. RECENT FINDINGS The use of surgical procedures, growth factor stimulation, and bioengineering approaches to increase absorptive surface area of the intestine is examined. While the morphology of the intestine is clearly altered by these interventions, it is less clear that the overall function of the intestine is improved. SUMMARY Continued innovations will likely bring about new therapeutic options for patients with short bowel syndrome. Careful evaluations of the impact of these interventions await controlled clinical trials.
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Rouch JD, Huynh N, Scott A, Chiang E, Wu BM, Shekherdimian S, Dunn JCY. Scalability of an endoluminal spring for distraction enterogenesis. J Pediatr Surg 2016; 51:1988-1992. [PMID: 27665493 DOI: 10.1016/j.jpedsurg.2016.09.023] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2016] [Accepted: 09/12/2016] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Techniques of distraction enterogenesis have been explored to provide increased intestinal length to treat short bowel syndrome (SBS). Self-expanding, polycaprolactone (PCL) springs have been shown to lengthen bowel in small animal models. Their feasibility in larger animal models is a critical step before clinical use. METHODS Juvenile mini-Yucatan pigs underwent jejunal isolation or blind ending Roux-en-y jejunojejunostomy with insertion of either a PCL spring or a sham PCL tube. Extrapolated from our spring characteristics in rodents, proportional increases in spring constant and size were made for porcine intestine. RESULTS Jejunal segments with 7mm springs with k between 9 and 15N/m demonstrated significantly increased lengthening in isolated segment and Roux-en-y models. Complications were noted in only two animals, both using high spring constant k>17N/m. Histologically, lengthened segments in the isolated and Roux models demonstrated significantly increased muscularis thickness and crypt depth. Restoration of lengthened, isolated segments back into continuity was technically feasible after 6weeks. CONCLUSION Self-expanding, endoluminal PCL springs, which exert up to 0.6N force, safely achieve significant intestinal lengthening in a translatable, large-animal model. These spring characteristics may provide a scalable model for the treatment of SBS in children.
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Affiliation(s)
- Joshua D Rouch
- Department of Surgery, Division of Pediatric Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - Nhan Huynh
- Department of Surgery, Division of Pediatric Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - Andrew Scott
- Department of Surgery, Division of Pediatric Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - Elvin Chiang
- Department of Surgery, Division of Pediatric Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - Benjamin M Wu
- School of Engineering, Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - Shant Shekherdimian
- Department of Surgery, Division of Pediatric Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - James C Y Dunn
- Department of Surgery, Division of Pediatric Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA; School of Engineering, Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
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Strain induced esophageal growth in a novel rodent model. J Pediatr Surg 2016; 51:1273-8. [PMID: 26976775 DOI: 10.1016/j.jpedsurg.2016.01.014] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2015] [Revised: 01/09/2016] [Accepted: 01/11/2016] [Indexed: 10/22/2022]
Abstract
PURPOSE Longitudinal esophageal strain has been shown to increase esophageal length but the contribution of tissue hyperplasia to this growth is unknown. We used a novel model of esophageal stretch to determine the cellular response to the strain stimulus. METHODS Male Sprague-Dawley rats underwent transection of the distal esophagus. The distal stump was ligated and stretched over a silicone tube. The proximal esophageal stump was anastomosed to the stomach to restore continuity. After two, four, or seven days, the silicone tube was removed and the esophageal segment was measured and compared to its initial length. Sham animals had only a thin piece of silicone tubing placed. Standardized histologic sections were evaluated for wall thickness. Immunofluorescence with DAPI, Ki-67, and Myogenin antibodies was used to assess nuclear density, proliferation indices, and myoblast differentiation indices. RESULTS Experimental animals demonstrated a significant increase in esophageal length compared to sham controls at four and seven days with no difference at two days. There was significant lengthening between four and seven days among the experimental animals. There was no change in wall thickness between experimental and sham animals at any time point. Nuclear density was increased at all time points, although this only reached significance at day four. Proliferation indices were significantly increased relative to sham controls at all time points. Esophageal strain induced significantly increased myoblast differentiation. CONCLUSION In this novel rat model of esophageal strain, lengthening is associated with stable esophageal wall thickness, increased nuclear density, increased cellular proliferation, and increased myogenin expression. These data suggest that true tissue hyperplasia may contribute to the increased length seen after esophageal strain.
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20
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Rouch JD, Scott A, Jabaji ZB, Chiang E, Wu BM, Lee SL, Shekherdimian S, Dunn JCY. Basic fibroblast growth factor eluting microspheres enhance distraction enterogenesis. J Pediatr Surg 2016; 51:960-5. [PMID: 26995517 DOI: 10.1016/j.jpedsurg.2016.02.065] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2016] [Accepted: 02/26/2016] [Indexed: 12/12/2022]
Abstract
PURPOSE The purpose of this study was to determine if distraction enterogenesis using self-expanding polycaprolactone (PCL) springs is a potential therapy for short bowel syndrome. Sustained release basic fibroblast growth factor (bFGF) microspheres have been shown to induce angiogenesis and intestinal regeneration in tissue engineered scaffolds. We hypothesized that the provision of bFGF-loaded microspheres would increase angiogenesis and thereby enhance the process of enterogenesis. METHODS A 10-mm segment of rodent jejunum was isolated and an encapsulated PCL spring inserted. Blank or bFGF-loaded microspheres were delivered to the segment. After 4weeks, jejunal segments were assessed for lengthening, morphology, quantification of blood vessels, and ganglia. RESULTS Lengthened intestinal segments receiving bFGF microspheres demonstrated significantly increased microvascular density compared to those with blank microspheres. There were also significantly more submucosal and myenteric ganglia in the segments that received bFGF microspheres. Segments achieved similar lengthening and final muscular thickness in both blank and bFGF groups, but the bFGF microsphere caused a significant increase in luminal diameter of the jejunal segment. CONCLUSION Sustained release bFGF microspheres enhanced distraction enterogenesis through improved vascularity. The synergy of growth factors such as bFGF with distraction enterogenesis may yield improved results for the future treatment of patients with short bowel syndrome.
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Affiliation(s)
- Joshua D Rouch
- Department of Surgery, Division of Pediatric Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - Andrew Scott
- Department of Surgery, Division of Pediatric Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - Ziyad B Jabaji
- Department of Surgery, Division of Pediatric Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - Elvin Chiang
- Department of Surgery, Division of Pediatric Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - Benjamin M Wu
- School of Engineering, Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - Steven L Lee
- Department of Surgery, Division of Pediatric Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - Shant Shekherdimian
- Department of Surgery, Division of Pediatric Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - James C Y Dunn
- Department of Surgery, Division of Pediatric Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA; School of Engineering, Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
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21
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Scott A, Rouch JD, Huynh N, Chiang E, Shekherdimian S, Lee SL, Wu BM, Dunn JCY. Mechanical lengthening in multiple intestinal segments in-series. J Pediatr Surg 2016; 51:957-9. [PMID: 27013424 DOI: 10.1016/j.jpedsurg.2016.02.058] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Accepted: 02/26/2016] [Indexed: 11/26/2022]
Abstract
PURPOSE Current models of mechanical intestinal lengthening employ a single device in an isolated segment. Here we demonstrate that polycaprolactone (PCL) springs can be deployed in-series to lengthen multiple intestinal segments simultaneously to further increase overall intestinal length. METHODS A Roux-en-y jejunojejunostomy with a blind Roux limb was created in the proximal jejunum of rats. Two encapsulated 10-mm PCL springs were placed in-series into the Roux limb and were secured with clips. After 4weeks, the lengthened segments were retrieved for histological analyses. RESULTS Lengthening two intestinal segments simultaneously was achieved by placing two PCL springs in-series. The total combined length of the lengthened segments in-series was 45±4mm. The two jejunal segments with PCL springs (25±2 and 20±2mm) were significantly longer than control segments without the spring (14±1mm, p<0.05). CONCLUSION Spring-mediated lengthening can be achieved using multiple springs placed sequentially. The use of the Roux-en-y surgical model allowed easy insertion of springs in a blind Roux limb and arrange them in-series. Combined with relengthening techniques, we can use these methods to increase the length of small intestine to reach clinical significance. LEVEL OF EVIDENCE 1 Experimental.
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Affiliation(s)
- Andrew Scott
- Division of Pediatric Surgery, Department of Surgery, University of California, Los Angeles, CA, USA
| | - Joshua D Rouch
- Division of Pediatric Surgery, Department of Surgery, University of California, Los Angeles, CA, USA
| | - Nhan Huynh
- Division of Pediatric Surgery, Department of Surgery, University of California, Los Angeles, CA, USA
| | - Elvin Chiang
- Division of Pediatric Surgery, Department of Surgery, University of California, Los Angeles, CA, USA
| | - Shant Shekherdimian
- Division of Pediatric Surgery, Department of Surgery, University of California, Los Angeles, CA, USA
| | - Steven L Lee
- Division of Pediatric Surgery, Department of Surgery, University of California, Los Angeles, CA, USA
| | - Benjamin M Wu
- Department of Bioengineering, University of California, Los Angeles, CA, USA
| | - James C Y Dunn
- Division of Pediatric Surgery, Department of Surgery, University of California, Los Angeles, CA, USA; Department of Bioengineering, University of California, Los Angeles, CA, USA.
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22
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Demehri FR, Utter B, Freeman JJ, Fukatsu Y, Luntz J, Brei D, Teitelbaum DH. Development of an endoluminal intestinal attachment for a clinically applicable distraction enterogenesis device. J Pediatr Surg 2016; 51:101-6. [PMID: 26552895 PMCID: PMC4713322 DOI: 10.1016/j.jpedsurg.2015.10.026] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2015] [Accepted: 10/07/2015] [Indexed: 01/17/2023]
Abstract
PURPOSE Previous methods of distraction enterogenesis have relied upon blind-ending intestinal segments or transmural device fixation, requiring multiple operations and potential bowel injury. We hypothesized that using a novel attachment would allow reversible device coupling to the luminal bowel surface, achieving effective endoluminal distraction. METHODS A telescopic hydraulic device was designed with latex balloon attachments covered with high-friction mesh and a dilating fenestrated elastic mask (DFM attachment), allowing mesh-to-mucosa contact only with inflation. Yorkshire pigs underwent jejunal Roux-en-Y limb creation and device placement via jejunostomy. Devices underwent 3 cycles of balloon inflation and hydraulic extension/retraction per day for 7 days and then explanted and studied for efficacy. RESULTS DFM attachment allowed reversible, high-strength endoluminal coupling without tissue injury or reduction in bowel perfusion. After 7 day implant, distracted bowel achieved a 44 ± 2% increase in length vs. fed, nondistracted bowel, corresponding to a gain of 7.1 ± 0.3 cm. Distracted bowel demonstrated increased epithelial cell proliferation vs. control bowel. Attachment sites demonstrated villus flattening, increased crypt depth, thicker muscularis mucosa, and unchanged muscularis propria thickness vs. CONCLUSION Novel high-strength, reversible attachments enabled fully endoluminal distraction enterogenesis, achieving length gains comparable to open surgical techniques. This approach may allow development of clinically applicable technology for SBS treatment.
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Affiliation(s)
- Farokh R Demehri
- Section of Pediatric Surgery, Department of Surgery, University of Michigan, Ann Arbor, USA
| | - Brent Utter
- Department of Mechanical Engineering, University of Michigan, Ann Arbor, USA
| | - Jennifer J Freeman
- Section of Pediatric Surgery, Department of Surgery, University of Michigan, Ann Arbor, USA
| | - Yumi Fukatsu
- Section of Pediatric Surgery, Department of Surgery, University of Michigan, Ann Arbor, USA
| | - Jonathan Luntz
- Department of Mechanical Engineering, University of Michigan, Ann Arbor, USA
| | - Diann Brei
- Department of Mechanical Engineering, University of Michigan, Ann Arbor, USA
| | - Daniel H Teitelbaum
- Section of Pediatric Surgery, Department of Surgery, University of Michigan, Ann Arbor, USA.
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Zakhem E, Elbahrawy M, Orlando G, Bitar KN. Successful implantation of an engineered tubular neuromuscular tissue composed of human cells and chitosan scaffold. Surgery 2015; 158:1598-608. [PMID: 26096562 DOI: 10.1016/j.surg.2015.05.009] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2015] [Revised: 04/21/2015] [Accepted: 05/09/2015] [Indexed: 01/04/2023]
Abstract
BACKGROUND There is an urgent need for gut lengthening secondary to massive resections of the gastrointestinal tract. In this study, we propose to evaluate the remodeling, vascularization, and functionality of a chitosan-based, tubular neuromuscular tissue on subcutaneous implantation in the back of athymic rats. METHODS Aligned innervated smooth muscle sheets were bioengineered with the use of human smooth muscle and neural progenitor cells. The innervated sheets were wrapped around tubular chitosan scaffolds. The engineered tubular neuromuscular tissue was implanted subcutaneously in the back of athymic rats. The implant was harvested after 14 days and assessed for morphology, vascularization, and functionality. RESULTS Gross examination of the implants showed healthy color with no signs of inflammation. The implanted tissue became vascularized as demonstrated by gross and histologic analysis. Chitosan supported the luminal patency of the tissue. The innervated muscle remodeled around the tubular chitosan scaffold. Smooth muscle maintained its circumferential alignment and contractile phenotype. The functionality of the implant was characterized further by the use of real-time force generation. A cholinergic response was demonstrated by robust contraction in response to acetylcholine. Vasoactive intestinal peptide-, and electrical field stimulation-caused relaxation. In the presence of neurotoxin tetrodotoxin, the magnitude of acetylcholine-induced contraction and vasoactive intestinal peptide-induced relaxation was attenuated whereas electrical field stimulation-induced relaxation was completely abolished, indicating neuronal contribution to the response. CONCLUSION Our results indicated the successful subcutaneous implantation of engineered tubular neuromuscular tissues. The tissues became vascularized and maintained their myogenic and neurogenic phenotype and function, which provides potential therapeutic prospects for providing implantable replacement GI segments for treating GI motility disorders.
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Affiliation(s)
- Elie Zakhem
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston Salem, NC; Department of Molecular Medicine and Translational Sciences, Wake Forest School of Medicine, Winston Salem, NC
| | - Mostafa Elbahrawy
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston Salem, NC
| | - Giuseppe Orlando
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston Salem, NC
| | - Khalil N Bitar
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston Salem, NC; Department of Molecular Medicine and Translational Sciences, Wake Forest School of Medicine, Winston Salem, NC; Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Winston Salem, NC.
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Scott A, Sullins VF, Steinberger D, Rouch JD, Wagner JP, Chiang E, Lee SL, Wu BM, Dunn JCY. Repeated mechanical lengthening of intestinal segments in a novel model. J Pediatr Surg 2015; 50:954-7. [PMID: 25818320 DOI: 10.1016/j.jpedsurg.2015.03.020] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2015] [Accepted: 03/10/2015] [Indexed: 11/25/2022]
Abstract
PURPOSE Currently, animal models used for mechanical intestinal lengthening utilize a single lengthening procedure prior to analysis or restoration back into continuity. Here we developed a novel surgical model to examine the feasibility of repeated lengthening of intestinal segments. METHODS A Roux-en-Y jejunojejunostomy with a blind Roux limb was created in rats. An encapsulated polycaprolactone spring was placed into a 1cm segment of the Roux limb. After 4 weeks, a second encapsulated PCL spring was inserted into a 1cm portion of the lengthened segment. After another 4 weeks, the repeatedly lengthened segments were retrieved for histological analyses. RESULTS Jejunal segments of the Roux limb were successfully lengthened from 1.0 cm to 2.6 ± 0.7 cm. Four weeks after the second PCL spring placement, 1.0 cm of the previously lengthened segment increased to 2.7 ± 0.8 cm. Stronger mechanical force was required to achieve subsequent re-lengthening. Lengthened and re-lengthened segments had increased smooth muscle thickness and crypt depth when compared to normal jejunal mucosa. CONCLUSION Using the Roux-en-Y model, previously lengthened segments of intestine can be successfully re-lengthened. Intestinal segments may be subjected to multiple lengthening procedures to achieve clinically significant length for the treatment of short bowel syndrome.
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Affiliation(s)
- Andrew Scott
- Division of Pediatric Surgery, Department of Surgery, University of California, Los Angeles, CA, USA
| | - Veronica F Sullins
- Division of Pediatric Surgery, Department of Surgery, University of California, Los Angeles, CA, USA
| | - Doug Steinberger
- Department of Bioengineering, University of California, Los Angeles, CA, USA
| | - Joshua D Rouch
- Division of Pediatric Surgery, Department of Surgery, University of California, Los Angeles, CA, USA
| | - Justin P Wagner
- Division of Pediatric Surgery, Department of Surgery, University of California, Los Angeles, CA, USA
| | - Elvin Chiang
- Division of Pediatric Surgery, Department of Surgery, University of California, Los Angeles, CA, USA
| | - Steven L Lee
- Division of Pediatric Surgery, Department of Surgery, University of California, Los Angeles, CA, USA
| | - Benjamin M Wu
- Department of Bioengineering, University of California, Los Angeles, CA, USA
| | - James C Y Dunn
- Division of Pediatric Surgery, Department of Surgery, University of California, Los Angeles, CA, USA; Department of Bioengineering, University of California, Los Angeles, CA, USA.
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25
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Demehri FR, Freeman JJ, Fukatsu Y, Luntz J, Teitelbaum DH. Development of an endoluminal intestinal lengthening device using a geometric intestinal attachment approach. Surgery 2015; 158:802-11. [PMID: 26008962 DOI: 10.1016/j.surg.2015.03.055] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2015] [Revised: 03/30/2015] [Accepted: 03/31/2015] [Indexed: 02/08/2023]
Abstract
BACKGROUND Distraction enterogenesis may provide a novel therapy for short bowel syndrome. Previously described methods have relied on isolated intestinal segments or transmural fixation because of ineffective endoluminal attachment. We hypothesized that a novel approach of geometric coupling between a tapering device and the mesenteric curvature would allow trans-stomal distraction enterogenesis. METHODS A catheter device was designed with tapering stiffness, consisting of a stiff catheter with a taper to a flexible latex tip to prevent perforation. Yorkshire pigs underwent creation of a jejunal Roux limb with device placed via jejunostomy. Intestinal attachment was achieved without a substantial decrease in bowel perfusion as measured by laser Doppler. An external clamp was secured at the stoma to provide external fixation of the device. The catheter was advanced 1 cm/day for either 7 or 14 days before explant. RESULTS After 7 days, the distracted segment achieved a mean ± SD increase in length of 37 ± 6% versus fed, nondistracted bowel, corresponding to an absolute gain of 10.6 ± 1.7 cm (1.5 cm/day). After 14 days, the Roux limb achieved an 80 ± 2% increase in length versus fed control bowel, corresponding to an absolute gain of 16.8 ± 3.0 cm (1.2 cm/day). No perforation or stoma-related complication occurred. CONCLUSION We describe a novel catheter device with tapering stiffness allowing for endoluminal distraction enterogenesis via geometric coupling. This approach may allow development of clinically applicable technology for the treatment of patients with short bowel syndrome.
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Affiliation(s)
- Farokh R Demehri
- Section of Pediatric Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI
| | - Jennifer J Freeman
- Section of Pediatric Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI
| | - Yumi Fukatsu
- Section of Pediatric Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI
| | - Jonathan Luntz
- Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI
| | - Daniel H Teitelbaum
- Section of Pediatric Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI.
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26
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A novel double-balloon catheter device for fully endoluminal intestinal lengthening. Pediatr Surg Int 2014; 30:1223-9. [PMID: 25319796 DOI: 10.1007/s00383-014-3612-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/07/2014] [Indexed: 10/24/2022]
Abstract
OBJECTIVE Distraction enterogenesis may provide a novel therapy for short bowel syndrome (SBS). Previously described methods have relied upon isolated intestinal segments or transmural fixation. Our objective was to develop a novel, fully endoluminal device, permitting placement and removal through an enteral stoma or orifice. METHODS A flexible device was designed consisting of two latex balloons mounted on coaxial catheters. The inner catheter allowed longitudinal force transmission from an external spring. Yorkshire pigs underwent jejunal Roux limb creation with device placement via jejunostomy. Balloons were inflated to 52 mmHg without significant reduction in bowel perfusion as measured by laser Doppler. The device was explanted after 7 days. RESULTS Distracted bowel achieved an increase in length of 26.1 ± 6.1 % vs nondistracted fed bowel. As the device resided in unfed bowel, a 66.7 ± 14.5% increase vs unfed bowel was noted. These corresponded to a gain of 6.3 ± 2.3 cm (0.9 ± 0.3 cm/day) and 12.9 ± 7.6 cm (1.8 ± 1.1 cm/day), respectively. Attachment sites demonstrated occasional epithelial sloughing with no balloon-associated perforation. CONCLUSION A novel double-balloon catheter device allows for fully endoluminal distraction enterogenesis. This approach may allow development of clinically applicable technology for the treatment of patients with SBS.
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Sullins VF, Wagner JP, Walthers CM, Chiang EK, Lee SL, Wu BM, Dunn JCY. Function of mechanically lengthened jejunum after restoration into continuity. J Pediatr Surg 2014; 49:971-4; discussion 974-5. [PMID: 24888845 DOI: 10.1016/j.jpedsurg.2014.01.033] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2014] [Accepted: 01/27/2014] [Indexed: 11/30/2022]
Abstract
PURPOSE Distraction enterogenesis is a potential treatment for patients with short bowel syndrome. We previously demonstrated successful lengthening of jejunum using a degradable spring device in rats. Absorptive function of the lengthened jejunum after restoration into intestinal continuity needs to be determined. METHODS Encapsulated polycaprolactone springs were placed into isolated jejunal segments in rats for four weeks. Lengthened segments of jejunum were subsequently restored into intestinal continuity. Absorption studies were performed by placing a mixture of a non-absorbable substrate and glucose into the lumen of the restored jejunum. RESULTS Restored jejunal segments demonstrated visible peristalsis at specimen retrieval. Compared to normal jejunal controls, restored segments demonstrated equal water absorption and greater glucose absorption. Restored segments had thicker smooth muscle, increased villus height, increased crypt depth, and decreased sucrase activity compared to normal jejunum. The density of enteric ganglia increased after restoration to near normal levels in the submucosa and to normal levels in the myenteric plexus. CONCLUSION Jejunum lengthened with a degradable device demonstrates peristaltic and enzymatic activity as well as glucose and water absorption after restoration into intestinal continuity. Our findings further demonstrate the therapeutic potential of a degradable device.
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Affiliation(s)
- Veronica F Sullins
- Department of Surgery, Division of Pediatric Surgery, University of California, Los Angeles, Los Angeles, CA 90095-1749, USA
| | - Justin P Wagner
- Department of Surgery, Division of Pediatric Surgery, University of California, Los Angeles, Los Angeles, CA 90095-1749, USA
| | - Christopher M Walthers
- Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095-7098, USA
| | - Elvin K Chiang
- Department of Surgery, Division of Pediatric Surgery, University of California, Los Angeles, Los Angeles, CA 90095-1749, USA
| | - Steven L Lee
- Department of Surgery, Division of Pediatric Surgery, University of California, Los Angeles, Los Angeles, CA 90095-1749, USA
| | - Benjamin M Wu
- Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095-7098, USA
| | - James C Y Dunn
- Department of Surgery, Division of Pediatric Surgery, University of California, Los Angeles, Los Angeles, CA 90095-1749, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095-7098, USA.
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Sullins VF, Wagner JP, Suwarnasarn AT, Lee SL, Wu BM, Dunn JCY. A novel biodegradable device for intestinal lengthening. J Pediatr Surg 2014; 49:109-13; discussion 113. [PMID: 24439592 DOI: 10.1016/j.jpedsurg.2013.09.040] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2013] [Accepted: 09/30/2013] [Indexed: 11/20/2022]
Abstract
PURPOSE Previous studies demonstrated successful mechanical lengthening of rat jejunum using an encapsulated Nitinol spring device over a stabilizing guidewire. We sought to improve the applicability of intestinal lengthening by creating a biodegradable device. METHODS Using properties of the Nitinol spring device, polycaprolactone (PCL) springs with similar outer diameter and spring constant were created. After in vitro testing in dry and hydrated environments, they were used to lengthen 1-cm isolated segments of rat jejunum in vivo. Retrieved segments were analyzed histologically. RESULTS Optimal PCL spring devices had an average spring constant 1.8 ± 0.4 N/m, pitch 1.55 ± 0.85 mm, and band width 0.825 ± 0.016 mm. In vitro testing demonstrated stable spring constants. Jejunal segments were lengthened from 1.0 cm to 2.7 ± 0.4 cm without needing a stabilizing guidewire. Histology demonstrated increased smooth muscle thickness and fewer ganglia compared to controls. Lengthened jejunum was successfully restored into intestinal continuity and demonstrated peristalsis under fluoroscopy. CONCLUSIONS A novel biodegradable spring device was successfully created and used to mechanically lengthen intestinal segments. Use of a biodegradable device may obviate the need for retrieval after lengthening. This improves device applicability and may be useful for the treatment of short bowel syndrome.
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Affiliation(s)
- Veronica F Sullins
- Department of Surgery, Division of Pediatric Surgery, University of California, Los Angeles, Los Angeles, CA 90095-1749, USA
| | - Justin P Wagner
- Department of Surgery, Division of Pediatric Surgery, University of California, Los Angeles, Los Angeles, CA 90095-1749, USA
| | - Arnold T Suwarnasarn
- Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095-7098, USA
| | - Steven L Lee
- Department of Surgery, Division of Pediatric Surgery, University of California, Los Angeles, Los Angeles, CA 90095-1749, USA
| | - Benjamin M Wu
- Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095-7098, USA
| | - James C Y Dunn
- Department of Surgery, Division of Pediatric Surgery, University of California, Los Angeles, Los Angeles, CA 90095-1749, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095-7098, USA.
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Sueyoshi R, Woods Ignatoski KM, Okawada M, Teitelbaum DH. Distraction-induced intestinal growth: the role of mechanotransduction mechanisms in a mouse model of short bowel syndrome. Tissue Eng Part A 2013; 20:830-41. [PMID: 24070252 DOI: 10.1089/ten.tea.2013.0383] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Novel strategies are needed to address the problem of patients with short bowel syndrome. We previously demonstrated a three-fold lengthening of pig bowel after 2 weeks of applied distractive forces, but we have not elucidated the mechanisms facilitating this growth. We used a mouse model of distraction-induced enterogenesis. High molecular weight polyethylene glycol (PEG) osmotically stretched an isolated small bowel segment (PEG-stretch). Significant increases in villus height and crypt depth and in intestinal epithelial cell length and numbers suggested epithelial remodeling in addition to proliferation during enterogenesis. LC-MS/MS analysis showed a two-fold upregulation of α-actinin-1 and -4. We also demonstrated that p-focal adhesion kinase (FAK), FAK, α-actinin, and Rac1 were significantly upregulated and that F-actin was relocalized in PEG-stretch versus controls. Blockade of the phosphotidyl inositol 3' kinase pathway failed to influence the increase in proliferation or decline in apoptosis after stretch, suggesting alternative signaling pathways are used, including MEK and P38MAPK, which were both upregulated during enterogenesis. Our data suggests that several known mechanotransduction pathways drive distraction-induced enterogenesis.
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Affiliation(s)
- Ryo Sueyoshi
- Section of Pediatric Surgery, Department of Surgery, University of Michigan Health System , Ann Arbor, Michigan
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Sueyoshi R, Ralls MW, Teitelbaum DH. Glucagon-like peptide 2 increases efficacy of distraction enterogenesis. J Surg Res 2013; 184:365-73. [PMID: 23639355 DOI: 10.1016/j.jss.2013.03.089] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2013] [Revised: 03/22/2013] [Accepted: 03/27/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND Application of distractive forces to small bowel induces intestinal growth, or enterogenesis. This emerging area of research may provide treatment for short bowel syndrome. Glucagon-like peptide 2(GLP-2) has also been reported to induce small bowel growth after bowel resection. We hypothesized that exogenous GLP-2 will result in enhanced distraction-induced enterogenesis. METHODS Distraction-induced model was performed in 10-wk-old C57BL/6 mice using osmotic forces with high molecular weight polyethylene glycol (PEG)-stretch. Four groups were studied: Control group (PEG-/GLP-2-); PEG-stretch (PEG+/GLP-2-); GLP-2 control (PEG-/GLP-2+); and GLP-2 stretch (PEG+/GLP-2+). GLP-2 was given via subcutaneous osmotic pump over the 5 d of experiment. Morphology was measured by histomicrography. Epithelial cell (EC) proliferation was measured with proliferating cell nuclear antigen immunofluorescent staining. Total intestinal growth and blood vessel volume was assessed with Micro computed tomography volumetry. Vascular endothelial growth factor, fibroblast growth factor 1 and 2, and platelet-derived growth factor were measured by reverse-transcriptase polymerase chain reaction. RESULTS EC proliferation increased significantly in all groups compared with controls, but was greatest in the GLP-2 stretch group. Diameter and length significantly increased in the PEG-stretch and GLP-2 stretch groups. Moreover, there was statistically greater diameter, crypt depth and EC proliferation in the GLP-2 stretch versus PEG-stretch groups. GLP-2 stretch vessel volume was greater than all other groups and was significantly increased compared with controls. The relative expression of platelet-derived growth factor increased significantly in the PEG-stretch group versus the Control group. CONCLUSIONS GLP-2 had an additive effect on EC proliferation, tissue growth, histomorphology, and vascularization. We also demonstrated a unique action of GLP-2, the enhancement of intestinal vascularization. The combination of enterogenesis and GLP-2 may yield an improved approach to treat short bowel syndrome.
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Affiliation(s)
- Ryo Sueyoshi
- Section of Pediatric Surgery, Department of Surgery, University of Michigan, Mott Children's Hospital, Ann Arbor, Michigan 48109-4211, USA
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Ralls MW, Sueyoshi R, Herman R, Utter B, Czarnocki I, Luntz J, Brei D, Teitelbaum DH. Development of a novel approach to safely couple the intestine to a distraction-induced device for intestinal growth: use of reconstructive tissue matrix. Pediatr Surg Int 2013; 29:151-6. [PMID: 23108982 PMCID: PMC3557585 DOI: 10.1007/s00383-012-3198-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND Distraction-induced intestinal growth may be a novel treatment for short bowel syndrome. Longitudinal, distractive tension created by the application of force creates a significant challenge: to produce adequate force, yet not cause perforation at the fixation points. This paper describes our development of a coupling strategy to allow for successful bowel lengthening. METHODS A curvilinear hydraulic device was implanted in an isolated Roux limb of small bowel in young Yorkshire pigs. Bowel was lengthened over a 2-week period. Study groups included: Group 1: Twelve silk transmural anchoring sutures into an engineered-coupling ring at the ends of each device. Group 2: Addition of felt pledgets to the coupling rings on the serosal surface of the small bowel. Group 3: Extraluminal use of either thin AlloDerm(®), thick AlloDerm(®), or Strattice™ mesh to anchor the device. RESULTS Group 1 (suture-only) resulted in a gradual pulling through the suture with increasing tension and no lengthening. Felt pledgets eroded in a similar fashion, causing abdominal sepsis. Thin AlloDerm(®) failed to prevent erosion; however, it protected against gross contamination. Animals in which either thick AlloDerm(®) or Strattice™ mesh was used survived complication free to the study endpoint. Both thick AlloDerm(®) and Strattice™ prevented erosion and perforation allowing for an average of 10.85 cm expansion. CONCLUSION This study demonstrates the use of either thick AlloDerm(®) or Strattice™ reconstructive tissue matrix which allows for safe and effective coupling. Further, we suggest this approach could be an adjunct to esophageal lengthening procedures.
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Affiliation(s)
- Matthew W. Ralls
- Section of Pediatric Surgery, Department of Surgery and the C.S. Mott Children’s Hospital, University of Michigan, Ann Arbor, Michigan
| | - Ryo Sueyoshi
- Section of Pediatric Surgery, Department of Surgery and the C.S. Mott Children’s Hospital, University of Michigan, Ann Arbor, Michigan
| | - Richard Herman
- Section of Pediatric Surgery, Department of Surgery and the C.S. Mott Children’s Hospital, University of Michigan, Ann Arbor, Michigan
| | - Brent Utter
- Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan
| | - Isabel Czarnocki
- Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan
| | - Jonathan Luntz
- Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan
| | - Diann Brei
- Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan
| | - Daniel H. Teitelbaum
- Section of Pediatric Surgery, Department of Surgery and the C.S. Mott Children’s Hospital, University of Michigan, Ann Arbor, Michigan
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Jabaji Z, Stark R, Dunn JCY. Regeneration of enteric ganglia in mechanically lengthened jejunum after restoration into intestinal continuity. J Pediatr Surg 2013; 48:118-23. [PMID: 23331803 DOI: 10.1016/j.jpedsurg.2012.10.027] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2012] [Accepted: 10/13/2012] [Indexed: 01/28/2023]
Abstract
PURPOSE We previously demonstrated that it is feasible to lengthen intestinal segments with mechanical force and to restore them back into intestinal continuity. The changes in the enteric ganglia in the lengthened intestinal segments have not been described. METHODS A 1-cm segment of rodent jejunum was isolated from intestinal continuity and was lengthened using a spring. After lengthening, jejunal segments were either retrieved (n=4) or restored into intestinal continuity (n=4). Rats with restored segments were euthanized 2 to 3 weeks later. Ganglia were identified and quantified by immunostaining of histological sections. RESULTS The normal jejunum had 51 ± 5 myenteric and 31 ± 2 submucosal ganglia per circumferential tissue section. Lengthened segments had 21 ± 7 myenteric and 2 ± 2 submucosal ganglia. Restored segments had 46 ± 14 myenteric and 10 ± 10 submucosal ganglia. Circumferential density of ganglia followed a similar pattern. CONCLUSION Mechanical lengthening led to a paucity of submucosal and myenteric ganglia. After restoration into continuity, the number increased toward normal, indicating regeneration of the enteric ganglia. The function of regenerated ganglia needs to be assessed in the future.
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Affiliation(s)
- Ziyad Jabaji
- Department of Surgery, Division of Pediatric Surgery, University of California, Los Angeles, Los Angeles, CA 90095-1749, USA
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Ralls MW, Sueyoshi R, Herman RS, Utter B, Czarnocki I, Si N, Luntz J, Brei D, Teitelbaum DH. Mesenteric neovascularization with distraction-induced intestinal growth: enterogenesis. Pediatr Surg Int 2013; 29:33-9. [PMID: 23229341 PMCID: PMC3536931 DOI: 10.1007/s00383-012-3204-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
BACKGROUND Distraction-induced enterogenesis, whereby the intestine lengthens with application of linear forces, is an emerging area which may provide a unique treatment for short bowel syndrome. With an increase in overall tissue mass, there is an increase in oxygen and nutrient demand. We hypothesized that a neovascularization within the mesentery is necessary to support the growing small bowel. METHODS A curvilinear hydraulic device was used to induce growth within the small bowel of Yorkshire pigs, and the intestine was harvested after 14 days. High-resolution gross pictures were recorded of the mesentery at implantation and at harvest, and CT imaging of the bowel and mesentery was performed at harvest after dye injection. RESULTS After 2 weeks of distraction, an average of 72.5 % (8.7 cm) bowel lengthening was achieved. Gross images of the mesentery between major vessels showed a blossoming of the microvasculature and this was confirmed by CT imaging with 3D reconstruction. Mesenteric sample taken from the distracted segment had a fourfold increase in the volume of microvasculature versus controls. CONCLUSION Enterogenesis results not only in increased bowel length, but also significant increase in the mesenteric microvascularity. Presumably, this sustains the lengthened segment after application of longitudinal forces.
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Affiliation(s)
- Matthew W. Ralls
- Section of Pediatric Surgery, Department of Surgery and the C.S. Mott Children’s Hospital, University of Michigan, Ann Arbor, Michigan
| | - Ryo Sueyoshi
- Section of Pediatric Surgery, Department of Surgery and the C.S. Mott Children’s Hospital, University of Michigan, Ann Arbor, Michigan
| | - Richard S. Herman
- Section of Pediatric Surgery, Department of Surgery and the C.S. Mott Children’s Hospital, University of Michigan, Ann Arbor, Michigan
| | - Brent Utter
- Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan
| | - Isabel Czarnocki
- Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan
| | - Nancy Si
- Section of Pediatric Surgery, Department of Surgery and the C.S. Mott Children’s Hospital, University of Michigan, Ann Arbor, Michigan
| | - Jonathan Luntz
- Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan
| | - Diann Brei
- Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan
| | - Daniel H. Teitelbaum
- Section of Pediatric Surgery, Department of Surgery and the C.S. Mott Children’s Hospital, University of Michigan, Ann Arbor, Michigan
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Koch KL, Bitar KN, Fortunato JE. Tissue engineering for neuromuscular disorders of the gastrointestinal tract. World J Gastroenterol 2012; 18:6918-25. [PMID: 23322989 PMCID: PMC3531675 DOI: 10.3748/wjg.v18.i47.6918] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2012] [Revised: 11/19/2012] [Accepted: 11/24/2012] [Indexed: 02/06/2023] Open
Abstract
The digestive tract is designed for the optimal processing of food that nourishes all organ systems. The esophagus, stomach, small bowel, and colon are sophisticated neuromuscular tubes with specialized sphincters that transport ingested food-stuffs from one region to another. Peristaltic contractions move ingested solids and liquids from the esophagus into the stomach; the stomach mixes the ingested nutrients into chyme and empties chyme from the stomach into the duodenum. The to-and-fro movement of the small bowel maximizes absorption of fat, protein, and carbohydrates. Peristaltic contractions are necessary for colon function and defecation.
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