Sustained-released mixture of vascular endothelial growth factor 165 and fibrin glue strengthens healing of ileal anastomoses in a rabbit model with intraperitoneal infection

Li, Zhanwu; Wang, Wenjun; Wang, Xiaozhou; Jiang, Lei; Wang, Fengyi; Liu, Qiang

doi:10.4174/astr.2017.93.3.159

Cited by 5 publications

(9 citation statements)

References 27 publications

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“…It is also the key reason why we chose the MSCs secretome as a therapeutic agent in our study. We harvested the secretome from the culture medium of MSCs and subsequently detected several growth factors that have been reported to promote surgical anastomotic healing, such as FGF-2, VEGF, and IGF-1 (Oines et al, 2014;Li et al, 2017), which are essential key factors involved in tissue repair and regeneration. In vitro studies also found that the MSCs secretome accelerated the viability of key cells involved in tissue repair in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, studies in the field of intestinal anastomotic healing have employed fibrin glue as the scaffold to deliver exogenous growth factors VEGF (Li et al, 2017), and growth hormone (Li et al, 2007;Wang et al, 2009), demonstrating fibrin glue's application potential as a sustained-release carrier for growth factors. However, compared with MSCs secretome therapy, this kind of mono-factor therapy has significant disadvantages.…”

Section: Discussionmentioning

confidence: 99%

“…However, compared with MSCs secretome therapy, this kind of mono-factor therapy has significant disadvantages. At first, this therapy is not regulated by endogenous negative feedback mechanisms and has the potential to cause tissue hyperproliferation and carcinogenesis (Vajanto et al, 2002;Li et al, 2017;Tamburello et al, 2022). Secondly, this therapy has limited efficacy because tissue repair is accomplished by the concerted action of multiple factors, whereas MSCs secretome therapy has the advantage of containing numerous bioactive factors (Rhatomy et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…The concentrations of FGF-2, VEGF, and IGF-1 were 302.6 pg/mL, 580.01 pg/mL, and 714.05 pg/mL, respectively. Surprisingly, the aforementioned growth factors have also been reported to promote anastomotic repair (Oines et al, 2014;Li et al, 2017).…”

Section: Identification Of Mscs Secretomementioning

confidence: 99%

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Mesenchymal stem cell secretome-loaded fibrin glue improves the healing of intestinal anastomosis

Zhou

Feng

et al. 2023

Front. Bioeng. Biotechnol.

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Anastomotic leakage is a serious complication following gastrointestinal surgery and one of the leading causes of patient mortality. Despite the significant clinical and economic burden, there are currently no reliable treatment options to improve the healing of intestinal anastomosis and subsequently prevent anastomotic leakage. Recently, the development of regenerative medicine has shown promise for improving anastomotic healing. Recent studies have illustrated that stem cell-derived secretome can enhance tissue regeneration without the safety and ethical limitations of stem cell transplantation. Herein, we developed a fibrin glue topical delivery system loaded with mesenchymal stem cells (MSCs)-derived secretome for controlled delivery of bioactive factors, and evaluated its application potential in improving the healing of intestinal anastomosis. Under in vitro conditions, the MSCs secretome significantly promoted cell proliferation viability in a dose-dependent manner and resulted in the controlled release of growth factors via fibrin glue delivery. We established a rat surgical anastomotic model and experimentally found that MSCs secretome-loaded fibrin glue enhanced anastomotic bursting pressure, increased granulation tissue formation and collagen deposition, and significantly promoted anastomotic healing. Mechanistically, fibrin glue accelerated cell proliferation, angiogenesis, and macrophage M2 polarization at the surgical anastomotic site by releasing bioactive factors in the secretome, and it also alleviated the inflammatory response and cell apoptosis at the anastomotic site. Our results demonstrated for the first time that MSCs-derived secretome could promote the healing of intestinal anastomosis. Considering the accessibility and safety of the cell-free secretome, we believed that secretome-loaded fibrin glue would be a cell-free therapy to accelerate the healing of intestinal anastomosis with great potential for clinical translation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Identification Of Mscs Secretomementioning

confidence: 99%

See 2 more Smart Citations

Mesenchymal stem cell secretome-loaded fibrin glue improves the healing of intestinal anastomosis

Zhou

Feng

et al. 2023

Front. Bioeng. Biotechnol.

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“…Thus, the approach of their pharmacological administration could be particularly promising for anastomoses of questionable perfusion. Still, there is very few preclinical, yet positive evidence on administration of EPO and VEGF to improve anastomotic healing [ 11 , 23 , 27 ]. Lack of known side-effects of short time treatment would allow perioperative treatment.…”

Section: Experimental Approaches For Induction Of Anastomotic Healingmentioning

confidence: 99%

Innovative approaches for induction of gastrointestinal anastomotic healing: an update on experimental and clinical aspects

Reischl

Wilhelm

Frieß

2020

Langenbecks Arch Surg

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Purpose In most cases, traditional techniques to perform an anastomosis following gastrointestinal resections lead to successful healing. However, despite focused research in the field, in certain high-risk situations leakage rates remain almost unchanged. Here, additional techniques may help the surgeon to protect the anastomosis and prevent leakage. We give an overview of some of the latest developments on experimental and clinical techniques for induction of anastomotic healing. Methods We performed a review of the current literature on approaches to improve anastomotic healing. Results Many promising approaches with a high clinical potential are in the developmental pipeline. Highly experimental approaches like inhibition of matrix metalloproteinases, stem cell therapy, hyperbaric oxygen therapy, induction of the hypoxic adaptive response, and the administration of growth factors are still in the preclinical phase. Other more clinical developments aim to strengthen the anastomotic suture line mechanically while shielding it from the influence of the microbiome. Among them are gluing, seaming the staple line, attachment of laminar biomaterials, and temporary intraluminal tubes. In addition, individualized bowel preparation, selectively reducing certain detrimental microbial populations could become the next stage of bowel preparation. Compression anastomoses are evolving as an equivalent technique additional to established hand-sewn and stapled anastomoses. Fluorescence angiography and flexible endoscopy could complement intraoperative quality control additionally to the air leak tests. Virtual ileostomy is a concept to prepare the bowel for the easy formation of a stoma in case of leakage. Conclusion A variety of promising diagnostic and prophylactic measures that may support the surgeon in identifying high-risk anastomoses and support them according to their potential deficits is currently in development.

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The comparison of the suture materials on intestinal anastomotic healing: an experimental study

Uzunlu

2023

Ulus Travma Acil Cerrahi Derg

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BACKGROUND: This experimental comparative study was to evaluate the local effects of three different suture materials on intestinal anastomosis healing. METHODS: Ethical approval was obtained from the University of Ethical Committee (E-60758568-020-176720). A prospective, experimental comparative analysis was conducted on 24 rats. They were divided into three equal groups; Group 1 underwent colonic anastomosis with Vicryl suture material, Group 2 underwent colonic anastomosis with polypropylene suture; and Group 3 underwent colonic anastomosis with polydioxanone (PDS) suture. The second operation underwent the 7th post-operative day. Adhesion score, anastomotic leakage, anastomotic bursting pressure, hydroxyproline levels, and histopathologic examination were evaluated. RESULTS: All animals survived, and no leakage, intestinal obstruction, or wound infection was observed during the experiment. The adhesion score was evaluated according to the Diamond classification and same in all groups. Median anastomotic bursting pressure was 125.75 mmHg (10–241) in the Vicryl group, 159.25 mmHg (113–190) in the polypropylene group, and 154.50 mmHg (20–212) in the PDS group. Hydroxyproline tissue concentrations were in the Vicryl group 1699.92±220.8 ng/mg (range: 1509.81–2186.47), in the polypropylene group 1126.24±607.12 ng/mg (range: 53.22–1815.63), and 1547.86±335.2 ng/mg (range: 973.66–1973.2) in PDS group. There was no difference among groups regarding the inflammatory response evaluated by histopathology. There was no statistical significance in all variables evaluated. CONCLUSION: This experimental study demonstrates that suture materials did not worsen tissue healing during intestinal anastomosis. Absorbable, slowly-absorbable, and non-absorbable suture materials could be used safely in every situation.

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Sustained-released mixture of vascular endothelial growth factor 165 and fibrin glue strengthens healing of ileal anastomoses in a rabbit model with intraperitoneal infection

Cited by 5 publications

References 27 publications

Mesenchymal stem cell secretome-loaded fibrin glue improves the healing of intestinal anastomosis

Mesenchymal stem cell secretome-loaded fibrin glue improves the healing of intestinal anastomosis

Innovative approaches for induction of gastrointestinal anastomotic healing: an update on experimental and clinical aspects

The comparison of the suture materials on intestinal anastomotic healing: an experimental study

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