Related Experiment Video
Updated: Mar 9, 2026
Design of a Biocompatible Drug-Eluting Tracheal Stent in Mice with Laryngotracheal Stenosis
Published on: January 21, 2020
Tacrolimus-Eluting Suture Inhibits Neointimal Hyperplasia: An Experimental In Vivo Study in Rats
K Ak1, E Ak2, O Dericioglu3
1Marmara University Faculty of Medicine, Department of Cardiovascular Surgery, Marmara Universitesi Pendik Egitim ve Arastırma Hastanesi, Ustkaynarca Pendik, Istanbul, Turkey; Eastern Mediterranean University, Faculty of Medicine, Gazimagusa, Cyprus.
Objective/Background:
Neointimal hyperplasia (NIH) remains one of the leading causes of graft failure after vascular anastomoses. Cytotoxic drugs, such as rapamycin and tacrolimus, have been shown to inhibit the development of NIH. In this study, the aim was to test the impact of a sustained releasing tacrolimus-chitosan-eluting suture on the development of NIH in a rat model.
Methods:
After tacrolimus-chitosan coating of a 7/0 polyvinylidene difluoride (PVDF) Trofilen® suture, the tacrolimus concentration on the coated suture and in vitro release trials were performed spectrophotometrically. Twelve Wistar rats were included. After midline laparotomy, a 7-8 mm longitudinal aortotomy in the infrarenal aorta was made and then closed by a bare 7/0 PVDF (group C, n = 6) and a 7/0 tacrolimus-chitosan coated PVDF suture (0.65 μg/cm tacrolimus [0.9 wt%] + 1.82 μg/cm chitosan [2.28 wt%]) (group T, n = 6). After 1 month, rats were sacrificed and aortotomy sites were examined histologically by ratio of intimal area (including neointima) and immunohistochemically by α-smooth muscle actin (ASMA) and proliferating cell nuclear antigen (PCNA) immunostaining. The PCNA positive cells were indexed to total cell number and expressed as percentage.
Results:
In vitro tacrolimus release tests for a 7/0 tacrolimus-chitosan coated PVDF suture were confirmed for 1 month without an initial burst release. Endothelialisation over the aortotomy line occurred in both groups. The area of neointima was significantly reduced in group T compared with group C (ratio 0.22 ± 0.12 vs. 0.42 ± 0.11; p = .017) 1 month post-operatively. Likewise, the percentage of PCNA immunostaining significantly decreased in group C compared with group T (3.83 ± 2.85% vs. 11.17 ± 7.78%; p = .026). The cells constituting NIH were positive for ASMA immunostaining.
Conclusions:
Tacrolimus-chitosan-eluting suture is shown to be an effective way to reduce NIH without interfering with normal endothelialisation.
Insights
A novel tacrolimus-chitosan-eluting suture effectively reduced neointimal hyperplasia (NIH) in a rat model. This innovative vascular graft material shows promise for preventing graft failure without hindering endothelialization.
Area of Science:
- Biomaterials Science
- Vascular Surgery
- Drug Delivery Systems
Background:
- Neointimal hyperplasia (NIH) is a primary cause of vascular graft failure.
- Cytotoxic drugs like rapamycin and tacrolimus can inhibit NIH.
- Sustained drug release from sutures offers a potential therapeutic strategy.
Purpose of the Study:
- To evaluate the efficacy of a sustained-release tacrolimus-chitosan-eluting suture in preventing NIH.
- To assess the impact of this novel suture on graft healing in a rat model.
Main Methods:
- Polyvinylidene difluoride (PVDF) sutures were coated with tacrolimus and chitosan.
- In vitro drug release studies confirmed sustained tacrolimus elution for one month.
- Aortotomies in Wistar rats were closed with either bare or coated sutures.
- Histological and immunohistochemical analyses (ASMA, PCNA) were performed after one month.
Main Results:
- The tacrolimus-chitosan suture demonstrated sustained drug release without an initial burst.
- Significantly reduced neointimal area was observed in the tacrolimus-eluting suture group compared to controls (p=0.017).
- A significant decrease in proliferating cell nuclear antigen (PCNA) positive cells was noted in the treated group (p=0.026).
- Alpha-smooth muscle actin (ASMA) staining confirmed smooth muscle cell differentiation in the neointima.
Conclusions:
- Tacrolimus-chitosan-eluting sutures effectively reduce neointimal hyperplasia.
- This approach shows potential for improving vascular graft patency.
- The elution strategy does not impede normal endothelialization of the anastomosis.
