Intervention using a novel biodegradable hollow stent containing polylactic acid-polyprolactone-polyethylene glycol complexes against lacrimal duct obstruction disease

Abstract

Lacrimal duct obstruction disease (LDOD) is a common ophthalmologic disease. Stent implantation surgery is one of the most effective therapies. In this study, we intended to find out the satisfactory biodegradable stents containing poly-L-lactic acid-polycaprolactone-polyethylene glycol (PLLA- PCL- PEG) complexes for therapeutic application in LDOD. Stents made of PLLA- PCL- PEG complexes in various ratios, were prepared and used in vitro to determine stents with appropriate mechanical properties and shorter range of bio-degradation for study in vivo. Thirty-two rabbits were randomized into eight groups of four eyes each in advance for test in vivo. The selected stents were implanted into the left lacrimal ducts of 16 rabbits and silica gel stents as the control for the other 16 rabbits. At four points in time (1, 4, 10 and 16 weeks after the implantation), weight loss rate (WLR) of the stents was measured and analysed. To access the change of lacrimal duct, fluorescein excretion test, lacrimal duct endoscopy and histopathological testing were conducted. The stent containing PLLA: PCL6: 4+ 15%PEG was selected for study in vivo. Analysis of weight loss rate (WLR), fluorescein excretion test, lacrimal duct endoscopy and histopathological testing indicated that the selected stent was biodegradable and caused minimal stimulation and earlier tissue restoration in the lacrimal epithelium compared with the silica gel stent used as the control. The study results suggest that the PLLA: PCL6: 4+ 15% PEG stent is a satisfactory biodegradable stent as a promising alternative for therapeutic application in LDOD, which showed tissue compatibility, biodegradation and adequate mechanical intensity.

Fig 1

Chemical structure of PLLA (a); PCL (b); PEG (c).

Fig 2

Four representative stents designed for lacrimal duct implantation are shown in Image A. The pure PLLA stent, PLLA; PCL6:4 stent; PLLA: PCL6:4 + 15% PEG; and silica gel stent correspond to the numbers below: 1, 2, 3 and 4. All of them showed smooth surface and hollow configuration. Image B shows the location and mechanism of lacrimal stent fixation at the lacrimal duct after implantation.

Fig 3

Diagram A shows the impact strength of PLLA- PCL- PEG blends at different ratios while Diagram B shows T_g of the blends. Twenty samples of each blend at different ratios were selected randomly for the test. In Diagram A, PCL increased the impact strength of the blends while PEG neutralized the effect. In Diagram B, T_g of the blends was decrease by PEG though having nothing to do with the proportion of PEG. The standard deviation is represented by the error bars (P < 0.05). * indicates a statistically significant difference.

Fig 4. Snapshots of the lacrimal duct endoscopy at four different time points.

A1-4 and B1-4 denote the typical endoscopy condition of Group A_1-4 and B_1-4. Normal mucosa of the lacrimal duct is rosy and smooth. Hemorrhage (A1) and edema (B1) were common at Week 1 because of acute stimulation by the stents. With time, the mucosa turned red and white, suggesting fibrosis due to inflammation. Papillary epithelial hyperplasia was observed in B3. At Week 16, the mucosa of Group A turned red (A4) while the fibrosis was worse in Group B and the mucosa became pale and rough (B4).

Fig 5

HE staining of Groups A and B at four different time points. Similarly, A1-4 and B1-4 represent the typical histopathology of Groups A_1-4 and B_1-4. Lumen was located on the upper side of the images. The epithelium, sub-epithelial tissue and muscular layer were located downwards (magnification of A8 was 100× while the other groups were 200×).