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A Novel Bacterial Cellulose Membrane Immobilized With Human Umbilical Cord Mesenchymal Stem Cells-Derived Exosome Prevents Epidural Fibrosis

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A Novel Bacterial Cellulose Membrane Immobilized With Human Umbilical Cord Mesenchymal Stem Cells-Derived Exosome Prevents Epidural Fibrosis

Bo Wang et al. Int J Nanomedicine.

Abstract

Introduction: Failed back surgery syndrome is a situation where there is failure after lumbar surgery aimed at correcting lumbar disease that is characterized by continuous back and/or leg pain. Epidural fibrosis and adhesions are among the major causes of failed back surgery syndrome. In recent years, several biomaterials have been applied as barriers or deterrents to prevent the compression of neural structures by postsurgical fibrosis.

Methods: In this study, a new bacterial cellulose (BC) anti-adhesion membrane, composed of exosomes from human umbilical cord mesenchymal stem cells, was developed. Its structure and morphology, water content, thickness, and mechanical properties of elasticity were analyzed and characterized. The degradation of the BC+exosomes (BC+Exos) membrane in vitro was evaluated, and its in vitro cytotoxicity and in vivo biocompatibility were tested. The prevention effect of BC+Exos membrane on epidural fibrosis post-laminectomy in a rabbit model was investigated.

Results: The BC+Exos membrane showed a three-dimensional network structure constituted of high-purity cellulose and moderate mechanical properties. No degeneration was observed. The BC+Exos membrane showed no cytotoxicity and displayed biocompatibility in vivo. The BC+Exos film was able to inhibit epidural fibrosis and peridural adhesions.

Conclusion: Based on the current findings, the BC+Exos membrane is a promising material to prevent postoperative epidural fibrosis and adhesion.

Keywords: adhesion; bacterial cellulose; epidural fibrosis; exosome; failed back surgery syndrome; human umbilical cord mesenchymal stem cell.

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Identification of human umbilical cord mesenchymal stem cells (HUCMSCs) and HUCMSCs-derived exosomes. Notes: (A) Flow cytometric analysis of the expression of cell surface markers related to HUCMSCs. (B) Bright image of HUCMSCs under a light microscope. (C) Representative image of osteocyte differentiation of HUCMSCs by using cytochemical staining with Alizarin Red. (D) Representative image of adiocyte differentiation of HUCMSCs by using cytochemical staining with Oil Red O. (E) Representative image of chondrocyte differentiation of HUCMSCs by using cytochemical staining with Alcian Blue. (F) Transmission electron microscopic image of HUCMSCs-exosome. (G) The size distribution of the HUCMSCs-exosome was analyzed by using a Zetasizer Nano ZS. (H) The positive markers for exosomes, HSP70, CD63, and CD9 were detected by using Western blotting.
Figure 2
Figure 2
Characterization of the BC membrane and the BC+Exos membrane. Notes: (A and B) The appearance of the BC membrane and the BC+Exos membrane, respectively. (C) The FTIR spectra of the BC membrane and BC+Exos membrane. (D and E) Representative images of the BC membrane and the BC+Exos membrane, respectively. (F) The average diameter of the fibers. Abbreviations: BC, bacterial cellulose; BC+Exos, bacterial cellulose combined with exosomes; FTIR, Fourier transform infrared spectrometer.
Figure 3
Figure 3
The properties of the BC membrane and the BC+Exos membrane. Notes: (A) Water content. (B and C) Tensile strength of the BC membrane and the BC+Exos membrane, respectively. (D) Elongation at break. (E) Elastic modulus. (F) Degradation during 6 months. Abbreviations: BC, bacterial cellulose; BC+Exos, bacterial cellulose combined with exosomes.
Figure 4
Figure 4
Biocompatibility of the BC+Exos membrane in vitro. Notes: Representative images of live/dead cell staining at Day 1 (AC), Day 3 (DF), and Day 5 (GI) in the culture plate, BC membrane group, and BC+Exos membrane group. The percentage of living cells (J) and CCK-8 values (K) in each group. All data were expressed as means ± standard error of mean. Abbreviations: BC, bacterial cellulose; BC+Exos, bacterial cellulose combined with exosomes.
Figure 5
Figure 5
Biocompatibility of the BC+Exos membrane in vivo. Notes: (A and B) Representative images of the area surrounding both the BC+Exos membrane and muscle at 1 week postoperatively. (C and D) Representative images of the area surrounding both the BC+Exos membrane and subcutaneous tissue at 1 week postoperatively. Blood tests of ALT (E), AST (F), BUN (G), and Scr (H) were conducted at days 1, 3, 7, 30, and 90 after surgery, respectively. Representative images of the long-term effect of the BC+Exos membrane on the heart (I), liver (J), and kidney (K). Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BC, bacterial cellulose; BC+Exos, bacterial cellulose combined with exosomes; BUN, blood urea nitrogen; Scr, serum creatinine.
Figure 6
Figure 6
General view and MRI examination. Notes: (AE) At 1 year postoperatively, the general observation of the control, ePTFE membrane, PU membrane, BC membrane, and BC+Exos membrane groups, respectively. (FJ) At 1 year postoperatively, the T1-weighted MRI images of the control, ePTFE membrane, PU membrane, BC membrane, and BC+Exos membrane groups, respectively. (KO) At 1 year postoperatively, the T2-weighted MRI images of the control, ePTFE membrane, PU membrane, BC membrane, and BC+Exos membrane groups, respectively. Abbreviations: BC, bacterial cellulose; BC+Exos, bacterial cellulose combined with exosomes; ePTFE, expanded polytetrafluoroethylene; MRI, magnetic resonance image; PU, polyurethane.
Figure 7
Figure 7
Histological examination. Notes: (A, a, B, b, C, c, D, d, E, and e) The HE staining images of the control, ePTFE membrane, PU membrane, BC membrane, and BC+Exos membrane groups at 1 year post operation, respectively. (F, f, G, g, H, h, I, i, J, and j) The Masson trichrome images of the control, ePTFE membrane, PU membrane, BC membrane, and BC+Exos membrane groups at 1 year post operation, respectively. (KO) The Sirius red staining of the control, ePTFE membrane, PU membrane, BC membrane, and BC+Exos membrane groups at 1 year post operation, respectively. Abbreviations: BC, bacterial cellulose; BC+Exos, bacterial cellulose combined with exosomes; ePTFE, expanded polytetrafluoroethylene; MRI, magnetic resonance image; PU, polyurethane.
Figure 8
Figure 8
The mRNA levels of fibrosis-related genes. Notes: The mRNA levels of (A) COL I, (B) COL III, and (C) α-SMA were determined for the healthy, control, ePTFE membrane, PU membrane, BC membrane, and BC+Exos membrane groups at 4, 8, and 12 months post operation. Each assay was repeated three times. All data are expressed as means ± standard error of mean. *P<0.05, **P<0.01. Abbreviations: α-SMA, alpha smooth muscle actin; BC, bacterial cellulose; BC+Exos, bacterial cellulose combined with exosomes; COL I, collagen type I; COL III, collagen type III; ePTFE, expanded polytetrafluoroethylene; mRNA, messenger ribonucleic acid; ns, not significant; PU, polyurethane.

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References

    1. Thomson S. Failed back surgery syndrome – definition, epidemiology and demographics. Br J Pain. 2013;7(1):56–59. - PMC - PubMed
    1. Skaf G, Bouclaous C, Alaraj A, Chamoun R. Clinical outcome of surgical treatment of failed back surgery syndrome. Surg Neurol. 2005;64(6):483–488. - PubMed
    1. Ido K, Urushidani H. Fibrous adhesive entrapment of lumbosacral nerve roots as a cause of sciatica. Spinal Cord. 2001;39(5):269–273. - PubMed
    1. Richter HP, Kast E, Tomczak R, Besenfelder W, Gaus W. Results of applying ADCON-L gel after lumbar discectomy: the German ADCON-L study. J Neurosurg. 2001;95(2 Suppl):179–189. - PubMed
    1. Liu LS, Berg RA. Adhesion barriers of carboxymethylcellulose and polyethylene oxide composite gels. J Biomed Mater Res. 2002;63(3):326–332. - PubMed

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