Silver nanoparticles boost collagen maturation in Achilles tendon regeneration

Track 3: Nanoengineering for Regenerative Medicine and Tissue Enginee... - Session: 3-4 Design and Characterization of Biomaterials: paper no. NEMB2013-93196BACKGROUND: Rupture Achilles tendon remains a problem in modern medicine. Although the content of the healed tendon should approximate the normal tendon after remodeling, the diameters and cross-linking of the collagen fibrils often remain inferior and are susceptible to tendon creep. The mechanical strength of the healed tendon is dictated by the quality of collagen fibrils and their spatial arrangement produced by the tenocytes during the healing process. Silver nanoparticles (AgNPs) has been shown to express antimicrobial effect, accelerate burn wound healing, reduce wound inflammation, modulate collagen deposition and encourage fibroblast differentiation in skin wound healing. Since both skin and tendon healing share similar pathways, it is hypothesized that AgNPs would enhance the healing of injured tendon. The objective of this study is to 1) investigate the in vitro response of tenocytes to AgNPs in the production of collagen; and 2) study the effect of AgNPs in the regeneration of rat Achilles tendon in vivo by assessing the mechanical strength and collagen maturity. MATERIALS AND METHODS: Primary tenocytes were harvested from the Achilles tendon of 4 weeks-old rats and cultured with AgNPs at different concentration. The collagen content was determined using Sirius red/ fast green staining on day 7 and 14. The collagen to non-collagen ratio was then calculated. In vivo rat Achilles tendon injury model was used to investigate the effect of AgNPs to tendon regeneration. Briefly, the Achilles tendon was transected and was either treated with local AgNPs injection every 5 days or left untreated as control. Skin incision was done without transecting the tendon in the sham group. The tendons were harvested at week 6. Tensile test was performed. The collagen fibrils maturity were assessed by Sirius red staining under the polarized microscope. RESULTS: From the results of the Sirius red/ fast green staining, AgNPs significantly increased collagen production at 10uM and 20uM. Tensile test results showed that the modulus of the AgNPs-treated samples significantly outweighed that of the control (p<0.05) and resembled the modulus of the sham. When viewed under polarized microscope using Sirius Red stain, the collagen fibres were found to be more mature in AgNPs-treated group than the control. DISCUSSION AND CONCLUSION: Collagen fibres constitute the tensile strength of tendon. AgNPs enhanced collagen production (in-vitro), encouraged collagen maturation, and improved tensile property in the regenerated tendon. To conclude, AgNPs remarkably enhance the healing of rupture Achilles tendon.link_to_OA_fulltex

The modulating action of silver nanoparticles on collagen deposition in producing scarless wound healing

Session: Skin and Wound Healing: abstract no. 785postprintThe Annual Conference of the North America Chapter of the Tissue Engineering and Regenerative Medicine International Society (TERMIS-NA 2010), Orlando, FL., 5-8 December 2010

Modulation of collagen alignment by silver nanoparticles results in better mechanical properties in wound healing

Our previous study has revealed that silver nanoparticles (AgNPs) have potential to promote wound healing by accelerated re-epithelization and enhanced differentiation of fibroblasts. However, the effect of AgNPs on the functionality of repaired skin is unknown. The aim of this study was to explore the tensile properties of healed skin after treatment with AgNPs. Immunohistochemical staining, quantitative assay and scanning electron microscopy (SEM) were used to detect and compare collagen deposition, and the morphology and distribution of collagen fibers. Our results showed that AgNPs improved tensile properties and led to better fibril alignments in repaired skin, with a close resemblance to normal skin. Based on our findings, we concluded that AgNPs were predominantly responsible for regulating deposition of collagen and their use resulted in excellent alignment in the wound healing process. The exact signaling pathway by which AgNPs affect collagen regeneration is yet to be investigated. © 2011 Elsevier Inc.link_to_subscribed_fulltex

Silver nanoparticles alter proteoglycan expression in the promotion of tendon repair

This study demonstrates a novel method of using silver nanoparticles for Achilles tendon injury healing. In vitro results indicated a stimulatory effect on cell proliferation and collagen synthesis with silver nanoparticles. Biomechanical test on the 42-day post operation Achilles tendon sample exhibited a significant improvement in tensile modulus when compared to the untreated group. Histology suggested that silver nanoparticles promoted cell alignment and proteoglycan synthesis. The collagen deposition was also improved. An alleviation of tumor necrosis factor α, and an increase in fibromodulin and proliferating cell nuclear antigen expression were seen in silver nanoparticles group by immunohistochemistry. This study further corroborates the finding of our previous study that silver nanoparticles help to restore the functionality of injured connective tissues. We believe that the anti-inflammatory nature of silver nanoparticles has an important role in accelerating the healing process and reducing scarring, leading to better functional outcome. From the clinical editor: Tendon healing after surgeries remains a slow and tedious process, typically requiring several weeks of recovery time and gradual introduction of physical therapy. There are no currently utilized methods that could promote tendon healing. In this study, silver nanoparticles are reported to facilitate Achilles tendon repair in a model system, through increased proteoglycan and collagen synthesis, paving the way to potential clinical applications in the future. Copyright © 2014 Elsevier Inc. All rights reserved