Triiodothyronine-Loaded Nanofiber Biomaterial Fabrication for Accelerating Wound Healing

Background and Aim: Skin is the largest organ and plays important rolesin human bodies. Skin can be self-regenerated due to the presence ofstem cells. Notwithstanding the presence of stem cells in the skin, theability of skin to regenerate is limited to deep injuries, which leads tochronic wounds. In recent years, the attempts to find a way to treatchronic non-healing wounds attract a lot of attention. The use ofsynthetic bioactive substrates which deliver growth factors, hormones,and drugs at the site of injuries is an effective way to treat the wounds.Hormones are a class of active molecules that regulate physiological andbehavioral functions of different organs. Triiodothyronine (T3), the activeform of thyroid hormone, stimulates growth in wound healing via thyroidhormone receptor. It was shown that topical delivery of T3 on the site ofinjury in mice promoted wound healing process through the increasein hair follicular keratinocyte protein and improvement in organizing collagen bundles. Due to the toxic effect of intravenous administrationof T3 caused by excess levels in the blood, controlled release ofT3 is recommended. Our aim in this study was to create a bioactivebiocompatible substrate releasing T3 in a sustained manner. In this study,T3-loaded chitosan nanoparticles were added to polycaprolactone(PCL) solution, and electrospinning technique was selected to producenanofiber substrate.Methods: To produce T3-loaded nanoparticles, ionic gelation methodwas employed. 1.7 mg/mL chitosan solution was mixed with 12 mL oftripolyphosphate solution containing T3 as a crosslinker. The mass ratioof chitosan to T3 was 100:1, respectively. Electrospinning technique wasused to produce a nanofiber substrate. PCL solution contained 3%w/v ofT3 loaded-chitosan nanoparticles. The flow rate of the PCL solution wasfixed at 0.5 mL/h. The high voltage applied and the distance betweenneedle and collector were 16 Kv and 15 cm, respectively.Results: The characterization of the size and distribution of T3-loadedchitosan nanoparticles was carried out using dynamic light scattering(DLS) method. The results showed a mean diameter of 91 nm for the T3-loaded chitosan nanoparticles. The loading capacity and encapsulationefficiency of T3 were reported 87% and 8.3 by using ELIZA technique.In addition, the release profile of T3 from nanofiber substrate wasmonitored by using ELIZA technique. The profile showed that the releaseof T3 from substrate lasted for 14 days, and the concentration of T3 wasreached to 133 ng/mL within first 4 days. It continued to increase to165 ng/mL at the end of the 14th day and remained at non-toxic level.SEM micrographs of PCL embedded chitosan nanoparticles were usedto measure fiber diameter. The average size of nanofibers was 738 nm.Conclusion: The dose-dependent effect of drugs, hormones and growthfactors in physiological condition highlights the use of biomaterialsreleasing bioactive molecules in a sustained manner in biomedicalapplication. In this study, composite nanofiber substrate produced bythe electrospinning technique showed a controlled release of T3 inthe therapeutic window which prevents thyrotoxicity caused by highconcentration of T3 in the circulation system.

کلیدواژه ها:

Triiodothyronine ، Polycaprolactone nanofiber ، Chitosan nanoparticle ، Wound healing ، Controlled release