Hyaluronan Hydrogel Platform for Musculoskeletal Regeneration

سال انتشار: 1397
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 360

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شناسه ملی سند علمی:

NSCMRMED03_006

تاریخ نمایه سازی: 30 دی 1397

چکیده مقاله:

Background and Aim: Hyaluronic acid (HA) is one of the mainextracellular matrix components that is involved in various biologicalevents, including tissue development and regeneration, cell motilityand viscoelasticity. HA has been used commonly for the formulationof drug delivery systems and regenerative medicine constructs. Havingcapitalized on an unconventional conjugation method, in this currentstudy, we report on a series of derivatives providing HA with tunablepseudoplasticity, temperature-induced gelation and dual enzymatic/light-induced gelation.Methods: In this study, HA was conjugated via DMTMM-mediatedamidation with (i) an array of substrates including small, large andfunctional molecules for validating the method, (ii) short alkyl chainsof propyl and butylamine, (iii) thermoresponsive moieties, (iv) tyramine.The formulated products were characterized by means of rheometer,1H-NMR and UV-vis spectrophotometry. The reaction kinetics andcoupling yields were assessed under a spectrum of conditions. To deliverchemokines in vivo in a rabbit osteochondral defect model, we used thethermoresponsive derivative. Further, the HA-tyramine derivative wasoptimized for the additive manufacturing with a dual enzymatic andlight gelation.Results: In this study, we used the thermoresponsive derivative for in situtissue engineering. After one week, an increased cell density was foundwithin the rabbit osteochondral defect upon the delivery of chemokinescompared to chemokine-free gel. The current method seems to be anattractive strategy since it can facilitate the endogenous cell recruitment,eliminating the need for tissue harvesting and cell expansion. Besides,the application of HA-tyramine for 3D printing showed that (i) thedual gelation allowed good extrusion properties and reliable shapemaintenance; (ii) cells can attach and spread within the material also inthe absence of cell-binding peptides; (iii) a low concentration of polymer(2.5%) and low degree of substitutions (6.0% to 14.5%) can be used toobtain gelation. Furthermore, this method is free from the use of UV light and has no safety concerns regarding the UV-induced DNA damage andtumorigenesis.Conclusion: We have demonstrated how chemical modification canimprove the technological properties of HA including viscoelastic profile,drug delivery and 3D printing capability. These derivatives are valuabletools for fabricating constructs in tissue engineering and regenerative medicine.

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نویسندگان

Mauro Alini

AO Research Institute, Davos Platz, Switzerland