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Developing Polymeric Carriers for Delivery of Platelet Lysate Aiming Tissue Regeneration

Jooybar, Elaheh | 2018

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  1. Type of Document: Ph.D. Dissertation
  2. Language: Farsi
  3. Document No: 51551 (06)
  4. University: Sharif University of Technology
  5. Department: Chemical and Petroleum Engineering
  6. Advisor(s): Abdekhodaie, Mohammad Jafar; Mousavi, Abbas
  7. Abstract:
  8. The goal of tissue engineering is the restoration of a tissue function based on combination of cells, scaffolds, and biological signals in an engineered structure. The best way to develop this issue is mimicking the body and host tissues. In the present thesis, it was tried to improve cartilage tissue regeneration from two aspects. In the first part, an injectable hydrogel based on hyaluronic acid (HA) biomaterial was developed which was incorporated with platelet lysate (PL), as an autologous source of growth factors. The human mesenchymal stem cells (hMSCs) were encapsulated in the hydrogel and the effects of PL on the cell attachment, viability and differentiation toward chondrocytes were investigated. The hydrogels were prepared by enzymatic crosslinking method. First, tyramine was conjugated to the HA backbone, and then the network was prepared in the presence of horseradish peroxidase (HRP) enzyme and low concentrations of hydrogen peroxide. In contrast to a retained round shape of the cells when using pure HA hydrogel, the hMSCs attached and spread out in PL enriched matrix. The enrichment of hMSCs laden HA hydrogels with PL induced a cartilage like extra cellular matrix deposition in vitro. The hMSCs increasingly deposited collagen type II and proteoglycans over time. In the second part, hyaluronic acid based microgels were synthesized for delivery of proteins present in the PL. The high water content of the polymeric network and the inherent negative charge of the HA microgels provided a suitable platform for encapsulation of cationic proteins. As the growth factors present in PL have a positive charge, the developed microgels were a good candidate for PL delivery. The microgels presented a sustained release of PL growth factors for a period of two weeks. The proliferation of hMSCs was enhanced in the presence of PL-loaded microgels. The PL enriched microgels may be injected in the desired site or embedded in the structure of other scaffolds to enhance the bioactivity of the structures by providing a source of growth factors. In general, this thesis introduces injectable hydrogel and microgels based on HA which can be incorporated with platelet lysate to be used in the clinical applications
  9. Keywords:
  10. Injectable Hydrogel ; Enzymatic Crosslinking ; Microgel ; Platelet Lysate ; Hyaluronic Acid Gel ; Tissue Engineering