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Synthesis and in Vitro/in Vivo Evaluation of Bioprinted and Core-Shell Systems Containing Proteoglycan Nanoparticle and Growth Factor for Skin Tissue Regeneration

Zandi, Nooshin | 2020

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  1. Type of Document: Ph.D. Dissertation
  2. Language: Farsi
  3. Document No: 52768 (48)
  4. University: Sharif University of Technology
  5. Department: Institute for Nanoscience and Nanotechnology
  6. Advisor(s): Simchi, Abdolreza; Shokrgozar, Mohammad Ali; Tamjid, Elnaz
  7. Abstract:
  8. Tissue engineering has the potential to revolutionize our health care system. Conceptually, lost or malfunctioning tissues will be replaced by man-made biological substitutes to restore, maintain, or improve function. Tissue engineering has already shown great promise to contribute to treatments of a myriad of diseases including osteoarthritis, cancer, diabetes, skin burns, cardiovascular conditions and various traumatic injuries. Tissue engineering is a highly multidisciplinary discipline that demands integration of knowledge, tools and skills from biology, chemistry, engineering and medicine. Integrating nano- and microtechnologies into clinically sized implants represents a major opportunity to gain control over cellular microenvironments. Here we aim to investidation of the nano-technology that has been explored to realize the next generation of tissue engineered implants. The objective of this PhD is focus on the preparation of nanoengineered bioactive scaffolds using natural and synthetic biopolymer for tissue regeneration. two different method were used to engineer the scaffold including electrospinning, 3D bioprinting and photocurable hydrogel. The first part of the present study was effort to achieve much accelerated wound healing effects through designing of a biomimetic bilayer scaffold containing of gelatin nanofiber to fabricate Extracellular Matrix fibrous (as dermis) and photocrosslinkable Gelatin metacryloyl (GelMA)/silicate nanoparticle-loaded epidermal growth factor nanocomposite hydrogel named as epidermis for full-thickness wound healing application. result shows that silicate nanoplatelet not only enables to increase the mechanical strength of hydrogel but also the small amount of this nanostructure (1%wt) significantly enhanced adhesion to native tissue (3.5 fold) through in vitro wound closure analysis. In the established excisional full-thickness wound model, Bilayer scaffold treatment significantly enhanced wound closure (93.1%±1.54%) after 14 days through increasing granulation tis¬sue formation, collagen deposition, and angiogenesis, relative to individual single layer and normal saline treated groups. the next study of work was we present novel shear thinning and printable hydrogels based on disk-shape silicate nanomaterials, Laponite (LA), combined with glycosaminoglycan nanoparticles (GAGNPs) for extrusion-based bioprinting applications. Engineered nanocomposite hydrogels (GLgels) were rapidly formed within a few seconds due to the interaction between the negatively charged groups of GAGNPs and the edges of LA. In native tissues, the sulfated residual of glycosaminoglycan (GAG) polymer chains of proteoglycans immobilizes growth factors through the proteoglycans/proteins’ complexation with nanoscale organization. These biological assemblies can influence growth factor-cell surface receptor interactions, cell differentiation, cell-cell signaling, as well as the mechanical properties of the tissues. Here, we introduce a facile procedure to prepare novel biomimetic proteoglycan nanocarriers, based on naturally-derived polymers, for the immobilization and controlled release of growth factors. We developed polyelectrolyte complex nanoparticles (PCNs) as growth factor nanocarriers, which mimic the dimension, chemical composition, and growth factor immobilization of proteoglycans in the native tissue. PCNs were prepared by polymer-polymer pair reaction method and characterized for physicochemical properties. The shear thinning behavior of the resulting hydrogels protected encapsulated cells from aggressive shear stresses during bioprinting. The developed bioinks could be easily printed into shape-persistent and free-standing structures with higher aspect ratios. Rheological studies demonstrated fast recoverability of GLgels over multiple strain cycles as determined by step-strain recovery time analysis. In vitro studies confirmed the ability of GLgels to support cell growth, proliferation, and spreading over 5 days of culture. In vitro osteogenic differentiation of pre-osteoblasts murine bone marrow stromal cells encapsulated inside the GLgels was also shown through evaluation of ALP activity and calcium deposition. The engineered shear thinning hydrogel with osteoinductive characteristics can be used as a new bioink for 3D printing of constructs for bone tissue engineering applications
  9. Keywords:
  10. Tissue Engineering ; Skin Regeneration ; Hydrogel ; Electrospinning ; Bioactive Scaffold ; Electrospun Nanofibers ; Hydrogel Nanocomposite ; Three Dimentional Printing

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