Development of injectable, stimuli-responsive biomaterials as active scaffolds for applications in advanced drug delivery and osteochondral tissue regeneration

Abstract

AcknowledgmentsFirst and foremost, I would like to thank my parents, Dr. John Akintayo Adedoyin and Dr.Omobola Adedoyin for their unconditional love, support and prayers. To my brothers, Dr.Ayodeji Adedoyin, and Mr. Akinola Adedoyin, thank you for your constant encouragement and advice. I owe much appreciation to my current and past lab mates -Meryem, Nandita, Ninad, Wei, Ted, Yang, Yue and Cristian. It has been a pleasure to work alongside you.To all my friends and adopted family at Northeastern, thank you for making my time here enjoyable and filled with wonderful memories. I would like to thank members of the Sridhar lab, specifically Dr. Rajiv Kumar, Codi Gharagouzloo, Bryce Delgado and Muizz Zaman, for their work in helping me with the synthesis and functionalization of the magnetic nanoparticles, developing the mathematical model of the force distribution within the nanocomposite scaffold, and the in vitro sustained drug release studies from the hydrogel that was done in collaboration with their lab. To my advisor, Dr. Adam K.Ekenseair, thank you for your leadership, wisdom and support during the past four and a half years. I also would like to thank my committee members, namely, Dr. Arthur Coury, Dr. Abigail Koppes, and Dr. Srinivas Sridhar for their guidance and mentorship. Lastly, thanks to the Chemical Engineering Community at NEU, without your support, none of this work would be possible. 3 AbstractOsteoarthritis (OA) is a degenerative joint disease that occurs when the cartilage matrix begins to breakdown. Every year, over 3.1 million surgeries are performed in an effort to treat damaged cartilage tissue. 4 Current treatment options such as osteochondral tissue grafting, micro-fracturing, and total knee replacements (TKRs) are effective in alleviating symptoms associated with OA, but often fail to promote the regeneration of normal cartilage. Therefore, due to the limitations of the current treatment options available, it has become necessary to develop better medical solutions to restore or regenerate cartilage tissue previously damaged by OA.Stimuli-responsive hydrogels, capable of exhibiting dramatic changes in swelling behavior, network structure, permeability and mechanical strength in response to changes in their local environment, have emerged as potential candidates as active scaffolds for several tissue engineering applications. Magneto-responsive biomaterials have become a subject of interest in the field of tissue engineering as their physical and structural properties could be manipulated spatiotemporally by varying the magnetic field strength, making them useful for applications in advanced drug delivery and osteochondral tissue regeneration. Thus, the goal of this thesis was to investigate the feasibility of developing an injectable, magneto-responsive hydrogel scaffold capable of delivering viable stem cell populations to a cartilage defect, and to spatiotemporally control the regeneration of the cartilage tissue in vivo.A magneto-responsive biomaterial was made by adding functional pa...

Nanopharmaceuticals and Nanomedicines Currently on the Market: Challenges and Opportunities

“…Triamcinolone acetonide that has been embedded in a PLGA hydrogel, is known as Zilretta R (Flexion Therapeutics, MA, USA), and received its FDA approval in 2017 for treatment of knee osteoarthritis [267][268][269]. This formulation is delivered by intra-articular injection to reduce knee osteoarthritis pain, but its overall positive effects are still under investigation [267,270].…”