TY - GEN
T1 - Hierarchical Hydrogel Drug Delivery System Enables Controlled Release of Adeno-Associated Viruses for Gene Therapy
AU - Miyahara, Hideo
AU - Kurashina, Yuta
AU - Ogawa, Yuki
AU - Kurihara, Ayumu
AU - Yoshida, Tomohiko
AU - Okano, Hirotaka James
AU - Fujioka, Masato
AU - Onoe, Hiroaki
N1 - Funding Information:
This work was partly supported by The Translational Research Program; strategic promotion for practical application of innovative medical technology, Japan Agency for Medical Research and Development (AMED).
Publisher Copyright:
© 2019 IEEE.
PY - 2019/1
Y1 - 2019/1
N2 - This paper describes a drug delivery system (DDS) to release Adeno-associated viruses (AAVs) for gene therapy. Our system has two-level hierarchical structures made of different hydrogel materials: (i) Calcium alginate hydrogel microparticles (\sim 100\ \mu \mathrm{m} in diameter) that can properly immobilize AAVs inside and release them for gene transfection triggered by enzymatic degradation, and (ii) a millimeter-scale collagen sheet that encapsulates those alginate microparticles with AAVs for stable fixation to even a tiny and complicated diseased site in our body, such as an inner ear for the treatment of hereditary hearing loss (Figure 1). We fabricated the AAVs-immobilized hydrogel microparticles and evaluated their AAV releasing functions by measured the gene transfection ratio to cultured HeLa cells. In addition, we also demonstrated that the controlled release of AAVs immobilized in the alginate microparticles embedded in the millimeter-scale collagen sheet can be externally triggered from the outside. We envision that our developed composite hydrogel DDS could be an essential and general tool for gene therapy in practical medical scenes, especially in the treatment at complicated internal sites.
AB - This paper describes a drug delivery system (DDS) to release Adeno-associated viruses (AAVs) for gene therapy. Our system has two-level hierarchical structures made of different hydrogel materials: (i) Calcium alginate hydrogel microparticles (\sim 100\ \mu \mathrm{m} in diameter) that can properly immobilize AAVs inside and release them for gene transfection triggered by enzymatic degradation, and (ii) a millimeter-scale collagen sheet that encapsulates those alginate microparticles with AAVs for stable fixation to even a tiny and complicated diseased site in our body, such as an inner ear for the treatment of hereditary hearing loss (Figure 1). We fabricated the AAVs-immobilized hydrogel microparticles and evaluated their AAV releasing functions by measured the gene transfection ratio to cultured HeLa cells. In addition, we also demonstrated that the controlled release of AAVs immobilized in the alginate microparticles embedded in the millimeter-scale collagen sheet can be externally triggered from the outside. We envision that our developed composite hydrogel DDS could be an essential and general tool for gene therapy in practical medical scenes, especially in the treatment at complicated internal sites.
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U2 - 10.1109/MEMSYS.2019.8870781
DO - 10.1109/MEMSYS.2019.8870781
M3 - Conference contribution
AN - SCOPUS:85074340147
T3 - Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems (MEMS)
SP - 601
EP - 602
BT - 2019 IEEE 32nd International Conference on Micro Electro Mechanical Systems, MEMS 2019
PB - Institute of Electrical and Electronics Engineers Inc.
T2 - 32nd IEEE International Conference on Micro Electro Mechanical Systems, MEMS 2019
Y2 - 27 January 2019 through 31 January 2019
ER -