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Cheong, Hogyun,Kim, Jimin,Kim, Bum Jin,Kim, Eunjin,Park, Hae Yeon,Choi, Bong-Hyuk,Joo, Kye Il,Cho, Mi-La,Rhie, Jong Won,Lee, Jong In,Cha, Hyung Joon Elsevier 2019 Acta Biomaterialia: structure-property-function re Vol.90 No.-
<P><B>Abstract</B></P> <P>Limited regenerative capacity of the nervous system makes treating traumatic nerve injuries with conventional polymer-based nerve grafting a challenging task. Consequently, utilizing natural polymers and biomimetic topologies became obvious strategies for nerve conduit designs. As a bioinspired natural polymer from a marine organism, mussel adhesive proteins (MAPs) fused with biofunctional peptides from extracellular matrix (ECM) were engineered for accelerated nerve regeneration by enhancing cell adhesion, proliferation, neural differentiation, and neurite formation. To physically promote contact guidance of neural and Schwann cells and to achieve guided nerve regeneration, MAP was fabricated into an electrospun aligned nanofiber conduit by introducing synthetic polymer poly(lactic-co-glycolic acid) (PLGA) to control solubility and mechanical property. <I>In vitro</I> and <I>in vivo</I> experiments demonstrated that the multi-dimensional tactics of combining adhesiveness from MAP, integrin-mediated interaction from ECM peptides (in particular, IKVAV derived from laminin α1 chain), and contact guidance from aligned nanofibers synergistically accelerated functional nerve regeneration. Thus, MAP-based multi-dimensional approach provides new opportunities for neural regenerative applications including nerve grafting.</P> <P><B>Statement of significance</B></P> <P>Findings in neural regeneration indicate that a bioinspired polymer-based nerve conduit design should harmoniously constitute various factors, such as biocompatibility, neurotrophic molecule, biodegradability, and contact guidance. Here, we engineered three fusion proteins of mussel-derived adhesive protein with ECM-derived biofunctional peptides to simultaneously provide biocompatibility and integrin-based interactions. In addition, a fabrication of robust aligned nanofiber conduits containing the fusion proteins realized suitable biodegradability and contact guidance. Thus, our multi-dimensional strategy on conduit design provided outstanding biocompatibility, biodegradability, integrin-interaction, and contact guidance to achieve an accelerated functional nerve regeneration. We believe that our bioengineered mussel adhesive protein-based multi-dimensional strategy would offer new insights into the design of nerve tissue engineering biomaterials.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Choi, Bong-Hyuk,Cheong, Hogyun,Ahn, Jin-Soo,Zhou, Cong,Kwon, Jong Jin,Cha, Hyung Joon,Jun, Sang Ho The Royal Society of Chemistry 2015 Journal of Materials Chemistry B Vol.3 No.4
<P>Xenograft bone substitutes, such as deproteinized bovine bone mineral (DBBM), have been widely employed as osteoconductive structural materials for bone tissue engineering. However, the loss of xenograft bone substitute particles in defects has been a major limitation, along with a lack of osteoinductive function. Mussel adhesive protein (MAP), a remarkable and powerful adhesive biomaterial in nature, can attach to various substrates, even in wet environments. Its adhesive and water-resistant abilities are considered to be mainly derived from the reduced catechol form, 3,4-dihydroxyphenylalanine (DOPA), of its tyrosine residues. Here, we evaluated the use of DOPA-containing MAP as a functional binder biomaterial to effectively retain DBBM particles at the defect site during<I>in vivo</I>bone regeneration. We observed that DOPA-containing MAP was able to bind DBBM particles easily to make an aggregate, and grafted DBBM particles were not lost in a defect in the rat calvaria during the healing period. Importantly, grafting of a DOPA-containing MAP-bound DBBM aggregate resulted in remarkably accelerated<I>in vivo</I>bone regeneration and even bone remodeling. Interestingly, we found that the DOPA residues in the modified MAP had an osteoinductive ability based on clear observation of the<I>in vivo</I>maturation of new bones with a similar bone density to the normal bone and of the<I>in vitro</I>osteogenic differentiation of osteoblast cells. Collectively, DOPA-containing MAP is a promising functional binder biomaterial for xenograft bone substitute-assisted bone regeneration with enhanced osteoconductivity and acquired osteoinductivity. This mussel glue could also be successfully utilized as a potential biomaterial for general bone tissue engineering.</P>