Developmentally-inspired shrink-wrap polymers for mechanical induction of tissue differentiation.
Developmentally-inspired shrink-wrap polymers for mechanical induction of tissue differentiation.
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DOI：
10.1002/adma.201304995
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发表时间：
2014-05-28
影响因子：
29.4
通讯作者：
Ingber, Donald E.
中科院分区：
文献类型：
--
作者：
Hashmi, Basma;Zarzar, Lauren D.;Mammoto, Tadanori;Mammoto, Akiko;Jiang, Amanda;Aizenberg, Joanna;Ingber, Donald E.
Local and abrupt changes in mechanical forces play a fundamental role in control of tissue and organ development. While some investigators have varied material properties of tissue engineering scaffolds to influence cell behavior, no biomaterials have been developed that harness mechanical actuation mechanisms to induce new tissue formation. Here, we describe the development of mechanically-actuatable polymers that induce tissue differentiation by harnessing the physical induction mechanism that drives tooth organ formation in the embryo. The formation of many epithelial organs is triggered when sparsely distributed mesenchymal cells abruptly pack closely together and undergo a “mesenchymal condensation” response. For example, in tooth development, the associated physical compression and rounding of dental mesenchymal cells is sufficient to induce whole organ formation in vitro and in vivo.[1] Inspired by this developmental induction mechanism, we fabricated an artificial, shrink-wrap like polymer scaffold that can stimulate tooth tissue differentiation by abruptly inducing physical compaction of cells cultured within it when warmed to body temperature. A porous, GRGDS-modified, hydrogel scaffold was fabricated from poly (N-isopropylacrylamide)(PNIPAAm), which remains in an expanded form in the cold, and rapidly contracts volumetrically when placed at body temperature. When undifferentiated embryonic dental mesenchymal cells were seeded within this hydrogel sponge and polymer shrinkage was thermally induced by warming, the cells became physically compressed and exhibited a more compact, rounded morphology, as they do when they undergo mesenchymal condensation during tooth organ development in the embryo. This physical change in cell shape stimulated tooth differentiation, as measured by the induction of key odontogenic transcription factors in vitro and stimulation of mineralization in vivo. This polymer-based mechanical actuation mechanism represents a new bioinspired approach to induce organ-specific tissue differentiation that could be useful for stem cell biology, tissue engineering and regenerative medicine.Current design strategies used to fabricate materials for tissue engineering and regenerative medicine focus on the chemistry, structural properties, and three-dimensional (3D) spatial organization of the components that comprise these scaffolds (eg, polymers, ceramics, biomaterials).[2, 3] While current tissue scaffold designs can support cell survival and maintenance of some differentiated cell functions, they do not exhibit the ability to induce major developmental lineage switches that can drive whole organ formation. Thus, we set out to develop materials that mimic the organ inductive properties of certain embryonic tissues. The formation of most organs in the embryo results from complex interactions between adjacent epithelial and mesenchymal tissues.[4–7] An initial instructive signal, provided by one of the tissue layers, is followed by reciprocal exchange of inductive signals, resulting in stepwise differentiation of both tissue components into an integrated organ structure. One of the simplest examples of organ formation is the development of the tooth. In the mouse, the embryonic day (E10) dental epithelium induces a ‘mesenchymal condensation’response in which underlying mesenchymal cells are stimulated to migrate
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影响因子：
6.2
作者：
Takahashi, Hironobu;Matsuzaka, Naoki;Okano, Teruo
通讯作者：
Okano, Teruo
间充质凝结和胚胎齿器官形成的机械化学控制。
影响因子：
11.8
作者：
Mammoto, Tadanori;Mammoto, Akiko;Torisawa, Yu-suke;Tat, Tracy;Gibbs, Ashley;Derda, Ratmir;Mannix, Robert;de Bruijn, Marlieke;Yung, Chong Wing;Huh, Dongeun;Ingber, Donald E.
通讯作者：
Ingber, Donald E.
影响因子：
7.6
作者：
Ohazama, A;Modino, SAC;Sharpe, PT
通讯作者：
Sharpe, PT
影响因子：
3
作者：
MINA, M;KOLLAR, EJ
通讯作者：
KOLLAR, EJ
影响因子：
6.1
作者：
Tekin H;Anaya M;Brigham MD;Nauman C;Langer R;Khademhosseini A
通讯作者：
Khademhosseini A