Cell migration participates in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. The cells specifically migrate to destiny sites induced by the gradually varying concentration (gradient) of soluble signal factors and the ligands bound with the extracellular matrix in the body during a wound healing process. Therefore, regulation of the cell migration behaviours is of paramount importance in regenerative medicine. One important way is to create a microenvironment that mimics the in vivo cellular and tissue complexity by incorporating physical, chemical and biological signal gradients into engineered biomaterials. In this review, the gradients existing in vivo and their influences on cell migration are briefly described. Recent developments in the fabrication of gradient biomaterials for controlling cellular behaviours, especially the cell migration, are summarized, highlighting the importance of the intrinsic driving mechanism for tissue regeneration and the design principle of complicated and advanced tissue regenerative materials. The potential uses of the gradient biomaterials in regenerative medicine are introduced. The current and future trends in gradient biomaterials and programmed cell migration in terms of the long-term goals of tissue regeneration are prospected.

Eleven structural analogues of two known cationic lipids, N-[1-(2, 3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA) and N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTAP) were synthesized and utilized to evaluate the structural characteristics of DOTMA for its high intravenous transfection activity. Using a CMV-driven expression system and luciferase gene as a reporter, the transfection activity of these analogues was evaluated in mice using tail vein injection. Results concerning the structure-activity relationship with regard to the influence of the backbone, relative position between head group and the hydrophobic chains on the backbone, linkage bonds, as well as the composition of the aliphatic chains revealed that cationic lipids which give a higher in vivo transfection activity share the following structural characteristics: (1) cationic head group and its neighboring aliphatic chain being in a 1,2-relationship on the backbone; (2) ether bond for bridging the aliphatic chains to the backbone; and (3) paired oleyl chains as the hydrophobic anchor. Cationic lipids without these structural features had lower in vivo transfection activity. These structural characteristics, however, did not significantly influence their in vitro transfection activity. The contribution that cationic lipids make to the overall in vivo transfection activity is likely to be determined by the structure of DNA/lipid complexes and by the outcome of the interaction between the DNA/lipid complexes and blood components upon intravenous administration.

Directional migration of cells mediated by gradient cues in vitro can mimic the corresponding biological events in vivo and thereby provides a way to disclose the cascade responses in tissue regeneration processes and to develop novel criteria for design of tissue-inductive biomaterials. In this work, a molecular weight gradient of poly(2-hydroxyethyl methacrylate) (PHEMA) brushes with a thickness ranging from 3 to 30 nm and slopes of 0.8-3.2 nm/mm were fabricated by using surface-initiated atom transfer radical polymerization (ATRP) and a dynamically controlled reaction process. The PHEMA gradients were characterized by X-ray photoelectron spectrometry (XPS) and ellipsometry. The adhesion number, spreading area, adhesion force, and expression of focal adhesion and actin fibers of vascular smooth muscle cells (VSMCs) decreased along with the increase of the PHEMA brushes length. The VSMCs exhibited preferential orientation and enhanced directional migration toward the direction of reduced PHEMA thickness, whose extent was dependent on the gradient slope and polymer thickness. Most of the cells were oriented, and 87% of the cells moved directionally at the optimal conditions.

This review focuses on the recent developments in study of cationic lipids as carriers for DNA delivery. Emphasis is placed on a class of compounds as exemplifies by their similarity in structures and transfection activities. The technical aspects are also reviewed on how to prepare DNA-lipid complexes and to perform transfection. A brief discussion of the current views on the mechanism of cationic lipid-mediated DNA transfer is intended to provide new prospects for future developments and further improvement of the current systems.

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