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Jiang L.Y.,Peking University | Liu J.Y.,Peking University | Wang K.,Peking University | Gu X.,Peking University | And 2 more authors.
Science China Life Sciences | Year: 2014

Immunoisolation is an important strategy to protect transplanted cells from rejection by the host immune system. Recently, microfabrication techniques have been used to create hydrogel membranes to encapsulate microtissue in an arrayed organization. The method illustrates a new macroencapsulation paradigm that may allow transplantation of a large number of cells with microscale spatial control, while maintaining an encapsulation device that is easily maneuverable and remaining integrated following transplantation. This study aims to investigate the design principles that relate to the translational application of micropatterned encapsulation membranes, namely, the control over the transplantation density/quantity of arrayed microtissues and the fidelity of pre-formed microtissues to micropatterns. Agarose hydrogel membranes with microwell patterns were used as a model encapsulation system to exemplify these principles. Our results show that high-density micropatterns can be generated in hydrogel membranes, which can potentially maximize the percentage volume of cellular content and thereby the transplantation efficiency of the encapsulation device. Direct seeding of microtissues demonstrates that microwell structures can efficiently position and organize pre-formed microtissues, suggesting the capability of micropatterned devices for manipulation of cellular transplants at multicellular or tissue levels. Detailed theoretical analysis was performed to provide insights into the relationship between micropatterns and the transplantation capacity of membrane-based encapsulation. Our study lays the ground for developing new macroencapsulation systems with microscale cellular/tissue patterns for regenerative transplantation. © 2014 The Author(s).

Jiang L.-Y.,Peking University | Luo Y.,Peking University | Luo Y.,National Engineering Laboratory for Regenerative and Implantable Medical Devices
Soft Matter | Year: 2013

Engineering microvessel structures with spatial control has important implications for tissue engineering and regenerative medicine. We demonstrate a facile approach to integrate structural and biochemical patterns on biodegradable hydrogel matrices via combining soft-lithographic and micromolding techniques to enable self-assembly of endothelial cells toward vessel morphogenesis. Human umbilical cord vein endothelial cells (HUVECs), with or without stromal fibroblasts, were cultured on matrices made of hyaluronic acid-dextran or agarose hydrogels patterned with microgrooves containing entrapped collagen. It was found that only with appropriate microgroove geometry would the patterned matrices induce the aggregation and coalescence of endothelial cells to form microvessel-like structures. On the basis of the monoculture model, a co-culture configuration mimicking the natural vessel morphology was also established on the hyaluronic acid-dextran matrix, which contained double layered cellular assemblies through recruitment of fibroblasts to the surface of the pre-assembled endothelial cords. This study shows that the hydrogel matrices patterned with microgrooves provide a new and versatile system to enable the morphogenetic assembling of cells and warrant further studies for engineering microvessel tissues. This journal is © 2013 The Royal Society of Chemistry.

Wang K.,Peking University | Luo Y.,Peking University | Luo Y.,National Engineering Laboratory for Regenerative and Implantable Medical Devices
Biomacromolecules | Year: 2013

As one important category of biological molecules on the cell surface and in the extracellular matrix (ECM), glycosaminoglycans (GAGs) have been widely studied for biomedical applications. With the understanding that the biological functions of GAGs are driven by the complex dynamics of physiological and pathological processes, methodologies are desired to allow the elucidation of cell-GAG interactions with molecular level precision. In this study, a microtiter plate-based system was devised through a new surface modification strategy involving polydopamine (PDA) and GAG molecules functionalized with hydrazide chemical groups. A small library of GAGs including hyaluronic acid (with different molecular weights), heparin, and chondroitin sulfate was successfully immobilized via defined binding sites onto the microtiter plate surface under facile aqueous conditions. The methodology then allowed parallel studies of the GAG-modified surfaces in a high-throughput format. The results show that immobilized GAGs possess distinct properties to mediate protein adsorption, cell adhesion, and inflammatory responses, with each property showing dependence on the type and molecular weight of specific GAG molecules. The PDA-assisted immobilization of hydrazide-functionalized GAGs allows biomimetic attachment of GAG molecules and retains their bioactivity, providing a new methodology to systematically probe fundamental cell-GAG interactions to modulate the bioactivity and biocompatibility of biomaterials. © 2013 American Chemical Society.

Gray W.D.,Peking University | Gray W.D.,Georgia Institute of Technology | Wu R.J.,Peking University | Yin X.,Peking University | And 7 more authors.
Biomacromolecules | Year: 2013

Dendrimers feature a defined number of terminal groups that may bind RNA or be functionalized with bioactive molecules. These competing uses of terminal groups may create an impasse if the requisite density of ligands depletes the number of terminal groups for binding sufficient RNA, or vice versa. A novel dendrimeric platform is needed that maintains high ligand density while retaining sufficient microRNA-binding terminal groups. Here we present a dendrimeric "bowtie" consisting of one-half devoted to microRNA binding and the other half to ligand presentation. We demonstrate its suitability as a transfection agent by delivering miR-126 to human vascular endothial cells (HUVECs) via polyarginine- and RGD-modified bowties and evaluating the downstream effects on proliferation and tube formation. Our findings indicate that the bowtie elicits desired responses and may possess superior delivery properties compared to nondecorated dendrimeric materials. The bowtie system thereby provides a new design model for developing dendrimeric delivery vehicles for RNAi therapeutics. © 2012 American Chemical Society.

Zhang W.,Peking University | Zhang W.,National Engineering Laboratory for Regenerative and Implantable Medical Devices | Xu B.,National Engineering Laboratory for Regenerative and Implantable Medical Devices | Zhang Y.,General Hospital of Guangzhou Military Command | And 2 more authors.
Journal of Biomaterials and Tissue Engineering | Year: 2014

Peripheral nerve injury is a common traumatic illness in clinic, and long-gap injury in particular has been difficult to repair. In this study, a new type of biological nerve conduits with tunable diameters and lengths were fabricated from extracellular matrices (ECM) derived from porcine small intestinal submucosa. A peroneal nerve defect model was established by removing the left common peroneal nerve of pre-defined lengths in goats. The biological conduits were sutured in and their functions to repair 2 cm, 4 cm, 6 cm and 8 cm nerve defects were investigated for a 12 month period. Electrophysiological, histological, and TEM examinations showed normal nerve conductive velocities and regeneration of myelinated nerve fibers in 2 cm and 4 cm defects grafted with ECM-based conduits. The effects of these biological conduits on the repair of 2 cm and 4 cm nerve defects were comparable to those of allograft nerves. The repair function of nerve conduits was found to decrease with the defect lengths. The ECM-based nerve conduits may possess advantageous bioactive properties to support nerve tissue regeneration and have potential for future clinical use in long-gap nerve injury repair. © 2014 American Scientific Publishers All rights reserved.

Liu J.,Peking University | Gray W.D.,Peking University | Gray W.D.,Georgia Institute of Technology | Davis M.E.,Georgia Institute of Technology | And 3 more authors.
Interface Focus | Year: 2012

Dendrimers comprise a category of branched materials with diverse functions that can be constructed with defined architectural and chemical structures. When decorated with bioactive ligands made of peptides and saccharides through peripheral chemical groups, dendrimer conjugates are turned into nanomaterials possessing attractive binding properties with the cognate receptors. At the cellular level, bioactive dendrimer conjugates can interact with cells with avidity and selectivity, and this function has particularly stimulated interests in investigating the targeting potential of dendrimer materials for the design of drug delivery systems. In addition, bioactive dendrimer conjugates have so far been studied for their versatile capabilities to enhance stability, solubility and absorption of various types of therapeutics. This review presents a brief discussion on three aspects of the recent studies to use peptide- and saccharide-conjugated dendrimers for drug delivery: (i) synthesis methods, (ii) cell-and tissue-targeting properties and (iii) applications of conjugated dendrimers in drug delivery nanodevices. With more studies to elucidate the structure -function relationship of ligand-dendrimer conjugates in transporting drugs, the conjugated dendrimers hold promise to facilitate targeted delivery and improve drug efficacy for discovery and development of modern pharmaceutics. © 2012 The Royal Society.

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