Hierarchically Inverse Opal Porous Scaffolds from Droplet Microfluidics for Biomimetic 3D Cell Co-Culture

With the advantages of better mimicking the specificity of natural tissues,three-dimensional(3D)cell culture plays a major role in drug development,toxicity testing,and tissue engineering.However,existing scaffolds or microcarriers for 3D cell culture are often limited in size and show suboptimal performance in simulating the vascular complexes of living organisms.Therefore,we present a novel hierarchically inverse opal porous scaffold made via a simple microfluidic approach for promoting 3D cell co-culture techniques.The designed scaffold is constructed using a combined concept involving an emulsion droplet template and inert polymer polymerization.This work demonstrates that the resultant scaffolds ensure a sufficient supply of nutrients during cell culture,so as to achieve large-volume cell culture.In addition,by serially planting different cells in the scaffold,a 3D co-culture system of endothelial-cellencapsulated hepatocytes can be developed for constructing certain functional tissues.It is also demonstrated that the use of the proposed scaffold for a co-culture system helps hepatocytes to maintain specific in vivo functions.These hierarchically inverse opal scaffolds lay the foundation for 3D cell culture and even the construction of biomimetic tissues.

Antibacterial and angiogenic chitosan microneedle array patch for promoting wound healing

A patch with the capability of avoiding wound infection and promoting tissue remolding is of great value for wound healing.In this paper,we develop a biomass chitosan microneedle array(CSMNA)patch integrated with smart responsive drug delivery for promoting wound healing.Chitosan possesses many outstanding features such as the natural antibacterial property and has been widely utilized for wound healing.Besides,the microstructure of microneedles enables the effective delivery of loaded drugs into the target area and avoids the excessive adhesion between the skin and the patch.Also,vascular endothelial growth factor(VEGF)is encapsulated in the micropores of CSMNA by temperature sensitive hydrogel.Therefore,the smart release of the drugs can be controllably realized via the temperature rising induced by the inflammation response at the site of wounds.It is demonstrated that the biomass CSMNA patch can promote inflammatory inhibition,collagen deposition,angiogenesis,and tissue regeneration during the wound closure.Thus,this versatile CSMNA patch is potentially valuable for wound healing in clinical applications.

Chinese herb microneedle patch for wound healing

Traditional Chinese medicine and Chinese herbs have a demonstrated value for disease therapy and sub-health improvement.Attempts in this area tend to develop new forms to make their applications more convenient and wider.Here,we propose a novel Chinese herb microneedle(CHMN)patch by integrating the herbal extracts,Premna microphylla and Centella asiatica,with microstructure of microneedle for wound healing.Such path is composed of sap extracted from the herbal leaves via traditional kneading method and solidified by plant ash derived from the brine induced process of tofu in a well-designed mold.Because the leaves of the Premna microphylla are rich in pectin and various amino acids,the CHMN could be imparted with medicinal efficacy of heat clearing,detoxicating,detumescence and hemostatic.Besides,with the excellent pharmaceutical activity of Asiatic acid extracted from Centella asiatica,the CHMN is potential in promoting relevant growth factor genes expression in fibroblasts and showing excellent performance in anti-oxidant,anti-inflammatory and anti-bacterial activity.Taking advantages of these pure herbal compositions,we have demonstrated that the derived CHMN was with dramatical achievement in anti-bacteria,inhibiting inflammatory,collagen deposition,angiogenesis and tissue reconstruction during the wound closure.These results indicate that the integration of traditional Chinese herbs with progressive technologies will facilitate the development and promotion of traditional Chinese medicine in modern society.

Supramolecular G-quadruplex hydrogels:Bridging fabrication to biomedical application

G-quadruplex hydrogel is a class of self-assembled supramolecular hydrogel formed by guanine derivatives.As a biomimetic hydrogel,G-quadruplex hydrogels demonstrate wide biomedical applications,such as drug delivery,tissue engineering,and biosensing.The advantages of using G-quadruplex hydrogels include adequate biocompatibility and biodegradability,tunable multifunctionality,and cost-effective and large-scalable fabrication process.In this review,we focus on recent progress in the fabrication and characterization of G-quadruplex hydrogels to help readers understand the principles of G-quadruplex hydrogel formation.Meanwhile,the applications of G-quadruplex hydrogels in the biomedical area are discussed,aiming to pave the way for downward clinical or industry translation.The development of G-quadruplex hydrogel is still in its infancy.We hope this review will boost the development of this area and that more applications of G-quadruplex hydrogel will be developed.

Smart Microneedles for Therapy and Diagnosis

Microneedles represent a cutting-edge and idea-inspiring technology in biomedical engineering,which have attracted increasing attention of scientific researchers and medical staffs.Over the past decades,numerous great achievements have been made.The fabrication process of microneedles has been simplified and becomes more precise,easy-to-operate,and reusable.Besides,microneedles with various features have been developed and the microneedle materials have greatly expanded.In recent years,efforts have been focused on generating smart microneedles by endowing them with intriguing functions such as adhesion ability,responsiveness,and controllable drug release.Such improvements enable the microneedles to take an important step in practical applications including household drug delivery devices,wearable biosensors,biomedical assays,cell culture,and microfluidic chip analysis.In this review,the fabrication strategies,distinctive properties,and typical applications of the smart microneedles are discussed.Recent accomplishments,remaining challenges,and future prospects are also presented.

Responsive Inverse Opal Scaffolds with Biomimetic Enrichment Capability for Cell Culture

Three-dimensional(3D)porous scaffolds have a demonstrated value for tissue engineering and regenerative medicine.Inspired by the predation processes of marine predators in nature,we present new photocontrolled shrinkable inverse opal graphene oxide(GO)hydrogel scaffolds for cell enrichment and 3D culture.The scaffolds with adjustable pore sizes and morphologies were created using a GO and N-isopropylacrylamide dispersed solution as a continuous phase of microfluidic emulsions for polymerizing and replicating.Because of the interconnected porous structures and the remotely controllable volume responsiveness of the scaffolds,the suspended cells could be enriched into the inner spaces of the scaffolds through predator-like swallowing and discharging processes.Hepatocyte cells concentrated in the scaffold pores could form denser 3D spheroids more quickly via the controlled compression force caused by the shrinking of the dynamic scaffolds.More importantly,with a program of scaffold enrichment with different cells,an unprecedented 3D multilayer coculture system of endothelial-cellencapsulated hepatocytes and fibroblasts could be generated for applications such as liver-on-a-chip and bioartificial liver.It was demonstrated that the resultant multicellular system offered significant improvements in hepatic functions,such as albumin secretion,urea synthesis,and cytochrome P450 expression.These features of our scaffolds make them highly promising for the biomimetic construction of various physiological and pathophysiological 3D tissue models,which could be used for understanding tissue level biology and in vitro drug testing applications.

Ellipsoidal porous patch with anisotropic cell inducing ability for inhibiting skin scar formation

Scar formation has always been a difficult point to overcome in the field of clinical wound care.Here,we present an ellipsoidal porous patch with cell inducing ability for inhibiting scar formation.The patch was prepared by stretching a poly(lactic-co-glycolic acid)(PLGA)inverse opal film at the glass transition temperature to form a neatly arranged three-dimensional ellipsoidal porous structure.Such anisotropic structure showed dramatic capability in directing cell growth and arrangement by reconstructing cell morphology.Besides,the prolifera-tion of cells growing on the stretched patch was significantly suppressed without cell cytotoxicity.In addition,benefitting from the abundant and connected nanopores,the patch could be imparted with a potent ability to promote cell migration by encapsulating fibroblast growth factor 2(FGF2)via the second filling of functional gelatin methacryloyl(GelMA)hydrogel into its scaffold.In a typical scar model,we have demonstrated that the resultant patch performed well in inhibiting scar formation characterized by inhibiting the excessive proliferation of fibroblasts,decreasing the deposition of type I collagen,reducing the scar index and achieved complete tissue reconstruction.These results indicate the anisotropic inverse opal patch has an excellent application prospect in inhibiting scar formation during wound repair.

Living Materials for Life Healthcare

CONSPECTUS:Living material is a type of composite material with living elements integrated into nonliving components.It combines the advantages of both living cells and nonliving substances and takes advantage of advanced fabrication techniques.Living materials is an emerging new paradigm at the frontiers of materials research.It addresses an intriguing question of how to let materials show life-like capabilities and function in an integrative and programmable way.Of all of the capability and application aspects of living materials,the one related to human health is the most intriguing since it implies that that materials could be made by life and used for life.Specifically,living materials exploit the merits of cells in that they can respond to environmental variables,synthesize functional molecules,and span multiple length scales.At the same time,the abundant coordination between live and nonliving elements opens infinite possibilities for diverse structural and functional features.The resultant biohybrid materials are thus endowed with novel functions that recapitulate or even surpass their natural candidates and ultimately shed new light on biodiagnostics and biotherapeutics to address human health concerns.In this Account,we present a concise summary and analysis of living materials and bring it into the context of addressing life healthcare concerns.We start with the fabrication of living materials,including the engineering of living elements and the manufacturing of biohybrid composites through advanced technologies,particularly micropatterning,microfluidics,and threedimensional(3D)printing.We then shift to the properties and capacities of living materials,such as autonomous motion,sensing and actuation,and highly sensitive detection.On the basis of these,we show,by representative examples,the healthcare-oriented applications of living materials in both diagnostic and biotherapeutic aspects,including biohybrid sensors and actuators,cell-powered robotics,organ-on-a-chip platforms,wearable devices,smart delivery vehicles,cell therapy,and tissue engineering.Despite the exciting achievements of living materials,challenges remain in the precise manipulation of the properties of living materials;therefore,we provide our insight for future directions in this burgeoning field with respect to both fundamental research and technical innovation.The former concerns a comprehensive understanding of spatiotemporal coordination between living and nonliving components as well as the heterogeneous properties of the biohybrid materials.The latter looks at precise gene editing of living elements,multiscale manufacturing of cell-involved entities,and the incorporation of signal-transducing units for creating advanced living devices.With extensive multidisciplinary cooperation in the aforementioned areas,we expect living materials to stand out at the forefront of material science and engineering and take a giant leap forward to improve human health.