In situ forming and self-crosslinkable protein hydrogels for localized cancer therapy and topical wound healing.

Proteins, inherently biocompatible and biodegradable, face a challenge in forming stable hydrogels without external chemical crosslinkers. Here, we construct a ring-shaped trimeric SpyTag-fused Proliferating Cell Nuclear Antigen Protein (ST-PCNA) as a core protein building block, and a dumbbell-shaped tandem dimeric SpyCatcher (SC-SC) as a bridging component. Self-crosslinked PCNA/SC-SC Protein (2SP) hydrogels are successfully formed by simply mixing the solutions of ST-PCNA and SC-SC, without chemical crosslinkers.

Bioactive Microgels with Tunable Microenvironment as a 3D Platform to Guide the Complex Physiology of Hepatocellular Carcinoma Spheroids.

Miniaturized three-dimensional tissue models, such as spheroids, have become a highly useful and efficient platform to investigate tumor physiology and explore the effect of chemotherapeutic efficacy over traditional two-dimensional monolayer culture, since they can provide more in-depth analysis, especially in regards to intercellular interactions and diffusion. The development of most tumor spheroids relies on the high proliferative capacity and self-aggregation behavior of tumor cells. However, it often disregards the effect of microenvironmental factors mediated by extracellular matrix, which are indispensable components of tissue structure.

Multiscale Control of Nanofiber-Composite Hydrogel for Complex 3D Cell Culture by Extracellular Matrix Composition and Nanofiber Alignment.

In order to manipulate the complex behavior of cells in a 3-dimensional (3D) environment, it is important to provide the microenvironment that can accurately portray the complexity of highly anisotropic tissue structures. However, it is technically challenging to generate a complex microenvironment using conventional biomaterials that are mostly isotropic with limited bioactivity. In this study, the gelatin-hyaluronic acid hydrogel incorporated with aqueous-dispersible, short nanofibers capable of in situ alignment is developed to emulate the native heterogeneous extracellular matrix consisting of fibrous and non-fibrous components.

Microfluidics-assisted fabrication of natural killer cell-laden microgel enhances the therapeutic efficacy for tumor immunotherapy.

Recently, interest in cancer immunotherapy has increased over traditional anti-cancer therapies such as chemotherapy or targeted therapy. Natural killer (NK) cells are part of the immune cell family and essential to tumor immunotherapy as they detect and kill cancer cells. However, the disadvantage of NK cells is that cell culture is difficult.

Structural evaluation of Poly(lactic acid) degradation at standardized composting temperature of 58 degrees.

The accumulation of petroleum-based plastics on our planet is causing serious environmental pollution. Biodegradable plastics, promoted as eco-friendly solutions, hold the potential to address this issue. However, their impact on the environment and the mechanisms of their natural degradation remain inadequately understood.

Network of cyano-p-aramid nanofibres creates ultrastiff and water-rich hydrospongels.

The structure-property paradox of biological tissues, in which water-rich porous structures efficiently transfer mass while remaining highly mechanically stiff, remains unsolved. Although hydrogel/sponge hybridization is the key to understanding this phenomenon, material incompatibility makes this a challenging task. Here we describe hydrogel/sponge hybrids (hydrospongels) that behave as both ultrastiff water-rich gels and reversibly squeezable sponges.

Flexible, Biodegradable, and Wireless Magnetoelectric Paper for Simple In Situ Personalization of Bioelectric Implants.

Bioelectronic implants delivering electrical stimulation offer an attractive alternative to traditional pharmaceuticals in electrotherapy. However, achieving simple, rapid, and cost-effective personalization of these implants for customized treatment in unique clinical and physical scenarios presents a substantial challenge. This challenge is further compounded by the need to ensure safety and minimal invasiveness, requiring essential attributes such as flexibility, biocompatibility, lightness, biodegradability, and wireless stimulation capability.

Exploring stimuli-responsive elastin-like polypeptide for biomedicine and beyond: potential application as programmable soft actuators.

With the emergence of soft robotics, there is a growing need to develop actuator systems that are lightweight, mechanically compliant, stimuli-responsive, and readily programmable for precise and intelligent operation. Therefore, "smart" polymeric materials that can precisely change their physicomechanical properties in response to various external stimuli (e.g.

Ultrasound standing wave spatial patterning of human umbilical vein endothelial cells for 3D micro-vascular networks formation.

Generating functional and perfusable micro-vascular networks is an important goal for the fabrication of large and three-dimensional tissues. Up to now, the fabrication of micro-vascular networks is a complicated multitask involving several different factors such as time consuming, cells survival, micro-diameter vasculature and strict alignment. Here, we propose a technique combining multi-material extrusion and ultrasound standing wave forces to create a network structure of human umbilical vein endothelial cells within a mixture of calcium alginate and decellularized extracellular matrix.

Double-layered blood vessels over 3 mm in diameter extruded by the inverse-gravity technique.

One of the most promising techniques for treating severe peripheral artery disease is the use of cellular tissue-engineered vascular grafts (TEVGs). This study proposes an inverse-gravity (IG) extrusion technique for creating long double-layered cellular TEVGs with diameters over 3 mm. A three-layered coaxial laminar hydrogel flow in an 8 mm-diameter pipe was realised simply by changing the extrusion direction of the hydrogel from being aligned with the direction of gravity to against it.

Emerging Technology of Nanofiber-Composite Hydrogels for Biomedical Applications.

Hydrogels and nanofibers have been firmly established as go-to materials for various biomedical applications. They have been mostly utilized separately, rarely together, because of their distinctive attributes and shortcomings. However, the potential benefits of integrating nanofibers with hydrogels to synergistically combine their functionalities while attenuating their drawbacks are increasingly recognized.

Manipulating Physicochemical Properties of Biosensor Platform with Polysuccinimide-Silica Nanocomposite for Enhanced Protein Detection.

As point-of-care testing (POCT) is becoming the new paradigm of medical diagnostics, there is a growing need to develop reliable POCT devices that can be conveniently operated in a minimally invasive manner. However, the clinical potential of POCT diagnostics is yet to be realized, mainly due to the limited and inconsistent amount of collected samples on these devices, undermining their accuracy. This study proposes a new biosensing platform modified with a functional polysuccinimide (PSI)-silica nanoparticle (SNP) composite system that can substantially increase the protein conjugation efficiency by modulating physicochemical interaction with proteins by several hundred percent from an unmodified device.

Tunable Physicomechanical and Drug Release Properties of In Situ Forming Thermoresponsive Elastin-like Polypeptide Hydrogels.

With the continued advancement in the design and engineering of hydrogels for biomedical applications, there is a growing interest in imparting stimuli-responsiveness to the hydrogels in order to control their physicomechanical properties in a more programmable manner. In this study, an in situ forming hydrogel is developed by cross-linking alginate with an elastin-like polypeptide (ELP). Lysine-rich ELP synthesized by recombinant DNA technology is reacted with alginate presenting an aldehyde via Schiff base formation, resulting in facile hydrogel formation under physiological conditions.

Precision Control of Programmable Actuation of Thermoresponsive Nanocomposite Hydrogels with Multilateral Engineering.

Hydrogels capable of stimuli-responsive deformation are widely explored as intelligent actuators for diverse applications. It is still a significant challenge, however, to "program" these hydrogels to undergo highly specific and extensive shape changes with precision, because the mechanical properties and deformation mechanism of the hydrogels are inherently coupled. Herein, two engineering strategies are simultaneously employed to develop thermoresponsive poly(N-isopropyl acrylamide) (PNIPAm)-based hydrogels capable of programmable actuation.

Multiscale Engineering of Nanofiber-Aerogel Composite Nanogenerator with Tunable Triboelectric Performance Based on Multifunctional Polysuccinimide.

Multiscale polymer engineering, involving chemical modification to control their triboelectric polarities as well as physicomechanical modification to maximize charge transfer and structural durability, is paramount to developing a high-performance triboelectric nanogenerator (TENG). This report introduces a highly efficient and comprehensive strategy to engineer high-performance TENG based on multifunctional polysuccinimide (PSI). With the ability of PSI to undergo facile nucleophilic addition with amines, sodium sulfate and quaternary ammonium chlorides having opposite charged groups are conjugated to PSI in varying densities.

Mechanotopography-Driven Design of Dispersible Nanofiber-Laden Hydrogel as a 3D Cell Culture Platform for Investigating Tissue Fibrosis.

Fibrosis is one of the most frequent occurrences during one's lifetime, identified by various physiological changes including, most notably, excessive deposition of extracellular matrix (ECM). Despite its physiological importance, it is still a significant challenge to conduct a systematic investigation of tissue fibrosis, mainly due to the lack of in vitro 3D tissue model that can accurately portray the characteristic features of fibrotic events. Herein, a hybrid hydrogel system incorporating dispersible nanofibers is developed to emulate highly collagenous deposits formed within a fibrotic tissue leading to altered mechanotopographical properties.

Synergistic control of mechanics and microarchitecture of 3D bioactive hydrogel platform to promote the regenerative potential of engineered hepatic tissue.

Culturing autologous cells with therapeutic potential derived from a patient within a bioactive scaffold to induce functioning tissue formation is considered the ideal methodology towards realizing patient-specific regenerative medicine. Hydrogels are often employed as the scaffold material for this purpose mainly for their tunable mechanical and diffusional properties as well as presenting cell-responsive moieties. Herein, a two-fold strategy was employed to control the physicomechanical properties and microarchitecture of hydrogels to maximize the efficacy of engineered hepatic tissues.

Programmable multilayer printing of a mechanically-tunable 3D hydrogel co-culture system for high-throughput investigation of complex cellular behavior.

Hydrogels are widely used as a 3D cell culture platform, as they can be tailored to provide suitable microenvironments to induce cellular phenotypes with physiological significance. Hydrogels are especially deemed attractive as a co-culture platform, in which two or more different types of cells are cultured together in close proximity, since the spatial distribution of different cell types can be rendered possible by advanced microfabrication schemes. Herein, programmable multilayer photolithography is employed to develop a 3D hydrogel-based co-culture system in an efficient and scalable manner, which consists of an inner microgel array containing one cell type covered by an outer hydrogel overlay containing another cell type.

Dual-functional alginate crosslinker: Independent control of crosslinking density and cell adhesive properties of hydrogels via separate conjugation pathways.

Alginate is an abundant natural polysaccharide widely utilized in various biomedical applications. Alginate also possesses numerous hydroxyl and carboxylate functional groups that allow chemical modifications to introduce different functionalities. However, it is difficult to apply various chemical reactions to alginate due to limited solubility in organic solvents.

Graft Architecture Guided Simultaneous Control of Degradation and Mechanical Properties of In Situ Forming and Fast Dissolving Polyaspartamide Hydrogels.

Polyaspartamide, derived from polysuccinimide (PSI), has the advantage of conveniently presenting desired functional groups by ring-opening addition of amine-based nucleophiles to the succinimidyl ring moieties of PSI. Using diamines with varying lengths of poly(ethylene glycol) linker, polyaspartamide presenting amine groups with controllable grafting density and length, namely, poly(2-hydroxyethyl aspartamide)--amino-poly(ethylene glycol) (PHEA-PEGAm) could be synthesized. This PHEA-PEGAm was then used to develop in situ forming hydrogels by Schiff base formation with aldehyde-containing alginate (Alg-ALD).

Cell subtype-dependent formation of breast tumor spheroids and their variable responses to chemotherapeutics within microfluidics-generated 3D microgels with tunable mechanics.

Tumor spheroids have been considered valuable miniaturized three dimensional (3D) tissue models for fundamental biological investigation as well as drug screening applications. Most tumor spheroids are generated utilizing the inherent aggregate behavior of tumor cells, and the effect of microenvironmental factors such as extracellular matrix (ECM) on tumor spheroid formation has not been extensively elucidated to date. Herein, uniform-sized spherical microgels encapsulated with different subtypes of breast tumor cells, based on tumor aggressiveness, are developed by flow-focusing microfluidics technology.

In situ facile-forming chitosan hydrogels with tunable physicomechanical and tissue adhesive properties by polymer graft architecture.

In situ forming hydrogels generated upon spontaneous and biocompatible reaction under physiological conditions are widely investigated as injectable and implantable biomaterials. However, it is still a significant challenge to control their mechanics while maintaining their gelation behavior, due to the interdependency between gelation kinetics and mechanics. Herein, physicomechanical properties of in situ forming chitosan hydrogels via Schiff base formation are tuned in a wide range, while maintaining gelation kinetics, via polymer graft architecture.

Enhanced mechanical and electrical properties of heteroscaled hydrogels infused with aqueous-dispersible hybrid nanofibers.

Despite the widespread use as platforms for various biomedical applications, engineering hydrogels to impart multifunctionality and control physical properties, while closely mimicking the native cellular microenvironment, is still a significant challenge. Herein, nanofibers consisting of hydrophilic and photocrosslinkable biopolymer and conductive polymer (i.e.

Implementation of Combinatorial Genetic and Microenvironmental Engineering to Microbial-Based Field-Deployable Microbead Biosensors for Highly Sensitive and Remote Chemical Detection.

Bioreporters, microbial species genetically engineered to provide measurable signals in response to specific chemicals, have been widely investigated as sensors for biomedical and environmental monitoring. More specifically, the bioreporter encapsulated within a biocompatible material, such as a hydrogel that can provide a suitable microenvironment for its prolonged activity as well as efficient scalable production, has been viewed as a more broadly applicable mode of biosensors. In this study, alginate-based microbeads encapsulated with the bacterial bioreporter capable of expressing green fluorescence protein in response to nitro compounds (e.

Comprehensive tuning of bioadhesive properties of polydimethylsiloxane (PDMS) membranes with controlled porosity.

Polydimethylsiloxane (PDMS)-based elastomers have become the de facto platform for various biomedical applications. But the stable attachment of biomolecules to PDMS for more robust and long-term performance of the PDMS-based devices has been a significant challenge, owing to its unique physical properties (e.g.