Enhancing volumetric muscle loss (VML) recovery in a rat model using super durable hydrogels derived from bacteria.

Bacteria can be programmed to deliver natural materials with defined biological and mechanical properties for controlling cell growth and differentiation. Here, we present an elastic, resilient and bioactive polysaccharide derived from the extracellular matrix of Pantoea sp. BCCS 001. Specifically, it was methacrylated to generate a new photo crosslinkable hydrogel that we coined Pantoan Methacrylate or put simply PAMA. We have used it for the first time as a tissue engineering hydrogel to treat VML injuries in rats. The crosslinked PAMA hydrogel was super elastic with a recovery nearing 100 %, while mimicking the mechanical stiffness of native muscle. After inclusion of thiolated gelatin via a Michaelis reaction with acrylate groups on PAMA we could also guide muscle progenitor cells into fused and aligned tubes - something reminiscent of mature muscle cells. These results were complemented by sarcomeric alpha-actinin immunostaining studies. Importantly, the implanted hydrogels exhibited almost 2-fold more muscle formation and 50 % less fibrous tissue formation compared to untreated rat groups. In vivo inflammation and toxicity assays likewise gave rise to positive results confirming the biocompatibility of this new biomaterial system. Overall, our results demonstrate that programmable polysaccharides derived from bacteria can be used to further advance the field of tissue engineering. In greater detail, they could in the foreseeable future be used in practical therapies against VML.

Smart alginate inks for tissue engineering applications.

Amazing achievements have been made in the field of tissue engineering during the past decades. However, we have not yet seen fully functional human heart, liver, brain, or kidney tissue emerge from the clinics. The promise of tissue engineering is thus still not fully unleashed. This is mainly related to the challenges associated with producing tissue constructs with similar complexity as native tissue. Bioprinting is an innovative technology that has been used to obliterate these obstacles. Nevertheless, natural organs are highly dynamic and can change shape over time; this is part of their functional repertoire inside the body. 3D-bioprinted tissue constructs should likewise adapt to their surrounding environment and not remain static. For this reason, the new trend in the field is 4D bioprinting - a new method that delivers printed constructs that can evolve their shape and function over time. A key lack of methodology for printing approaches is the scalability, easy-to-print, and intelligent inks. Alginate plays a vital role in driving innovative progress in 3D and 4D bioprinting due to its exceptional properties, scalability, and versatility. Alginate's ability to support 3D and 4D printing methods positions it as a key material for fueling advancements in bioprinting across various applications, from tissue engineering to regenerative medicine and beyond. Here, we review the current progress in designing scalable alginate (Alg) bioinks for 3D and 4D bioprinting in a "dry"/air state. Our focus is primarily on tissue engineering, however, these next-generation materials could be used in the emerging fields of soft robotics, bioelectronics, and cyborganics.

The Manufacture of Unbreakable Bionics via Multifunctional and Self-Healing Silk-Graphene Hydrogels.

Biomaterials capable of transmitting signals over longer distances than those in rigid electronics can open new opportunities for humanity by mimicking the way tissues propagate information. For seamless mirroring of the human body, they also have to display conformability to its curvilinear architecture, as well as, reproducing native-like mechanical and electrical properties combined with the ability to self-heal on demand like native organs and tissues. Along these lines, a multifunctional composite is developed by mixing silk fibroin and reduced graphene oxide. The material is coined "CareGum" and capitalizes on a phenolic glue to facilitate sacrificial and hierarchical hydrogen bonds. The hierarchal bonding scheme gives rise to high mechanical toughness, record-breaking elongation capacity of ≈25 000%, excellent conformability to arbitrary and complex surfaces, 3D printability, a tenfold increase in electrical conductivity, and a fourfold increase in Young's modulus compared to its pristine counterpart. By taking advantage of these unique properties, a durable and self-healing bionic glove is developed for hand gesture sensing and sign translation. Indeed, CareGum is a new advanced material with promising applications in fields like cyborganics, bionics, soft robotics, human-machine interfaces, 3D-printed electronics, and flexible bioelectronics.

Flexible and Green Electronics Manufactured by Origami Folding of Nanosilicate-Reinforced Cellulose Paper.

Today's consumer electronics are made from nonrenewable and toxic components. They are also rigid, bulky, and manufactured in an energy-inefficient manner via CO2-generating routes. Though petroleum-based polymers such as polyethylene terephthalate and polyethylene naphthalate can address the rigidity issue, they have a large carbon footprint and generate harmful waste. Scalable routes for manufacturing electronics that are both flexible and ecofriendly (Fleco) could address the challenges in the field. Ideally, such substrates must incorporate into electronics without compromising device performance. In this work, we demonstrate that a new type of wood-based [nanocellulose (NC)] material made via nanosilicate (NS) reinforcement can yield flexible electronics that can bend and roll without loss of electrical function. Specifically, the NSs interact electrostatically with NC to reinforce thermal and mechanical properties. For instance, films containing 34 wt % of NS displayed an increased young's modulus (1.5 times), thermal stability (290 → 310 °C), and a low coefficient of thermal expansion (40 ppm/K). These films can also easily be separated and renewed into new devices through simple and low-energy processes. Moreover, we used very cheap and environmentally friendly NC from American Value Added Pulping (AVAP) technology, American Process, and therefore, the manufacturing cost of our NS-reinforced NC paper is much cheaper ($0.016 per dm-2) than that of conventional NC-based substrates. Looking forward, the methodology highlighted herein is highly attractive as it can unlock the secrets of Fleco electronics and transform otherwise bulky, rigid, and "difficult-to-process" rigid circuits into more aesthetic and flexible ones while simultaneously bringing relief to an already-overburdened ecosystem.

A Protein-Based, Water-Insoluble, and Bendable Polymer with Ionic Conductivity: A Roadmap for Flexible and Green Electronics.

Proteins present an ecofriendly alternative to many of the synthetic components currently used in electronics. They can therefore in combination with flexibility and electroactivity uncover a range of new opportunities in the field of flexible and green electronics. In this study, silk-based ionic conductors are turned into stable thin films by embedding them with 2D nanoclay platelets. More specifically, this material is utilized to develop a flexible and ecofriendly motion-sensitive touchscreen device. The display-like sensor can readily transmit light, is easy to recycle and can monitor the motion of almost any part of the human body. It also displays a significantly lower sheet resistance during bending and stretching regimes than the values typically reported for conventional metallic-based conductors, and remains fully operational after mechanical endurance testing. Moreover, it can operate at high frequencies in the kilohertz (kHz) range under both normal and bending modes. Notably, our new technology is available through a simple one-step manufacturing technique and can therefore easily be extended to large-scale fabrication of electronic devices.

Sericin grafted multifunctional curcumin loaded fluorinated graphene oxide nanomedicines with charge switching properties for effective cancer cell targeting.

Fluorinated graphene has recently gained much attention for cancer drug delivery, owing to its peculiar properties including high electronegativity difference, magnetic resonance imaging contrast agent, and the photothermal effect. However, the hydrophobic nature of fluorinated graphene greatly hinders its application as a biological material. Herein, a novel green method is reported for synthesis of a pH-sensitive charge-reversal and water-soluble fluorinated graphene oxide, modified with polyethyleneimine anchored to sericin-polypeptide (FPS). This nanocarrier was further loaded with curcumin (Cur), and characterized as a nanocarrier for anti-cancer drug delivery. The synthesized nanocarriers contain two different pH-sensitive amide linkages, which are negatively charged in blood pH (≈7.4) and can prolong circulation times. The amide linkages undergo hydrolysis once they reach the mildly acidic condition (pH≈6.5, corresponding to tumor extracellular matrix), and subsequently once reached the lower acidic condition (pH≈5.5, corresponded to endo/lysosomes microenvironment), the FPS charge can be switched to positive (≈+28 mV), which aids the nuclear release. This nanocarrier was designed to selectively enhance cell internalization and nuclear-targeted delivery of curcumin in HeLa, SkBr3 and PC-3 cancer cells. Moreover, FPS-Cur demonstrated high curcumin loading capacity, prolonged curcumin release and promotion of apoptosis in HeLa, SkBr3 and PC-3 cells. Therefore, with its pH-responsive charge-reversal properties, FPS-Cur would be a promising candidate for chemotherapy of cervical, breast and prostate cancers.