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AimDendrimers dendritic structural design holds vast promises, predominantly for drug delivery, owing to their unique properties. Dendritic architecture is widespread topology found in nature and offers development of specific properties of chemical substances. Dendrimers are an ideal delivery vehicle candidate for open study of the effects of polymer size, charge, and composition on biologically relevant properties such as lipid bilayer interactions, cytotoxicity, bio-distribution, internalization, blood plasma retention time, and filtration. This article reviews role of dendrimers in advanced drug delivery and biomedical applications.

Periodontitis is a prevalent chronic, destructive inflammatory disease affecting tooth-supporting tissues in humans. Guided tissue regeneration strategies are widely utilized for periodontal tissue regeneration generally by using a periodontal membrane. The main role of these membranes is to establish a mechanical barrier that prevents the apical migration of the gingival epithelium and hence allowing the growth of periodontal ligament and bone tissue to selectively repopulate the root surface. Currently available membranes have limited bioactivity and regeneration potential. To address such challenges, an osteoconductive, antibacterial, and flexible poly(caprolactone) (PCL) composite membrane containing zinc oxide (ZnO) nanoparticles is developed. The membranes are fabricated through electrospinning of PCL and ZnO particles. The physical properties, mechanical characteristics, and in vitro degradation of the engineered membrane are studied in detail. Also, the osteoconductivity and antibacterial properties of the developed membrane are analyzed in vitro. Moreover, the functionality of the membrane is evaluated with a rat periodontal defect model. The results confirmed that the engineered membrane exerts both osteoconductive and antibacterial properties, demonstrating its great potential for periodontal tissue engineering.

More than 90% of cancer-related deaths can be attributed to the occurrence of metastatic diseases. Recent studies have highlighted the importance of the multicellular, biochemical and biophysical stimuli from the tumor microenvironment during carcinogenesis, treatment failure, and metastasis. Therefore, there is a need for experimental platforms that are able to recapitulate the complex pathophysiological features of the metastatic microenvironment. Recent advancements in biomaterials, microfluidics, and tissue engineering have led to the development of living multicellular microculture systems, which are maintained in controllable microenvironments and function with organ level complexity. The applications of these "on-chip" technologies for detection, separation, characterization and three dimensional (3D) propagation of cancer cells have been extensively reviewed in previous works. In this contribution, we focus on integrative microengineered platforms that allow the study of multiple aspects of the metastatic microenvironment, including the physicochemical cues from the tumor associated stroma, the heterocellular interactions that drive trans-endothelial migration and angiogenesis, the environmental stresses that metastatic cancer cells encounter during migration, and the physicochemical gradients that direct cell motility and invasion. We discuss the application of these systems as in vitro assays to elucidate fundamental mechanisms of cancer metastasis, as well as their use as human relevant platforms for drug screening in biomimetic microenvironments. We then conclude with our commentaries on current progress and future perspectives of microengineered systems for fundamental and translational cancer research.

We demonstrate ultrastrong and flexible hydrogels by self-assembling chitin nanofiber in the presence of gelatin methacryloyl. We tune the mechanical properties of the hydrogel with chitin nanofiber content and show proof-of-concept applications in engineering vascular tissue.

We demonstrate the formation of ultrastrong and flexible hydrogels via self-assembly of chitin nanofibers in the presence of gelatin methacryloyl. We tune the mechanical properties of the hydrogel using the chitin nanofiber content and show proof-of-concept applications in engineering vascular tissues. [ABSTRACT FROM AUTHOR]

Bacterial nanocellulose (BNC) is a durable, flexible, and dynamic biomaterial capable of serving a wide variety of fields, sectors, and applications within biotechnology, healthcare, electronics, agriculture, fashion, and others. BNC is produced spontaneously in carbohydrate-rich bacterial culture media, forming a cellulosic pellicle via a nanonetwork of fibrils extruded from certain genera. Herein, we demonstrate engineering BNC-based scaffolds with tunable physical and mechanical properties through postprocessing. Human skeletal muscle myoblasts (HSMMs) were cultured on these scaffolds, and in vitro electrical stimulation was applied to promote cellular function for tissue engineering applications. We compared physiologic maturation markers of human skeletal muscle myoblast development using a 2.5-dimensional culture paradigm in fabricated BNC scaffolds, compared to two-dimensional (2D) controls. We demonstrate that the culture of human skeletal muscle myoblasts on BNC scaffolds developed under electrical stimulation produced highly aligned, physiologic morphology of human skeletal muscle myofibers compared to unstimulated BNC and standard 2D culture. Furthermore, we compared an array of metrics to assess the BNC scaffold in a rigorous head-to-head study with commercially available, clinically approved matrices, Kerecis Omega3 Wound Matrix (Marigen) and Phoenix as well as a gelatin methacryloyl (GelMA) hydrogel. The BNC scaffold outcompeted industry standard matrices as well as a 20% GelMA hydrogel in durability and sustained the support of human skeletal muscle myoblasts in vitro. This work offers a robust demonstration of BNC scaffold cytocompatibility with human skeletal muscle cells and sets the basis for future work in healthcare, bioengineering, and medical implant technological development.

Real-time continuous monitoring of non-cognitive markers is crucial for the early detection and management of chronic conditions. Current diagnostic methods are often invasive and not suitable for at-home monitoring. An elastic, adhesive, and biodegradable hydrogel-based wearable sensor with superior accuracy and durability for monitoring real-time human health is developed. Employing a supramolecular engineering strategy, a pseudo-slide-ring hydrogel is synthesized by combining polyacrylamide (pAAm), β-cyclodextrin (β-CD), and poly 2-(acryloyloxy)ethyltrimethylammonium chloride (AETAc) bio ionic liquid (Bio-IL). This novel approach decouples conflicting mechano-chemical effects arising from different molecular building blocks and provides a balance of mechanical toughness (1.1 × 10 6 Jm -3 ), flexibility, conductivity (≈0.29 S m -1 ), and tissue adhesion (≈27 kPa), along with rapid self-healing and remarkable stretchability (≈3000%). Unlike traditional hydrogels, the one-pot synthesis avoids chemical crosslinkers and metallic nanofillers, reducing cytotoxicity. While the pAAm provides mechanical strength, the formation of the pseudo-slide-ring structure ensures high stretchability and flexibility. Combining pAAm with β-CD and pAETAc enhances biocompatibility and biodegradability, as confirmed by in vitro and in vivo studies. The hydrogel also offers transparency, passive-cooling, ultraviolet (UV)-shielding, and 3D printability, enhancing its practicality for everyday use. The engineered sensor demonstratesimproved efficiency, stability, and sensitivity in motion/haptic sensing, advancing real-time human healthcare monitoring., (© 2024 Wiley‐VCH GmbH.)

The design of adhesive and conductive soft hydrogels using biopolymers with tunable mechanical properties has received significant interest in the field of wearable sensors for detecting human motions. These hydrogels are primarily fabricated through the modification of biopolymers to introduce cross-linking sites, the conjugation of adhesive components, and the incorporation of conductive materials into the hydrogel network. The development of a multifunctional copolymer that integrates adhesive and conductive properties within a single polymer chain with suitable cross-linking sites eliminates the need for biopolymer modification and the addition of extra conductive and adhesive components. In this study, we synthesized a copolymer based on poly([2-(methacryloyloxy)ethyl] trimethylammonium chloride- co -dopamine methacrylamide) (p(METAC-DMA)) using a controlled radical polymerization, allowing for the efficient conjugation of both adhesive and conductive units within a single polymer chain. Subsequently, our multifunctional hydrogel named Gel-MD was fabricated by mixing the p(METAC-DMA) copolymer with non-modified gelatin in which cross-linking took place in an oxidative environment. We confirmed the biocompatibility of the Gel-MD hydrogel through in vitro studies using NIH 3T3 cells as well as in vivo subcutaneous implantation in rats. Furthermore, the Gel-MD hydrogel was effective and sensitive in detecting various human motions, making it a promising wearable sensor for health monitoring and diagnosis.

In situ-forming hydrogels that possess the ability to be injected in a less invasive manner and mimic the biochemical composition and microarchitecture of the native cartilage extracellular matrix are desired for cartilage tissue engineering. Besides, gelation time and stiffness of the hydrogel are two interdependent factors that affect cells' distribution and fate and hence need to be optimized. This study presented a bioinspired in situ-forming hydrogel composite of hyaluronic acid (HA), chondroitin sulfate (CS), and collagen short nanofiber (CSNF). HA and CS were functionalized with aldehyde and amine groups to form a gel through a Schiff-base reaction. CSNF was fabricated via electrospinning, followed by fragmentation by ultrasonics. Gelation time (11-360 s) and compressive modulus (1.4-16.2 kPa) were obtained by varying the concentrations of CS, HA, CSNFs, and CSNFs length. The biodegradability and biocompatibility of the hydrogels with varying gelation and stiffness were also assessed in vitro and in vivo. At three weeks, the assessment of hydrogels' chondrogenic differentiation also yields varying levels of chondrogenic differentiation. The subcutaneous implantation of the hydrogels in a mouse model indicated no severe inflammation. Results demonstrated that the injectable CS/HA@CSNF hydrogel was a promising hydrogel for tissue engineering and cartilage regeneration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Urethral conditions affect children and adults, increasing the risk of urinary tract infections, voiding and sexual dysfunction, and renal failure. Current tissue replacements differ from healthy urethral tissues in structural and mechanical characteristics, causing high risk of postoperative complications. 3D bioprinting can overcome these limitations through the creation of complex, layered architectures using materials with location-specific biomechanical properties. This review highlights prior research and describes the potential for these emerging technologies to address ongoing challenges in urethral tissue engineering, including biomechanical and structural mismatch, lack of individualized repair solutions, and inadequate wound healing and vascularization. In the future, the integration of 3D bioprinting technology with advanced biomaterials, computational modeling, and 3D imaging could transform personalized urethral surgical procedures., Competing Interests: Declaration of interests N.A., is a member of the journal’s advisory board and affirms that this affiliation did not influence the idea, execution, or interpretation of the article. N.A. holds equity in GelMEDIX Inc.; R.S. holds equity in Protean Surgical Instruments. The remaining authors declare no interests., (Published by Elsevier Ltd.)

Bioadhesives with antimicrobial properties enable easier and safer treatment of wounds as compared to the traditional methods such as suturing and stapling. Composed of natural or synthetic polymers, these bioadhesives seal wounds and facilitate healing while preventing infections through the activity of locally released antimicrobial drugs, nanocomponents, or inherently antimicrobial polers. Although many different materials and strategies are employed to develop antimicrobial bioadhesives, the design of these biomaterials necessitates a prudent approach as achieving all the required properties including optimal adhesive and cohesive properties, biocompatibility, and antimicrobial activity can be challenging. Designing antimicrobial bioadhesives with tunable physical, chemical, and biological properties will shed light on the path for future advancement of bioadhesives with antimicrobial properties. In this review, the requirements and commonly used strategies for developing bioadhesives with antimicrobial properties are discussed. In particular, different methods for their synthesis and their experimental and clinical applications on a variety of organs are reviewed. Advances in the design of bioadhesives with antimicrobial properties will pave the way for a better management of wounds to increase positive clinical outcomes., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Controlling traumatic bleeding from damaged internal organs while effectively sealing the wound is critical for saving the lives of patients. Existing bioadhesives suffer from blood incompatibility, insufficient adhesion to wet surfaces, weak mechanical properties, and complex application procedures. Here, we engineered a ready-to-use hemostatic bioadhesive with ultra-strengthened mechanical properties and fatigue resistance, robust adhesion to wet tissues within a few seconds of gentle pressing, deformability to accommodate physiological function and action, and the ability to stop bleeding efficiently. The engineered hydrogel, which demonstrated high elasticity (>900%) and toughness (>4600 kJ/m 3 ), was formed by fine-tuning a series of molecular interactions and crosslinking mechanisms involving N-hydroxysuccinimide (NHS) conjugated alginate (Alg-NHS), poly (ethylene glycol) diacrylate (PEGDA), tannic acid (TA), and Fe 3+ ions. Dual adhesive moieties including mussel-inspired pyrogallol/catechol and NHS synergistically enhanced wet tissue adhesion (>400 kPa in a wound closure test). In conjunction with physical sealing, the high affinity of TA/Fe 3+ for blood could further augment hemostasis. The engineered bioadhesive demonstrated excellent in vitro and in vivo biocompatibility as well as improved hemostatic efficacy as compared to commercial Surgicel®. Overall, the hydrogel design strategy described herein holds great promise for overcoming existing obstacles impeding clinical translation of engineered hemostatic bioadhesives., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Designing adhesive hydrogels with optimal properties for the treatment of injured tissues is challenging due to the tradeoff between material stiffness and toughness while maintaining adherence to wet tissue surfaces. In most cases, bioadhesives with improved mechanical strength often lack an appropriate elastic compliance, hindering their application for sealing soft, elastic, and dynamic tissues. Here, we present a novel strategy for engineering tissue adhesives in which molecular building blocks are manipulated to allow for precise control and optimization of the various aforementioned properties without any tradeoffs. To introduce tunable mechanical properties and robust tissue adhesion, the hydrogel network presents different modes of covalent and noncovalent interactions using N -hydroxysuccinimide ester (NHS) conjugated alginate (Alg-NHS), poly (ethylene glycol) diacrylate (PEGDA), tannic acid (TA), and Fe 3+ ions. Through combining and tuning different molecular interactions and a variety of crosslinking mechanisms, we were able to design an extremely elastic (924%) and tough (4697 kJ/m 3 ) multifunctional hydrogel that could quickly adhere to wet tissue surfaces within 5 s of gentle pressing and deform to support physiological tissue function over time under wet conditions. While Alg-NHS provides covalent bonding with the tissue surfaces, the catechol moieties of TA molecules synergistically adopt a mussel-inspired adhesive mechanism to establish robust adherence to the wet tissue. The strong adhesion of the engineered bioadhesive patch is showcased by its application to rabbit conjunctiva and porcine cornea. Meanwhile, the engineered bioadhesive demonstrated painless detachable characteristics and in vitro biocompatibility. Additionally, due to the molecular interactions between TA and Fe 3+ , antioxidant and antibacterial properties required to support the wound healing pathways were also highlighted. Overall, by tuning various molecular interactions, we were able to develop a single-hydrogel platform with an "all-in-one" multifunctionality that can address current challenges of engineering hydrogel-based bioadhesives for tissue repair and sealing., (© 2023 The Authors.)

Mussel-inspired catechol-functionalization of degradable natural biomaterials has garnered significant interest as an approach to achieve bioadhesion for sutureless wound closure. However, conjugation capacity in standard coupling reactions, such as carbodiimide chemistry, is limited by low yield and lack of abundant conjugation sites. Here, a simple oxidative polymerization step before conjugation of catechol-carrying molecules (i.e., 3,4-dihydroxy-l-phenylalanine, l-DOPA) as a potential approach to amplify catechol function in bioadhesion of natural gelatin biomaterials is proposed. Solutions of gelatin modified with poly(l-DOPA) moieties (GelDOPA) are characterized by faster physical gelation and increased viscosity, providing better wound control on double-curved tissue surfaces compared to those of l-DOPA-conjugated gelatin. Physical hydrogels treated topically with low concentrations of NaIO 4 solutions are crosslinked on-demand via through-thickness diffusion. Poly(l-DOPA) conjugates enhance crosslinking density compared to l-DOPA conjugated gelatin, resulting in lower swelling and enhanced cohesion in physiological conditions. Together with cohesion, more robust bioadhesion at body temperature is achieved by poly(l-DOPA) conjugates, exceeding those of commercial sealants. Further, poly(l-DOPA) motifs introduced photothermal responsiveness via near-infrared (NIR) irradiation for controlled drug release and potential applications in photothermal therapy. The above functionalities, along with antibacterial activity, render the proposed approach an effective biomaterial design strategy for wound closure applications., (© 2023 Wiley-VCH GmbH.)

Ocular inflammation is commonly associated with eye disease or injury. Effective and sustained ocular delivery of therapeutics remains a challenge due to the eye physiology and structural barriers. Herein, we engineered a photocrosslinkable adhesive patch (GelPatch) incorporated with micelles (MCs) loaded with Loteprednol etabonate (LE) for delivery and sustained release of drug. The engineered drug loaded adhesive hydrogel, with controlled physical properties, provided a matrix with high adhesion to the ocular surfaces. The incorporation of MCs within the GelPatch enabled solubilization of LE and its sustained release within 15 days. In vitro studies showed that MC loaded GelPatch supported cell viability and growth. In addition, subcutaneous implantation of the MC loaded GelPatch in rats confirmed its in vivo biocompatibility and stability within 28 days. This non-invasive, adhesive, and biocompatible drug eluting patch can be used as a matrix for the delivery and sustained release of hydrophobic drugs., Competing Interests: Competing interests: N.A. and R.D. hold equity in GelMEDIX Inc.