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The development of precise and personalized medicine requires novel formulation strategies to deliver the therapeutic payloads to the pathological tissues, producing enhanced therapeutic outcome and reduced side effects. As many diseased tissues are feathered with acidic characteristics microenvironment, pH-sensitive biomaterials for drug delivery present great promise for the purpose, which could protect the therapeutic payloads from metabolism and degradation during in vivo circulation and exhibit responsive release of the therapeutics triggered by the acidic pathological tissues, especially for cancer treatment. In the past decades, many methodologies, such as acidic cleavage linkage, have been applied for fabrication of pH-responsive materials for both in vitro and in vivo applications. In this review, we will summarize some pH-sensitive drug delivery system for medical application, mainly focusing on the pH-sensitive linkage bonds and pH-sensitive biomaterials.

Bone is a structurally complex and dynamic tissue that plays a crucial role in mobility and skeletal stability. However, conditions such as osteoporosis, osteoarthritis, trauma-induced fractures, infections, and malignancies often necessitate the use of orthopedic and dental implants. Despite significant progress in implant biomaterials, challenges such as bacterial infection, inflammation, and loosening continue to compromise implant longevity, frequently leading to revision surgeries and extended recovery times. Smart coatings have emerged as a next-generation solution to these problems by providing on-demand, localized therapeutic responses to microenvironmental changes around implants and promoting bone regeneration. Such coatings can minimize antibiotic resistance by enabling controlled, stimulus-triggered drug release. Although the idea of using pH-sensitivity as a tool to make smart coatings is not a new thought, there are no options currently good enough to enter clinical studies. This review provides a comprehensive overview of recent advances in pH-sensitive polymers, hybrid composites, porous architectures, and bioactive linkers designed to dynamically respond to pathological pH variations at implant sites. By investigating the mechanisms of action, antibacterial and anti-inflammatory effects, and roles in bone regeneration, it is shown that the ability to provide time-dependent drug release for both short-term and long-term infections, as well as keeping the environment welcoming to the bone cell growth and replacement, is not an easy goal to reach, even with a fully biocompatable, non-toxic, and semi-biodegradable (one that releases the drug, but does not fade away) coating material compound. Reviewing all available options, including their functions and failures, finally, emerging trends, translational barriers, and future opportunities for clinical implementation are highlighted, underscoring the transformative potential of bioresponsive coatings in orthopedic and dental implant technologies.

Hydrogels are superior wound dressings because they can provide protection and hydration of the wound, as well as the controlled release of therapeutic substances to aid tissue regeneration and the healing process. Hydrogels obtained from natural precursors are preferred because of their low cost, biocompatibility, and biodegradability. We describe the synthesis of novel functional hydrogels based on two natural products—citric acid (CA) and pentane-1,2,5-triol (PT, a product from lignocellulose processing) and poly(ethylene glycol) (PEG-600)—via an environment friendly approach. The hydrogels were prepared via monomer crosslinking through a polycondensation reaction at an elevated temperature in the absence of any solvent. The reagents were blended at three different compositions with molar ratios of hydroxyl (from PT and PEG) to carboxyl (from CA) groups of 1:1, 1:1.4, and 1.4:1, respectively. The effect of the composition on the physicomechanical properties of materials was investigated. All hydrogels exhibited pH-sensitive behavior, while the swelling degree and elastic modulus were dependent on the composition of the polymer network. The proteolytic enzyme serratiopeptidase (SER) was loaded into a hydrogel via physical absorption as a model drug. The release profile of SER and the effects of the enzyme on healthy skin cells were assessed. The results showed that the hydrogel carrier could provide the complete release of the loaded enzyme.

Polymer-grafted nanomaterials based on carbon allotropes and their derivatives (graphene oxide (GO), etc.) are typically prepared by successive reaction stages that depend upon the initial functionalities in the nanostructure and the polymerization type needed for grafting. However, due to the multiple variables involved in the functionalization steps, it is commonly difficult to predict the properties in the final product and to correlate the material history with its final performance. In this work, we explored the steps needed to graft the carboxylic acid moieties in GO (COOH@GO) with a pH-sensitive polymer, poly[2-(diethylamino)ethyl methacrylate] (poly[DEAEMA]), varying the reactant ratios at each stage prior to polymerization. We studied the combinatorial relationship between these variables and the behavior of the novel grafted material GO-g-poly[DEAEMA], in terms of swelling ratio vs. pH (%Q) in solid specimens and potentiometric response vs. Log[H+] in a solid-state sensor format. We first introduced N-hydroxysuccinimide (NHS)-ester moieties at the –COOH groups (GO-g-NHS) by a classical activation with N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide (EDC). Then, we substituted the NHS-ester groups by polymerizable amide-linked acrylic moieties using 2-aminoethyl methacrylate (AEMA) at different ratios to finally introduce the polymer chains via radical polymerization in an excess of DEAEMA monomer. We found correlated trends in swelling pH range, interval of maximum and minimum swelling values, response in potentiometry and potentiometric linear range vs. Log[H+] and could establish their relationship with the combinatorial stoichiometries in synthetic stages.

Intelligent materials for monitoring the condition of the packaged food or its surroundings are highly desired to ensure food safety. In this paper, UV-curable silicone-modified materials for monitoring the freshness of high-protein food such as shrimp and pork were prepared from polyurethane acrylates with covalent-grafted neutral red groups and thiol silicone resin. The UV-curable materials exhibited visible pH-sensitive performance and long-term color stability because their color did not change when they were immersed in aqueous solutions with different pH values for 20 min, and the color remained even when they were immersed for over 5 h. The distinctive color variation in the UV coatings makes them suitable as potential pH-sensitive sensors. These pH-sensitive intelligent materials can be applied to monitor the freshness of high-protein food such as shrimp and pork. Additionally, the thermal stability and adhesive properties of the UV-curable materials were also studied. A conclusion can be drawn that the covalent bonding of neutral red groups onto a silicone-modified polymer matrix is an ideal strategy for developing pH-sensitive intelligent materials with good pH stability for monitoring the freshness of high-protein food.

Surgical procedures trigger dynamic inflammatory responses that influence postoperative pain, wound healing, and long-term outcomes. Conventional therapies rely on the systemic delivery of anti-inflammatory and analgesic agents, which often lack spatiotemporal precision and carry significant side effects. Inflammation-responsive hydrogels offer a promising alternative by enabling localized, stimulus-adaptive drug release aligned with the evolving biochemical milieu of surgical wounds. These smart biomaterials respond to endogenous triggers, such as reactive oxygen species, acidic pH, and proteolytic enzymes, allowing precise modulation of inflammation and tissue repair. This narrative review outlines the pathophysiological features of perioperative inflammation and the design principles of responsive hydrogel systems, including pH-, reactive oxygen species-, enzyme-sensitive, and multi-stimuli platforms. We evaluated the integration of key payloads, NSAIDs, corticosteroids, α2-adrenergic agonists, and biologics, highlighting their therapeutic synergy and translational relevance. Preclinical studies across soft tissue, orthopedic, thoracic, and abdominal models have demonstrated the efficacy of these systems in modulating immune responses, reducing pain, and enhancing regeneration. Despite these encouraging results, challenges remain, including trigger fidelity, surgical compatibility, and regulatory readiness. Future advances in biosensor integration, logic-based design, and artificial intelligence-guided formulation may accelerate clinical translation. Inflammation-responsive hydrogels represent a transformative strategy for precise perioperative care.

The dual-emissive N, S co-doped carbon dots (N, S-CDs) with a long emission wavelength were synthesized via solvothermal method. The N, S-CDs possess relatively high photoluminescence (PL) quantum yield (QY) (35.7%) towards near-infrared fluorescent peak up to 648 nm. With the advanced characterization techniques including X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), etc. It is found that the doped N, S elements play an important role in the formation of high QY CDs. The N, S-CDs exist distinct pH-sensitive feature with reversible fluorescence in a good linear relationship with pH values in the range of 1.0–13.0. What is more, N, S-CDs can be used as an ultrasensitive Ag + probe sensor with the resolution up to 0.4 μM. This finding will expand the application of as prepared N, S-CDs in sensing and environmental fields.

During the last decade, pH-sensitive biomaterials containing antibacterial agents have grown exponentially in soft tissue engineering. The aim of this study is to synthesize a biodegradable pH sensitive and antibacterial hydrogel with adjustable mechanical and physical properties for soft tissue engineering. This biodegradable copolymer hydrogel was made of Poly-L-Arginine methacrylate (Poly-L-ArgMA) and different poly (β- amino ester) (PβAE) polymers. PβAE was prepared with four different diacrylate/diamine monomers including; 1.1:1 (PβAE1), 1.5:1 (PβAE1.5), 2:1 (PβAE2), and 3:1 (PβAE3), which was UV cross-linked using dimethoxy phenyl-acetophenone agent. These PβAE were then used for preparation of Poly-L-ArgMA/PβAE polymers and revealed a tunable swelling ratio, depending on the pH conditions. Noticeably, the swelling ratio increased by 1.5 times when the pH decreased from 7.4 to 5.6 in the Poly-L-ArgMA/PβAE1.5 sample. Also, the controllable degradation rate and different mechanical properties were obtained, depending on the PβAE monomer ratio. Noticeably, the tensile strength of the PβAE hydrogel increased from 0.10 ± 0.04 MPa to 2.42 ± 0.3 MPa, when the acrylate/diamine monomer molar ratio increased from 1.1:1 to 3:1. In addition, Poly-L-ArgMA/PβAE samples significantly improved L929 cell viability, attachment and proliferation. Poly-L-ArgMA also enhanced the antibacterial activities of PβAE against both Escherichia coli (~5.1 times) and Staphylococcus aureus (~2.7 times). In summary, the antibacterial and pH-sensitive Poly-L-ArgMA/PβAE1.5 with suitable mechanical, degradation and biological properties could be an appropriate candidate for soft tissue engineering, specifically wound healing applications.

As a chitin- and glucosamine-derived polysaccharide, chitosan is biodegradable, biocompatible, and non-toxic. Among the latest high-value engineering materials, chitosan hydrogels own outstanding features such as biodegradability, biocompatibility, non-toxicity, swelling reversibility, flexible adaption to external triggers, and the capability of drug loading. Recently, applying chitosan hydrogels to facilitate human biological processes like inflammation has become an interesting topic demonstrated by many publications about their potential in wound dressing, tissue engineering, and treatment of cancer, Parkinson’s disease, and gastric ulcer. This paper reviews the most recent procedures for synthesizing chitosan hydrogels as a smart anti-inflammatory drug delivery system. The characteristics of chitosan hydrogel, including pH sensitivity, temperature sensitivity, electric sensitivity, and magnetic strength, for flexible anti-inflammation, are all discussed to provide a comprehensive overview of anti-inflammatory chitosan hydrogel.

Improving the safety efficacy ratio of existing drugs is a current challenge to be addressed rather than the development of novel drugs which involve much expense and time. The efficacy of drugs is affected by a number of factors such as their low aqueous solubility, unequal absorption along the gastrointestinal (GI) tract, risk of degradation in the acidic milieu of the stomach, low permeation of the drugs in the upper GI tract, systematic side effects, etc. This review aims to enlighten readers on the role of pH sensitive hydrogels in drug delivery, their mechanism of action, swelling, and drug release as a function of pH change along the GI tract. The basis for the selection of materials, their structural features, physical and chemical properties, the presence of ionic pendant groups, and the influence of their pKa and pKb values on the ionization, consequent swelling, and targeted drug release are also highlighted.