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Hyaluronic acid (HA) is a biopolymer present in various human tissues, whose degradation causes tissue damage and diseases. The oxidized hyaluronic acid/adipic acid dihydrazide (oxi-HA/ADH) hydrogels have attracted attention due to their advantages such as thermosensitivity, injectability, in situ gelation, and sterilization. However, studies are still scarce in the literature as microcarriers. In that sense, this work is a study of oxi-HA/ADH microparticles of 215.6 ± 2.7 µm obtained by high-speed shearing (18,000 rpm at pH 7) as cell microcarriers. Results showed that BALB/c 3T3 fibroblasts and adipose mesenchymal stem cells (h-AdMSC) cultured on the oxi-HA/ADH microcarriers presented a higher growth of both cells in comparison with the hydrogel. Moreover, the extrusion force of oxi-HA/ADH microparticles was reduced by 35% and 55% with the addition of 25% and 75% HA fluid, respectively, thus improving its injectability. These results showed that oxi-HA/ADH microcarriers can be a potential injectable biopolymer for tissue regeneration applications.

Background and Objective : A previous study investigated the in vitro release of methylene blue (MB), a widely used cationic dye in biomedical applications, from nanocellulose/nanoporous silicon (NC/nPSi) composites under conditions simulating body fluids. The results showed that MB release rates varied significantly with the nPSi concentration in the composite, highlighting its potential for controlled drug delivery. To further analyze the relationship between diffusion dynamics and the MB concentration, this study developed a finite element (FE) method to solve Fick's equations governing the drug delivery system. Methods : Release profiles of MB from NC/nPSi composites with varying nPSi concentrations (0%, 0.1%, 0.5%, and 1.0%) were experimentally measured in triplicate using phosphate-buffered saline (PBS) at 37 °C, pH 7.4, and 100 rpm. Mathematical models incorporating linear and quadratic dependencies of the diffusion coefficient on the MB concentration were developed and tested using the FE method. Model parameters were refined by minimizing the error between simulated and experimental MB release profiles. Results : The proposed FE method closely matched experimental data, validating its accuracy and robustness in simulating the diffusion and release processes. Conclusions : This study emphasizes the significant impact of the nPSi concentration on enhancing release control and highlights the importance of material composition in designing drug delivery systems. The findings suggest that the FE method can be effectively applied to model other complex systems, paving the way for advancements in precision drug delivery and broader biomedical applications.

Medical implants are designed to replace missing parts or improve body functions and must be capable of providing structural support or therapeutic intervention for a medical condition. Advances in materials science have enabled the development of devices made from metals, polymers, bioceramics, and composites, each with its specific advantages and limitations. This review analyzes the incorporation of biopolymers, proteins, and other biomacromolecules into implants, focusing on their role in biological integration and therapeutic functions. It synthesizes advancements in surface modification, discusses biomacromolecules as carriers for controlled drug release, and explores the application of nanoceramics and composites to improve osseointegration and tissue regeneration. Biomacromolecule systems are capable of interacting with device components and therapeutic agents - such as growth factors (GFs), antibiotics, and nanoceramics - allowing control over substance release. Incorporating therapeutic agents into these systems enables localized treatments for tissue regeneration, osseointegration, post-surgery infection control, and disease and pre-existing conditions. The review highlights these materials' therapeutic advantages and customization opportunities, by covering mechanical and biological perspectives. Developing composites and hybrid drug delivery systems align with recent efforts in interdisciplinary personalized medicine and implant innovations. For instance, a trend was observed for integrating inorganic (especially nanoceramics, e.g., hydroxyapatite) and organic phases in composites for better implant interaction with biological tissues and faster recovery. This article supports understanding how integrating these materials can create more personalized, functional, durable, and biocompatible implant devices., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Calais, Garcia, de Moura Júnior, Soares, Lona, Beppu, Hernandez-Montelongo and Rocha Neto.)

Nanocellulose (NC) is a promising material for drug delivery due to its high surface area-to-volume ratio, biocompatibility, biodegradability, and versatility in various formats (nanoparticles, hydrogels, microspheres, membranes, and films). In this study, nanocellulose films were derived from "Bolaina blanca" ( Guazuma crinita ) and combined with nanoporous silicon microparticles (nPSi) in concentrations ranging from 0.1% to 1.0% ( w / v ), using polyvinyl alcohol (PVA) as a binding agent to create NC/nPSi composite films for drug delivery systems. The physicochemical properties of the samples were characterized using UV-Vis spectroscopy, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The mechanical properties and drug release capabilities were also evaluated using methylene blue (MB) as an antibacterial drug model. Antibacterial assays were conducted against S. aureus and E. coli bacteria. The results show that NC/nPSi composites with 1% nPSi increased the T 50% by 10 °C and enhanced mechanical properties, such as a 70% increase in the elastic modulus and a 372% increase in elongation, compared to NC films. Additionally, MB released from NC/nPSi composites effectively inhibited the growth of both bacteria. It was also observed that the diffusion coefficients were inversely proportional to the % nPSi. These findings suggest that this novel NC/nPSi-based material can serve as an effective controlled drug release system.

Breast cancer ranks among the most commonly diagnosed cancers worldwide and bears the highest mortality rate. As an integral component of cancer treatment, mastectomy entails the complete removal of the affected breast. Typically, breast reconstruction, involving the use of silicone implants (augmentation mammaplasty), is employed to address the aftermath of mastectomy. To mitigate postoperative risks associated with mammaplasty, such as capsular contracture or bacterial infections, the functionalization of breast implants with coatings of cyclodextrin polymers as drug delivery systems represents an excellent alternative. In this context, our work focuses on the application of a mathematical model for simulating drug release from breast implants coated with cyclodextrin polymers. The proposed model considers a unidirectional diffusion process following Fick's second law, which was solved using the orthogonal collocation method, a numerical technique employed to approximate solutions for ordinary and partial differential equations. We conducted simulations to obtain release profiles for three therapeutic molecules: pirfenidone, used for preventing capsular contracture; rose Bengal, an anticancer agent; and the antimicrobial peptide KR-12. Furthermore, we calculated the diffusion profiles of these drugs through the cyclodextrin polymers, determining parameters related to diffusivity, solute solid-liquid partition coefficients, and the Sherwood number. Finally, integrating these parameters in COMSOL multiphysics simulations, the unidirectional diffusion mathematical model was validated.

In this report, we have used the DFT + U + V approach, an extension of the DFT + U approach that takes into account both on-site and intersite interactions, to simulate structural, magnetic, and electronic properties together with the Fe and O K-edge XAS spectra of Fe 3 O 4 above the Verwey temperature ( T v ). Moreover, we compared the simulated XAS spectra with experimental XAS data. We examined both orthogonalized and nonorthogonalized atomic orbital projectors and compared DFT + U + V to DFT, DFT + U , and HSE as a hybrid functional. It is noteworthy that, despite the widespread use of the same Hubbard U value for Fe oct and Fe tet at the DFT + U level in the literature, the HP code identified two distinct values for them using the Hubbard approaches (DFT + U and DFT + U + V ). The resulting Hubbard U and V parameters are strongly dependent on the chosen orbital projectors. This study demonstrates how DFT + U + V can improve the structural, magnetic, and electronic properties of Fe 3 O 4 compared to approximate DFT and DFT + U . In this context, DFT + U + V supports the half-metallic character of the bulk crystal Fe 3 O 4 above T v , since the Fermi level is found in the t 2g band with a Fe oct down-spin. Thus, the observations in the current study emphasize the significance of intersite interactions in the theoretical analysis of Fe 3 O 4 above the T v .

Mammaplasty is a widely performed surgical procedure worldwide, utilized for breast reconstruction, in the context of breast cancer treatment, and aesthetic purposes. To enhance post-operative outcomes and reduce risks (hematoma with required evacuation, capsular contracture, implant-associated infection and others), the controlled release of medicaments can be achieved using drug delivery systems based on cyclodextrins (CDs). In this study, our objective was to functionalize commercially available silicone breast implants with smooth and textured surfaces through in-situ polymerization of two CDs: β-CD/citric acid and 2-hydroxypropyl-β-CD/citric acid. This functionalization serves as a local drug delivery system for the controlled release of therapeutic molecules that potentially can be a preventive treatment for post-operative complications in mammaplasty interventions. Initially, we evaluated the pre-treatment of sample surfaces with O 2 plasma, followed by chitosan grafting. Subsequently, in-situ polymerization using both types of CDs was performed on implants. The results demonstrated that the proposed pre-treatment significantly increased the polymerization yield. The functionalized samples were characterized using microscopic and physicochemical techniques. To evaluate the efficacy of the proposed system for controlled drug delivery in augmentation mammaplasty, three different molecules were utilized: pirfenidone (PFD) for capsular contracture prevention, Rose Bengal (RB) as anticancer agent, and KR-12 peptide (KR-12) to prevent bacterial infection. The release kinetics of PFD, RB, and KR-12 were analyzed using the Korsmeyer-Peppas and monolithic solution mathematical models to identify the respective delivery mechanisms. The antibacterial effect of KR-12 was assessed against Staphylococcus epidermidis and Pseudomonas aeruginosa , revealing that the antibacterial rate of functionalized samples loaded with KR-12 was dependent on the diffusion coefficients. Finally, due to the immunomodulatory properties of KR-12 peptide on epithelial cells, this type of cells was employed to investigate the cytotoxicity of the functionalized samples. These assays confirmed the superior properties of functionalized samples compared to unprotected implants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Escobar, Carrera, Naveas, Pulido, Manso, Guarnieri, Lancellotti, Cotta, Corrales-Ureña, Rischka and Hernandez-Montelongo.)

In the early 2000s, a method for cross-linking cyclodextrins (CDs) with citric acid (CTR) was developed. This method was nontoxic, environmentally friendly, and inexpensive compared to the others previously proposed in the literature. Since then, the CD/CTR biopolymers have been widely used as a coating on implants and other materials for biomedical applications. The present review aims to cover the chemical properties of CDs, the synthesis routes of CD/CTR, and their applications as drug-delivery systems when coated on different substrates. Likewise, the molecules released and other pharmaceutical aspects involved are addressed. Moreover, the different methods of pretreatment applied on the substrates before the in situ polymerization of CD/CTR are also reviewed as a key element in the final functionality. This process is not trivial because it depends on the surface chemistry, geometry, and physical properties of the material to be coated. The biocompatibility of the polymer was also highlighted. Finally, the mechanisms of release generated in the CD/CTR coatings were analyzed, including the mathematical model of Korsmeyer-Peppas, which has been dominantly used to explain the release kinetics of drug-delivery systems based on these biopolymers. The flexibility of CD/CTR to host a wide variety of drugs, of the in situ polymerization to integrate with diverse implantable materials, and the controllable release kinetics provide a set of advantages, thereby ensuring a wide range of future uses.

This work focuses on the mathematical analysis of the controlled release of a standardized extract of A. chica from chitosan/alginate (C/A) membranes, which can be used for the treatment of skin lesions. Four different types of C/A membranes were tested: a dense membrane (CA), a dense and flexible membrane (CAS), a porous membrane (CAP) and a porous and flexible membrane (CAPS). The Arrabidae chica extract release profiles were obtained experimentally in vitro using PBS at 37 °C and pH 7. Experimental data of release kinetics were analyzed using five classical models from the literature: Zero Order, First Order, Higuchi, Korsmeyer-Peppas and Weibull functions. Results for the Korsmeyer-Peppas model showed that the release of A. chica extract from four membrane formulations was by a diffusion through a partially swollen matrix and through a water filled network mesh; however, the Weibull model suggested that non-porous membranes (CA and CAS) had fractal geometry and that porous membranes (CAP and CAPS) have highly disorganized structures. Nevertheless, by applying an explicit optimization method that employs a cost function to determine the model parameters that best fit to experimental data, the results indicated that the Weibull model showed the best simulation for the release profiles from the four membranes: CA, CAS and CAP presented Fickian diffusion through a polymeric matrix of fractal geometry, and only the CAPS membrane showed a highly disordered matrix. The use of this cost function optimization had the significant advantage of higher fitting sensitivity.

Microchannels can be used to simulate xylem vessels and investigate phytopathogen colonization under controlled conditions. In this work, we explore surface functionalization strategies for polydimethylsiloxane and glass microchannels to study microenvironment colonization by Xylella fastidiosa subsp. pauca cells. We closely monitored cell initial adhesion, growth, and motility inside microfluidic channels as a function of chemical environments that mimic those found in xylem vessels. Carboxymethylcellulose (CMC), a synthetic cellulose, and an adhesin that is overexpressed during early stages of X. fastidiosa biofilm formation, XadA1 protein, were immobilized on the device's internal surfaces. This latter protocol increased bacterial density as compared with CMC. We quantitatively evaluated the different X. fastidiosa attachment affinities to each type of microchannel surface using a mathematical model and experimental observations acquired under constant flow of culture medium. We thus estimate that bacterial cells present ∼4 and 82% better adhesion rates in CMC- and XadA1-functionalized channels, respectively. Furthermore, variable flow experiments show that bacterial adhesion forces against shear stresses approximately doubled in value for the XadA1-functionalized microchannel as compared with the polydimethylsiloxane and glass pristine channels. These results show the viability of functionalized microchannels to mimic xylem vessels and corroborate the important role of chemical environments, and particularly XadA1 adhesin, for early stages of X. fastidiosa biofilm formation, as well as adhesivity modulation along the pathogen life cycle., (Copyright © 2021 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

c-di-GMP is a major player in the switch between biofilm and motile lifestyles. Several bacteria exhibit a large number of c-di-GMP metabolizing proteins, thus a fine-tuning of this nucleotide levels may occur. It is hypothesized that some c-di-GMP metabolizing proteins would provide the global c-di-GMP levels inside the cell whereas others would maintain a localized pool, with the resulting c-di-GMP acting at the vicinity of its production. Although attractive, this hypothesis has yet to be demonstrated in Pseudomonas aeruginosa. We found that the diguanylate cyclase DgcP interacts with the cytosolic region of FimV, a polar peptidoglycan-binding protein involved in type IV pilus assembly. Moreover, DgcP is located at the cell poles in wild type cells but scattered in the cytoplasm of cells lacking FimV. Overexpression of dgcP leads to the classical phenotypes of high c-di-GMP levels (increased biofilm and impaired motilities) in the wild-type strain, but not in a ΔfimV background. Therefore, our findings suggest that DgcP activity is regulated by FimV. The polar localization of DgcP might contribute to a local c-di-GMP pool that can be sensed by other proteins at the cell pole, bringing to light a specialized function for a specific diguanylate cyclase.

Silk fibroin (SF) and konjac glucomannan (KGM) are promising materials in the biomedical field due to their low toxicity, biocompatibility, biodegradability and low immune response. Beads of these natural polymers are interesting scaffolds for biomedical applications, but their fabrication is a challenge due to their low stability and the necessary adaptation of their chemical and mechanical properties to be successfully applied. In that sense, this study aimed to synthesize a blend of silk fibroin and konjac glucomannan (SF/KGM) in the form of porous beads obtained through dripping into liquid nitrogen, with a post-treatment using ethanol. Intermolecular hydrogen bonds promoted the integration of SF and KGM. Treated beads showed higher porous size, crystallinity, and stability than untreated beads. Characterization analyses by Fourier-transform infrared spectroscopy (FTIR), thermogravimetric (TGA), and X-ray diffraction (XDR) evidenced that ethanol treatment allows a conformational transition from silk I to silk II in SF and an increase in the KGM deacetylation. Those chemical changes significantly enhanced the mechanical resistance of SF/KGM beads in comparison to pure SF and KGM beads. Moreover, samples showed cytocompatibility with HaCaT and BALB/c 3T3 cells.

Nanostructured porous silicon (PSi) elicits as a very attractive material for future biosensing systems due to its high surface area, biocompatibility and well-established fabrication methods. In order to engineer its performance as a biosensor transducer platform, the density of immunoglobulins properly immobilized and oriented onto the surface needs to be optimized. In this work we fabricated and characterized a novel biosensing system focusing on the improvement of the biofunctionalization cascade. The system consists on a chemically oxidized PSi platform derivatized with 3-aminopropyltriethoxysilane (APTS) that is coupled to Staphylococcus protein A (SpA). The chemical oxidation has previously demonstrated to enhance the biofunctionalization process and here "by implementing SpA" a molecularly oriented immunosensor is achieved. The biosensor system is characterized in terms of its chemical composition, wettability and optical reflectance. Finally, this system is successfully exploited to develop a biosensor for detecting asymmetric dimethylarginine (ADMA), an endogenous molecule involved in cardiovascular diseases. Therefore, this work is relevant from the point of view of design and optimization of the biomolecular immobilization cascade on PSi surfaces with the added value of contribution to the development of new assays for detecting ADMA with a view on prevention of cardiovascular diseases., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Porous silicon (PSi) is widely used in biological experiments, owing to its biocompatibility and well-established fabrication methods that allow tailoring its surface. Nevertheless, there are some unresolved issues such as deciding whether the stabilization of PSi is necessary for its biological applications and evaluating the effects of PSi stabilization on the surface biofunctionalization with proteins. In this work we demonstrate that non-stabilized PSi is prone to detachment owing to the stress induced upon biomolecular adsorption. Biofunctionalized non-stabilized PSi loses the interference properties characteristic of a thin film, and groove-like structures resulting from a final layer collapse were observed by scanning electron microscopy. Likewise, direct PSi derivatization with 3-aminopropyl-triethoxysilane (APTS) does not stabilize PSi against immunoglobulin biofunctionalization. To overcome this problem, we developed a simple chemical process of stabilizing PSi (CoxPSi) for biological applications, which has several advantages over thermal stabilization (ToxPSi). The process consists of chemical oxidation in H 2 O 2 , surface derivatization with APTS and a curing step at 120 °C. This process offers integral homogeneous PSi morphology, hydrophilic surface termination (contact angle θ = 26°) and highly efficient derivatized and biofunctionalized PSi surfaces (six times more efficient than ToxPSi). All these features are highly desirable for biological applications, such as biosensing, where our results can be used for the design and optimization of the biomolecular immobilization cascade on PSi surfaces.