Release Of Bioactive Molecules Research Articles

Sweet but Challenging: Tackling the Complexity of GAGs with Engineered Tailor-Made Biomaterials.

Glycosaminoglycans (GAGs) play a crucial role in tissue homeostasis by regulating the activity and diffusion of bioactive molecules. Incorporating GAGs into biomaterials has emerged as a widely adopted strategy in medical applications, owing to their biocompatibility and ability to control the release of bioactive molecules. Nevertheless, immobilized GAGs on biomaterials can elicit distinct cellular responses compared to their soluble forms, underscoring the need to understand the interactions between GAG and bioactive molecules within engineered functional biomaterials. By controlling critical parameters such as GAG type, density, and sulfation, it becomes possible to precisely delineate GAG functions within a biomaterial context and to better mimic specific tissue properties, enabling tailored design of GAG-based biomaterials for specific medical applications. However, this requires access to pure and well-characterized GAG compounds, which remains challenging. This review focuses on different strategies for producing well-defined GAGs and explores high-throughput approaches employed to investigate GAG-growth factor interactions and to quantify cellular responses on GAG-based biomaterials. These automated methods hold considerable promise for improving the understanding of the diverse functions of GAGs. In perspective, the scientific community is encouraged to adopt a rational approach in designing GAG-based biomaterials, taking into account the in vivo properties of the targeted tissue for medical applications.

Enhanced osteogenicity of the demineralized bone-dermal matrix composite by the optimal partial demineralization for sustained release of bioactive molecules.

Allogenic demineralized bone matrix (DBM), processed to expose bioactive proteins imbedded by calcium salts, is widely used for bone repair and regeneration as an alternative to the autologous bone graft. However, demineralized bone matrices from tissue banks vary significantly in residual calcium content and osteogenicity for clinical bone regeneration. The present study produced DBM with various residual calcium contents by partial demineralization using ethylenediaminetetraacetic acid disodium (EDTA) and hydrochloric acid. Compositional analysis reveals that, as the percent weight loss of bone materials increases from 0% to 74.9% during demineralization, the residual calcium content of DBM decreases from 24.8% to 0.2% and collagen content increases from 29.7% to 92.6%. Calorimetrical analysis and Fourier transform infrared (FTIR) analysis demonstrated that demineralization to the residual calcium content of <4% enables the complete exposure and/or release of bone collagen fibers and other bioactive molecules. In order to evaluate the relationship between the extent of demineralization and the osteogenicity of DBM, DBM particles were fabricated with the aid of acellular dermal matrix (ADM) microfibers to form flexible foam-like DBM/ADM composites. Proteomic analysis identified various type collagens and bone formation-related bioactive molecules in both ADM and DBM. Using the rat bilateral Φ = 5 mm calvarium defect repair model, the study had shown that the DBM/ADM composite with ~20% DBM residual calcium (e.g., ~40% calcium being removed) maximized the osteogenicity for bone defect repair after 4 and 8 weeks. DBM with ~40% calcium removal had the maximal osteogenicity presumably through the sustained release of bioactive molecules during the process of bone regeneration.

Injectable Microparticle-containing hydrogel with controlled release of bioactive molecules for facial rejuvenation

The skin is the largest organ and a crucial barrier for protection against various intrinsic and extrinsic factors. As we age, the skin's components become more vulnerable to damage, forming wrinkles. Among different procedures, hyaluronic acid-based hydrogel has been extensively utilized for skin regeneration and reducing wrinkles. However, it has limitations like low retention and weak mechanical properties. In this study, we suggested the poly(l-lactic acid) (PLLA) microparticles containing alkaline magnesium hydroxide and nitric oxide-generating zinc oxide and rejuvenative hyaluronic acid (HA) hydrogels including these functional microparticles and asiaticoside, creating a novel delivery system for skin rejuvenation and regeneration. The fabricated rejuvenative hydrogels have exhibited enhanced biocompatibility, pH neutralization, reactive oxygen species scavenging, collagen biosynthesis, and angiogenesis capabilities in vitro and in vivo. Additionally, an excellent volume retention ability was demonstrated due to the numerous hydrogen bonds that formed between hyaluronic acid and asiaticoside. Overall, our advanced injectable hydrogel containing functional microparticles, with controlled release of bioactive molecules, has a significant potential for enhancing the regeneration and rejuvenation of the skin.

A guanosine/konjac glucomannan supramolecular hydrogel with antioxidant, antibacterial and immunoregulatory properties for cutaneous wound treatment

Developing naturally-derived wound dressing materials with intrinsic therapeutic effects is desirable for the clinical applications. Recently, guanosine-based supramolecular G-quadruplex (G4) hydrogel exhibited great potential in preparing biological materials due to its simple fabrication method and responsive gel networks. However, the weak mechanical properties and the consequent burst release of bioactive molecules restrict its clinical applications. Herein, we found that konjac glucomannan (KGM) with immunoregulatory effect did not affect the self-assembly of G-quadruplexes and thus effectively enhancing the mechanical properties of G4 hydrogel. Aloin, as a model drug, was in situ loaded into gel networks, finally obtaining the G4/Aloin-KGM hydrogel. This hydrogel exhibited porous morphology, swelling ability and hemostatic capability. Boronate bonds in G4 networks and aloin collectively endowed the hydrogel with excellent antioxidant performance. Meanwhile, aloin also provided outstanding in vitro and in vivo bactericidal ability. The wounds treated with this biocompatible hydrogel demonstrated faster regeneration of epithelial and dermal tissues, and the whole wound healing stages were accelerated by promoting collagen deposition, facilitating macrophage polarization towards M2 phenotype, down-regulating the expression level of IL-6, and up-regulating the expression level of IL-10, CD31 and α-SMA.

A Commercial Clay-Based Material as a Carrier for Targeted Lysozyme Delivery in Animal Feed.

The controlled supply of bioactive molecules is a subject of debate in animal nutrition. The release of bioactive molecules in the target organ, in this case the intestine, results in improved feed, as well as having a lower environmental impact. However, the degradation of bioactive molecules' in transit in the gastrointestinal passage is still an unresolved issue. This paper discusses the feasibility of a simple and cost-effective procedure to bypass the degradation problem. A solid/liquid adsorption procedure was applied, and the operating parameters (pH, reaction time, and LY initial concentration) were studied. Lysozyme is used in this work as a representative bioactive molecule, while Adsorbo®, a commercial mixture of clay minerals and zeolites which meets current feed regulations, is used as the carrier. A maximum LY loading of 32 mgLY/gAD (LY(32)-AD) was obtained, with fixing pH in the range 7.5-8, initial LY content at 37.5 mgLY/gAD, and reaction time at 30 min. A full characterisation of the hybrid organoclay highlighted that LY molecules were homogeneously spread on the carrier's surface, where the LY-carrier interaction was mainly due to charge interaction. Preliminary release tests performed on the LY(32)-AD synthesised sample showed a higher releasing capacity, raising the pH from 3 to 7. In addition, a preliminary Trolox equivalent antioxidant capacity (TEAC) assay showed an antioxidant capacity for the LY of 1.47 ± 0.18 µmol TroloxEq/g with an inhibition percentage of 33.20 ± 3.94%.

Near Infrared Light‐Triggered Photocatalytic Decaging for Remote‐Controlled Spatiotemporal Activation in Living Mice**

AbstractSpatiotemporal manipulation of biological processes in living animals using noninvasive, remote‐controlled stimuli is a captivating but challenging endeavor. Herein, we present the development of a biocompatible photocatalytic technology termed CAT‐NIR, which uses external near infrared light (NIR, 740 nm) to trigger decaging reactions in living mice. The Os(II) terpyridine complex was identified as an efficient NIR photocatalyst for promoting deboronative hydroxylation reactions via superoxide generation in the presence of NIR light, resulting in the deprotection of phenol groups and the release of bioactive molecules under living conditions. The validation of the CAT‐NIR system was demonstrated through the NIR‐triggered rescue of fluorophores, prodrugs as well as biomolecules ranging from amino acids, peptides to proteins. Furthermore, by combining genetic code expansion and computer‐aided screening, CAT‐NIR could regulate affibody binding to the cell surface receptor HER2, providing a selective cell tagging technology through external NIR light. In particular, the tissue‐penetrating ability of NIR light allowed for facile prodrug activation in living mice, enabling noninvasive, remote‐controlled rescue of drug molecules. Given its broad adaptability, this CAT‐NIR system may open new opportunities for manipulating the functions of bioactive molecules in living animals using external NIR light with spatiotemporal resolution.

Near Infrared Light-Triggered Photocatalytic Decaging for Remote-Controlled Spatiotemporal Activation in Living Mice.

Spatiotemporal manipulation of biological processes in living animals using noninvasive, remote-controlled stimuli is a captivating but challenging endeavor. Herein, we present the development of a biocompatible photocatalytic technology termed CAT-NIR, which uses external near infrared light (NIR, 740 nm) to trigger decaging reactions in living mice. The Os(II) terpyridine complex was identified as an efficient NIR photocatalyst for promoting deboronative hydroxylation reactions via superoxide generation in the presence of NIR light, resulting in the deprotection of phenol groups and the release of bioactive molecules under living conditions. The validation of the CAT-NIR system was demonstrated through the NIR-triggered rescue of fluorophores, prodrugs as well as biomolecules ranging from amino acids, peptides to proteins. Furthermore, by combining genetic code expansion and computer-aided screening, CAT-NIR could regulate affibody binding to the cell surface receptor HER2, providing a selective cell tagging technology through external NIR light. In particular, the tissue-penetrating ability of NIR light allowed for facile prodrug activation in living mice, enabling noninvasive, remote-controlled rescue of drug molecules. Given its broad adaptability, this CAT-NIR system may open new opportunities for manipulating the functions of bioactive molecules in living animals using external NIR light with spatiotemporal resolution.

Acid···Amide Supramolecular Synthon for Tuning Amino Acid-Based Hydrogels' Properties.

Supramolecular hydrogels formed by the self-assembly of N-Fmoc-L-phenylalanine derivatives are gaining relevance for several applications in the materials and biomedical fields. In the challenging attempt to predict or tune their properties, we selected Fmoc-pentafluorophenylalanine (1) as a model efficient gelator, and studied its self-assembly in the presence of benzamide (2), a non-gelator able to form strong hydrogen bonding with the amino acid carboxylic group. Equimolar mixtures of 1 and 2 in organic solvents afforded a 1:1 co-crystal thanks to the formation of an acid···amide heterodimeric supramolecular synthon. The same synthon occurred in the transparent gels formed by mixing the two components in 1:1 ratio in aqueous media, as revealed by structural, spectroscopic, and thermal characterizations performed on both the co-crystal powder and the lyophilized hydrogel. These findings revealed the possibility to modulate the properties of amino acid-based hydrogels, by involving the gelator in the formation of a co-crystal. Such crystal engineering-based approach is demonstrated to be also useful for the time-delayed release of suitable bioactive molecules, when involved as hydrogel coformers.

Chitosan Resin-Modified Glass Ionomer Cement Containing Epidermal Growth Factor Promotes Pulp Cell Proliferation with a Minimum Effect on Fluoride and Aluminum Release.

The development of biomaterials that are able to control the release of bioactive molecules is a challenging task for regenerative dentistry. This study aimed to enhance resin-modified glass ionomer cement (RMGIC) for the release of epidermal growth factor (EGF). This RMGIC was formulated from RMGIC powder supplemented with 15% (w/w) chitosan at a molecular weight of either 62 or 545 kDa with 5% bovine serum albumin mixed with the same liquid component as the Vitrebond. EGF was added while mixing. ELISA was used to determine EGF release from the specimen immersed in phosphate-buffered saline at 1 h, 3 h, 24 h, 3 d, 1 wk, 2 wks, and 3 wks. Fluoride and aluminum release at 1, 3, 5, and 7 d was measured by electrode and inductively coupled plasma optical emission spectrometry. Pulp cell viability was examined through MTT assays and the counting of cell numbers using a Coulter counter. The RMGIC with 65 kDa chitosan is able to prolong the release of EGF for significantly longer than RMGIC for at least 3 wks due to its retained bioactivity in promoting pulp cell proliferation. This modified RMGIC can prolong the release of fluoride, with a small amount of aluminum also released for a limited time. This biomaterial could be useful in regenerating pulp-dentin complexes.

Magnetic-Responsive Liposomal Hydrogel Membranes for Controlled Release of Small Bioactive Molecules-An Insight into the Release Kinetics.

This work explores the unique features of magnetic-responsive hydrogels to obtain liposomal hydrogel delivery platforms capable of precise magnetically modulated drug release based on the mechanical responses of these hydrogels when exposed to an external magnetic field. Magnetic-responsive liposomal hydrogel delivery systems were prepared by encapsulation of 1,2-dipalmitoyl-sn-glycero-3-phosphocoline (DPPC) multilayered vesicles (MLVs) loaded with ferulic acid (FA), i.e., DPPC:FA liposomes, into gelatin hydrogel membranes containing dispersed iron oxide nanoparticles (MNPs), i.e., magnetic-responsive gelatin. The FA release mechanisms and kinetics from magnetic-responsive liposomal gelatin were studied and compared with those obtained with conventional drug delivery systems, e.g., free liposomal suspensions and hydrogel matrices, to access the effect of liposome entrapment and magnetic field on FA delivery. FA release from liposomal gelatin membranes was well described by the Korsmeyer-Peppas model, indicating that FA release occurred under a controlled diffusional regime, with or without magnetic stimulation. DPPC:FA liposomal gelatin systems provided smoother controlled FA release, relative to that obtained with the liposome suspensions and with the hydrogel platforms, suggesting the promising application of liposomal hydrogel systems in longer-term therapeutics. The magnetic field, with low intensity (0.08 T), was found to stimulate the FA release from magnetic-responsive liposomal gelatin systems, increasing the release rates while shifting the FA release to a quasi-Fickian mechanism. The magnetic-responsive liposomal hydrogels developed in this work offer the possibility to magnetically activate drug release from these liposomal platforms based on a non-thermal related delivery strategy, paving the way for the development of novel and more efficient applications of MLVs and liposomal delivery systems in biomedicine.

Innovative Nanostructured Fillers for Dental Resins: Nanoporous Alumina and Titania Nanotubes.

The possibility of improving dental restorative materials is investigated through the addition of two different types of fillers to a polymeric resin. These fillers, consisting of porous alumina and TiO2 nanotubes, are compared based on their common physicochemical properties on the nanometric scale. The aim was to characterize and compare the surface morphological properties of composite resins with different types of fillers using analytical techniques. Moreover, ways to optimize the mechanical, surface, and aesthetic properties of reinforced polymer composites are discussed for applications in dental treatments. Filler-reinforced polymer composites are the most widely used materials in curing dental pathologies, although it remains necessary to optimize properties such as mechanical resistance, surface characteristics, and biocompatibility. Anodized porous alumina nanoparticles prepared by electrochemical anodization offer a route to improve mechanical properties and biocompatibility as well as to allow for the controlled release of bioactive molecules that can promote tissue integration and regeneration. The inclusion of TiO2 nanotubes prepared by hydrothermal treatment in the resin matrix promotes the improvement of mechanical and physical properties such as strength, stiffness, and hardness, as well as aesthetic properties such as color stability and translucency. The surface morphological properties of composite resins with anodized porous alumina and TiO2 nanotube fillers were characterized by Atomic Force Microscopy (AFM), Scanning Electron Microscopy (SEM), and X-ray chemical analysis. In addition, the stress-strain behavior of the two composite resins is examined in comparison with enamel and dentin.

Abstract 2502: The role of high mobility group box-1 protein (HMGB1) in the microenvironment of non-small cell lung cancer

Abstract Introduction: The tumor microenvironment (TME) is critical in determining tumor development and progression. Among stromal cells in TME, cancer associated fibroblasts (CAFs) play a central role and are involved in various signals through their interaction with cancer cells in most solid tumors, leading to cancer progression and acquisition of drug resistance. Under these TME conditions, tumor cell death such as necrosis occurs, which in turn, results in the ectopic release of bioactive molecules collectively termed as damage-associated molecular patterns (DAMPs), which has been reported to play an important role in cancer progression. The purpose of this study is to clarify the effects of cancer cell-derived HMGB1, a representative DAMPs, on CAFs and to investigate whether it could be a potential therapeutic target. Methods: We established CAFs from resected non-small cell lung cancer (NSCLC) specimens and investigated the biological activity of HMGB1 on CAFs using in vitro co-culture models with NSCLC cell lines. Furthermore, we assessed the therapeutic efficacy of targeting cancer cell-derived HMGB1 using anti-HMGB1 neutralizing antibody. Results: Intracellular HMGB1 was expressed more in NSCLC cells than in normal bronchial epithelial cells and CAFs, and released from cancer cells extracellularly upon treatment with anticancer drugs. The stimulation with recombinant HMGB1 promoted the proliferation of CAFs in a dose-dependent manner, but not lung cancer cells. Co-culture with CAFs promoted cancer cells’ migratory ability and drug resistance, and stimulation with recombinant HMGB1 further enhanced these promoting effects, while administration of anti-HMGB1 neutralizing antibody suppressed these effects. On the other hand, these inhibitory effects were not observed in the absence of CAFs, suggestingHMGB1 has effect on CAFs, but not direct on cancer cells. Conclusion: HMGB1 plays an important role in cancer progression and acquisition of therapeutic resistance by upregulating the CAFs’ proliferation and activity and could be a therapeutic target in NSCLC. Citation Format: Tomohiro Habu, Keiichi Date, Ken Suzawa, Mao Yoshikawa, Masayoshi Ohki, Kazuma Iwata, Naoki Matsuda, Yin Min Thu, Kazuhiko Shien, Hiromasa Yamamoto, Shinichi Toyooka. The role of high mobility group box-1 protein (HMGB1) in the microenvironment of non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2502.

ESIPT-, AIE-, and AIE + ESIPT-Based Light-Activated Drug Delivery Systems and Bioactive Donors for Targeted Disease Treatment

Targeted release of bioactive molecules for therapeutic purposes is a key area in the biomedical field that is growing quickly, where bioactive molecules are released passively or actively from drug delivery systems (DDSs) or bioactive donors. In the past decade, researchers have identified light as one of the prime stimuli that can implement the efficient spatiotemporally targeted delivery of drugs or gaseous molecules with minimal cytotoxicity and a real-time monitoring ability. This perspective emphasizes recent advances in the photophysical properties of ESIPT- (excited-state intramolecular proton transfer), AIE- (aggregation-induced emission), and AIE + ESIPT-attributed light-activated delivery systems or donors. The three major sections of this perspective describe the distinctive features of DDSs and donors concerning their design, synthesis, photophysical and photochemical properties, and in vitro and in vivo studies demonstrating their relevance as carrier molecules for releasing cancer drugs and gaseous molecules in the biological system.

A Computational Model for the Release of Bioactive Molecules by the Hydrolytic Degradation of a Functionalized Polyester-Based Scaffold.

This work presents a computational model to study the degradation behavior of polyester-based three-dimensional (3D) functionalized scaffolds for bone regeneration. As a case study, we investigated the behavior of a 3D-printed scaffold presenting a functionalized surface with ICOS-Fc, a bioactive protein able to stimulate bone regeneration and healing, inhibiting osteoclast activity. The aim of the model was to optimize the scaffold design to control its degradation and thus the release of grafted protein over time and space. Two different scenarios were considered: (i) a scaffold without macroporosity presenting a functionalized external surface; and (ii) a scaffold presenting an internal functionalized macroporous architecture with open channels to locally deliver the degradation products.

Development and characterization of Factor Xa-responsive materials for applications in cell culture and biologics delivery.

Stimuli-responsive biomaterials may be used to better control the release of bioactive molecules or cells for applications involving drug delivery and controlled cell release. In this study, we developed a Factor Xa (FXa)-responsive biomaterial capable of controlled release of pharmaceutical agents and cells from in vitro culture. FXa-cleavable substrates were formed as hydrogels that degraded in response to FXa enzyme over several hours. Hydrogels were shown to release both heparin and a model protein in response to FXa. Additionally, RGD-functionalized FXa-degradable hydrogels were used to culture mesenchymal stromal cells (MSCs), enabling FXa-mediated cell dissociation from hydrogels in a manner that preserved multicellular structures. Harvesting MSCs using FXa-mediated dissociation did not influence their differentiation capacity or indoleamine 2,3-dioxygenase (IDO) activity (a measure of immunomodulatory capacity). In all, this FXa-degradable hydrogel is a novel responsive biomaterial system that may be used for on-demand drug delivery, as well as for improving processes for in vitro culture of therapeutic cells.

Biopolymeric Coatings for Local Release of Therapeutics from Biomedical Implants.

The deployment of structures that enable localized release of bioactive molecules can result in more efficacious treatment of disease and better integration of implantable bionic devices. The strategic design of a biopolymeric coating can be used to engineer the optimal release profile depending on the task at hand. As illustrative examples, here advances in delivery of drugs from bone, brain, ocular, and cardiovascular implants are reviewed. These areas are focused to highlight that both hard and soft tissue implants can benefit from controlled localized delivery. The composition of biopolymers used to achieve appropriate delivery to the selected tissue types, and their corresponding outcomes are brought to the fore. To conclude, key factors in designing drug-loaded biopolymeric coatings for biomedical implants are highlighted.

Diverse nanocomposites as a potential dressing for diabetic wound healing.

Wound healing is a programmed process of continuous events which is impaired in the case of diabetic patients. This impaired process of healing in diabetics leads to amputation, longer hospitalisation, immobilisation, low self-esteem, and mortality in some patients. This problem has paved the way for several innovative strategies like the use of nanotechnology for the treatment of wounds in diabetic patients. The use of biomaterials, nanomaterials have advanced approaches in tissue engineering by designing multi-functional nanocomposite scaffolds. Stimuli-responsive scaffolds that interact with the wound microenvironment and controlled release of bioactive molecules have helped in overcoming barriers in healing. The use of different types of nanocomposite scaffolds for faster healing of diabetic wounds is constantly being studied. Nanocomposites have helped in addressing specific issues with respect to healing and improving angiogenesis. Method: A literature search was followed to retrieve the articles on strategies for wound healing in diabetes across several databases like PubMed, EMBASE, Scopus and Cochrane database. The search was performed in May 2022 by two researchers independently. They keywords used were "diabetic wounds, nanotechnology, nanocomposites, nanoparticles, chronic diabetic wounds, diabetic foot ulcer, hydrogel". Exclusion criteria included insulin resistance, burn wound, dressing material.

Release of Bioactive Molecules from Graphene Oxide-Alginate Hybrid Hydrogels: Effect of Crosslinking Method

To investigate the influence of crosslinking methods on the releasing performance of hybrid hydrogels, we synthesized two systems consisting of Graphene oxide (GO) as a functional element and alginate as polymer counterpart by means of ionic gelation (physical method, HA−GOP) and radical polymerization (chemical method, HA−GOC). Formulations were optimized to maximize the GO content (2.0 and 1.15% for HA−GOP and HA−GOC, respectively) and Curcumin (CUR) was loaded as a model drug at 2.5, 5.0, and 7.5% (by weight). The physico-chemical characterization confirmed the homogeneous incorporation of GO within the polymer network and the enhanced thermal stability of hybrid vs. blank hydrogels. The determination of swelling profiles showed a higher swelling degree for HA−GOC and a marked pH responsivity due to the COOH functionalities. Moreover, the application of external voltages modified the water affinity of HA−GOC, while they accelerated the degradation of HA−GOP due to the disruption of the crosslinking points and the partial dissolution of alginate. The evaluation of release profiles, extensively analysed by the application of semi-empirical mathematical models, showed a sustained release from hybrid hydrogels, and the possibility to modulate the releasing amount and rate by electro-stimulation of HA−GOC.

Development of a photosynthetic hydrogel as potential wound dressing for the local delivery of oxygen and bioactive molecules.

The development of biomaterials to improve wound healing is a critical clinical challenge and an active field of research. As it is well described that oxygen plays a critical role in almost each step of the wound healing process, in this work, an oxygen producing photosynthetic biomaterial was generated, characterized, and further modified to additionally release other bioactive molecules. Here, alginate hydrogels were loaded with the photosynthetic microalgae Chlamydomonas reinhardtii, showing high integration as well as immediate oxygen release upon illumination. Moreover, the photosynthetic hydrogel showed high biocompatibility in vitro and in vivo, and the capacity to sustain the metabolic oxygen requirements of zebrafish larvae and skin explants. In addition, the photosynthetic dressings were evaluated in 20 healthy human volunteers following the ISO-10993-10-2010 showing no skin irritation, mechanical stability of the dressings, and survival of the photosynthetic microalgae. Finally, hydrogels were also loaded with genetically engineered microalgae to release human VEGF, or pre-loaded with antibiotics, showing sustained release of both bioactive molecules. Overall, this work shows that photosynthetic hydrogels represent a feasible approach for the local delivery of oxygen and other bioactive molecules to promote wound healing. STATEMENT OF SIGNIFICANCE: As oxygen plays a key role in almost every step of the tissue regeneration process, the development of oxygen delivering therapies represents an active field of research, where photosynthetic biomaterials have risen as a promising approach for wound healing. Therefore, in this work a photosynthetic alginate hydrogel-based wound dressing containingC. reinhardtiimicroalgae was developed and validated in healthy skin of human volunteers. Moreover, hydrogels were modified to additionally release other bioactive molecules such as recombinant VEGF or antibiotics. The present study provides key scientific data to support the use of photosynthetic hydrogels as customizable dressings to promote wound healing.

Multi-scale computational investigation of Ag-doped two-dimensional Zn-based MOFs for storage and release of small NO and CO bioactive molecules.

Nitric oxide (NO) and carbon monoxide (CO) are two important gasotransmitters with critical biological roles in the human body. Due to their short lifetime and dangerous side effects at high concentrations, it is essential to find safe storage and slow release methods of these two gases. Herein, we report the multi-scale simulations of two-dimensional (Zn)MOF-470 doped with antimicrobial Ag atoms to evaluate the degree of enhancement of adsorption and dynamics of NO and CO. The results show that NO binds to Ag stronger than CO. In addition, the decoration of the benzene ring with Ag atoms on both sides has led to the effective adsorption of NO and CO with binding energies of -26.34 and -21.71 kcal mol-1, respectively. The GCMC results show that Ag can significantly improve NO and CO storage capacity, especially in low-pressure ranges. The storage capacity of NO in (Zn)MOF-470 and Ag-doped MOFs is 6.12 and 7.21 mol kg-1, respectively. This storage capacity for CO is 4.09 and 5.48 mol kg-1, respectively. The heat of adsorption for NO and CO was obtained to be 31.72 and 25.64 kJ mol-1 for (Zn)MOF-470, and 36.5 and 31.12 kJ mol-1 for Ag-(Zn)MOF-470 at 298 K and 1 bar. Besides, the MD results indicate that when Ag is doped into the structure of MOFs, the dynamics of gases within the pores of MOFs significantly decrease. When Ag atoms are considered mobile, the dynamics of guest molecules increase and it shows that the structural and dynamical behavior of NO and CO strongly depends on the mobility or immobility of doped Ag atoms. The result from the MSD directions (x, y, and z components) indicates that the diffusion of NO and CO within the pores of (Zn)MOF-470 is anisotropic and this may be due to the 2D structural characteristics of the MOF, the dipolar nature of NO and CO molecules, and the very narrow and layered pores of (Zn)MOF-470. These promising results from the simulations suggest that (Zn)MOF-470 and doping Ag atoms into this MOF can improve the storage capacity and slow release of bioactive NO and CO along with utilization of the antimicrobial nature of Ag atoms in medical applications.