Hyaluronic acid (HA) hydrogels are commonly used for facial dermal filling and for alternative medical aesthetic purposes. High diversity exists in commercial formulations, notably for the optimization of finished product stability, functionality, and performance. Polyvalent ingredients such as calcium hydroxylapatite (CaHA) or vitamin B3 (niacinamide) are notably used as bio-stimulants to improve skin quality attributes at the administration site. The aim of the present study was to perform multi-parametric characterization of two novel cross-linked dermal filler formulas (HAR-1 \"Instant Refine\" and HAR-3 \"Maxi Lift\") for elucidation of the various functional impacts of vitamin B3 incorporation. Therefore, the HAR products were firstly comparatively characterized in terms of in vitro rheology, cohesivity, injectability, and resistance to chemical or enzymatic degradation (exposition to H2O2, AAPH, hyaluronidases, or xanthine oxidase). Then, the HAR products were assessed for cytocompatibility and in vitro bio-stimulation attributes in a primary dermal fibroblast model. The results showed enhanced resilience of the cohesive HAR hydrogels as compared to JUVÉDERM® VOLBELLA® and VOLUMA® reference products in a controlled degradation assay panel. Furthermore, significant induction of total collagen synthesis in primary dermal fibroblast cultures was recorded for HAR-1 and HAR-3, denoting intrinsic bio-stimulatory effects comparable or superior to those of the Radiesse® and Sculptra™ reference products. Original results of high translational relevance were generated herein using robust and orthogonal experimental methodologies (hydrogel degradation, functional benchmarking) and study designs. Overall, the reported results confirmed the dual functionalization role of vitamin B3 in cross-linked HA dermal fillers, with a significant enhancement of hydrogel system stability attributes and the deployment of potent bio-stimulatory capacities.

Volumetric muscle loss (VML) injuries are characterized by a degree of tissue loss that exceeds the endogenous regenerative capacity of muscle, resulting in permanent structural and functional deficits. Such injuries are a consequence of trauma, as well as a host of congenital and acquired diseases and disorders. Despite significant preclinical research with diverse biomaterials, as well as early clinical studies with implantation of decellularized extracellular matrices, there are still significant barriers to more complete restoration of muscle form and function following repair of VML injuries. In fact, identification of novel biomaterials with more advantageous regenerative profiles is a critical limitation to the development of improved therapeutics. As a first step in this direction, we evaluated a novel semisynthetic hyaluronic acid-based (HyA) hydrogel that embodies material features more favorable for robust muscle regeneration. This HyA-based hydrogel is composed of an acrylate-modified HyA (AcHyA) macromer, an AcHyA macromer conjugated with the bsp-RGD(15) peptide sequence to enhance cell adhesion, a high-molecular-weight heparin to sequester growth factors, and a matrix metalloproteinase-cleavable cross-linker to allow for cell-dependent remodeling. In a well-established, clinically relevant rat tibialis anterior VML injury model, we report observations of robust functional recovery, accompanied by volume reconstitution, muscle regeneration, and native-like vascularization following implantation of the HyA-based hydrogel at the site of injury. These findings have important implications for the development and clinical application of the improved biomaterials that will be required for stable and complete functional recovery from diverse VML injuries.

Curcumin is a more efficient polyphenol than many chemotherapeutics. It can inhibit many signaling pathways at the same time resulting in modulation and down regulation for many oncogenic activities, tumor suppressor genes, several transcription factors and their signaling pathways. However it is still not employed as a potential therapeutic tool for cancer treatment. This is due to its hydrophobicity, its hypersensitivity and its poor adsorption. Many trials have been applied for encapsulating curcumin as a delivery system thinking to save its biological benefits. In our recent work, encapsulated curcumin was successfully used to produce bio cross-linkers for mucoadhesive polymer forming multi branched or flower like shape. Moreover, this strategy is not used only to save its biological function, but also to provide a novel bio cross-linker for hydrogel system. This study was investigated by using scanning electron microscopy, FTIR, U-V Visible Spectroscopy. Encapsulated curcumin provides promising bio safe cross-linker for optimizing hydrogel system, since carboxymethyl cellulose raises its ability to penetrate mucus layer. Additionally, flow cytometry and cytotoxicity show ability of encapsulated curcumin to inhibit proliferation of liver cancer cells.

The controlled release of active substances-bone morphogenetic protein 2 (BMP-2) and 17β-estradiol-is one of the main aspects to be taken into account to successfully regenerate a tissue defect. In this study, BMP-2- and 17β-estradiol-loaded microspheres were combined in a sandwich-like system formed by a hydrogel core composed of chitosan (CHT) collagen, 2-hidroxipropil γ-ciclodextrin (HP-γ-CD), nanoparticles of hydroxyapatite (nano-HAP), and an electrospun mesh shell prepared with two external electrospinning films for the regeneration of a critical bone defect in osteoporotic rats. Microspheres were made with poly-lactide-co-glycolide (PLGA) to encapsulate BMP-2, whereas the different formulations of 17β-estradiol were prepared with poly-lactic acid (PLA) and PLGA. The in vitro and in vivo BMP-2 delivered from the system fitted a biphasic profile. Although the in vivo burst effect was higher than in vitro the second phases (lasted up to 6 weeks) were parallel, the release rate ranged between 55 and 70 ng/day. The in vitro release kinetics of the 17β-estradiol dissolved in the polymeric matrix of the microspheres depended on the partition coefficient. The 17β-estradiol was slowly released from the core system using an aqueous release medium (Deff = 5.58·10-16 ± 9.81·10-17m2s-1) and very fast in MeOH-water (50:50). The hydrogel core system was injectable, and approximately 83% of the loaded dose is uniformly discharged through a 20G needle. The system placed in the defect was easily adapted to the defect shape and after 12 weeks approximately 50% of the defect was refilled by new tissue. None differences were observed between the osteoporotic and non-osteoporotic groups. Despite the role of 17β-estradiol on the bone remodeling process, the obtained results in this study suggest that the observed regeneration was only due to the controlled rate released of BMP-2 from the PLGA microspheres.

Kaolin can adhere to the mucosa and protect it by absorbing toxins, bacteria, and viruses. Ocular delivery and anti-inflammatory activity of dexamethasone hydrogel system could be advantageous after kaolin incorporation.
Hydroxypropyl methylcellulose (HPMC) films of dexamethasone have been prepared without and with kaolin by solvent casting method. Differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and scanning electron microscopy (SEM) were utilized for evaluating thermal property, crystallinity, and morphology of the film preparations respectively. In vitro drug release and corneal permeation ex vivo were carried out in phosphate buffer saline of pH 7.4 (PBS) at 34 ± 0.5°C for 6 h. Anti inflammatory effect of the prepared film was evaluated using carrageenan induced rabbit eye.
Disappearance of melting endotherm in the DSC thermogram is the indication of almost complete amorphization of drug in all the films. High-intensity reflections with characteristic peaks of pure drug crystal have resulted extensively reduced ordering of the crystal lattice in the X-ray pattern of all the films. Photomicrographs revealed that the plate-shaped geometry of the drug crystal has almost been lost in absence and presence of the nano-kaolin particles in the films. Kaolin incorporation controlled the drug release up to 6 h. Ocular permeation was diffusion controlled and extended for 6 h or more without exhibiting significant \"Burst effect\". Adsorption of drug onto the surface of nano-kaolin prolonged the permeation due to cation exchange and hydrogen bonding. Signs of inflammation of the carrageenan induced rabbit eye have been disappeared almost completely after 2 h of film application.
Local controlled delivery sustained anti-inflammatory activity of dexamethasone has been achieved using kaolin incorporated HPMC film.