Ciprofloxacin-loaded calcium alginate wafers prepared by freeze-drying technique for potential healing of chronic diabetic foot ulcers

Calcium alginate (CA) wafer dressings were prepared by lyophilization of hydrogels to deliver ciprofloxacin (CIP) directly to the wound site of infected diabetic foot ulcers (DFUs). The dressings were physically characterized by scanning electron microscopy (SEM), texture analysis (for mechanical and in vitro adhesion properties), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). Further, functional properties essential for wound healing, i.e., porosity, in vitro swelling index, water absorption (Aw), equilibrium water content (EWC), water vapor transmission rate (WVTR), evaporative water loss (EWL), moisture content, in vitro drug release and kinetics, antimicrobial activity, and cell viability (MTT assay) were investigated. The wafers were soft, of uniform texture and thickness, and pliable in nature. Wafers showed ideal wound dressing characteristics in terms of fluid handling properties due to high porosity (SEM). XRD confirmed crystalline nature of the dressings and FTIR showed hydrogen bond formation between CA and CIP. The dressings showed initial fast release followed by sustained drug release which can inhibit and prevent re-infection caused by both Gram-positive and Gram-negative bacteria. The dressings also showed biocompatibility (> 85% cell viability over 72 h) with human adult keratinocytes. Therefore, it will be a potential medicated dressing for patients with DFUs infected with drug-resistant bacteria

Wound dressings as growth factor delivery platforms for chronic wound healing

Introduction: Years of tissue engineering research have clearly demonstrated the potential of integrating growth factors (GFs) into scaffolds for tissue regeneration, a concept that has recently been applied to wound dressings. The old concept of wound dressings that only take a passive role in wound healing has now been overtaken, and advanced dressings which can take an active part in wound healing, are of current research interest. Areas covered: In this review we will focus on the recent strategies for the delivery of GFs to wound sites with an emphasis on the different approaches used to achieve fine tuning of spatial and temporal concentrations to achieve therapeutic efficacy. Expert opinion: The use of GFs to accelerate wound healing and reduce scar formation is now considered a feasible therapeutic approach in patients with a high risk of infections and complications. The integration of micro–and nanotechnologies into wound dressings could be the key to overcome the inherent instability of GFs and offer adequate control over the release rate. Many investigations have led to encouraging outcomes in various in vitro and in vivo wound models, and it is expected that some of these technologies will satisfy clinical needs and will enter commercialization

Alginate Self‐Crosslinking Ink for 3D Extrusion‐Based Cryoprinting and Application for Epirubicin‐HCl Delivery on MCF‐7 Cells

3D‐printed hydrogels are particularly advantageous as drug‐delivery platforms but their loading with water‐soluble active compounds remains a challenge requiring the development of innovative inks. Here, we propose a new 3D extrusion‐based approach that, by exploiting the internal gelation of the alginate, avoids the post‐printing crosslinking process and allows the loading of epirubicin‐HCl (EPI). The critical combinations of alginate, calcium carbonate and d‐ glucono‐δ‐lactone (GDL) combined with the scaffold production parameters (extrusion time, temperature, and curing time) were evaluated and discussed. The internal gelation in tandem with 3D extrusion allowed the preparation of alginate hydrogels with a complex shape and good handling properties. The dispersion of epirubicin‐HCl in the hydrogel matrix confirmed the potential of this self‐crosslinking alginate‐based ink for the preparation of 3D‐printed drug‐delivery platforms. Drug release from 3D‐printed hydrogels was monitored, and the cytotoxic activity was tested against MCF‐7 cells. Finally, the change in the expression pattern of anti‐apoptotic, pro-apoptotic, and autophagy protein markers was monitored by liquid‐chromatography tandem-mass‐spectrometry after exposure of MCF‐7 to the EPI‐loaded hydrogels

3D-printed scaffold composites for the stimuli-induced local delivery of bioactive adjuncts

Polysaccharide scaffolds have been successfully employed to reconstruct environments that sustain skin tissue regeneration after injuries. Three-dimensional (3D) advanced additive manufacturing technologies allow creating scaffolds with controlled and reproducible macro- and micro-structure that improve the quality of the restored tissue to favor spontaneous repair. However, when persistent inflammation occurs, the physiological tissue healing capacity is reduced, like in the presence of pathologies like diabetes, vascular diseases, chronic infection, and others. In these circumstances, the bioavailability of therapeutic adjuncts like the growth factors in addition to the standard treatments represents undoubtedly a promising strategy to accelerate the healing of skin lesions. Precisely designed polysaccharide scaffolds obtained by 3D printing represent a robust platform that can be further implemented with the controlled delivery of bioactive adjuncts. Human elastin-like polypeptides (HELPs) are stimuli-responsive biopolymers. Their structure allows the integration of domains endowed with biological functionality, making them attractive compounds to prepare composites with smart properties. In the present study, 3D-printed alginate and chitosan scaffolds were combined with the HELP components. The HELP biopolymer was fused to the epidermal growth factor (EGF) as the bioactive domain. Different constructs were prepared and the stimuli-responsive behavior as well as the biological activity were evaluated, suggesting that these smart bioactive composites are suitable to realize multifunctional dressings that sustain the local release of therapeutic adjuncts

Elastolytic-sensitive 3D-printed chitosan scaffold for wound healing applications

The combination of a chitosan 3D-printed scaffold with a hydrogel matrix containing an elastin-like polypeptide functionalized with the epidermal growth factor (HEGF) was evaluated as a possible strategy to obtain a bioactive platform with stimuli-responsive properties. We designed a chitosan/HEGF hybrid scaffold and examined the physico-chemical properties and the in vitro behavior when in contact with simulated biological fluids. Primary human dermal fibroblasts (hDFs) were used to test the in vitro cytocompatibility. Overall, these data provide first insights into the integration of HEGF-based hydrogel with 3D-printed scaffolds, contributing towards the rational design of a new smart functional wound dressing