Mihaela Violeta Ghica

Collagen Wound Dressings with Anti-Inflammatory Activity

The aim of this study was to develop modern wound dressings such as controlled drug delivery systems. These systems consist in collagen as release support and niflumic acid as drug. The scaffolds were prepared by lyophilization in order to obtain porous structures and were evaluated by release profile of niflumic acid, water absorption, collagenase degradation and biocompatibility with fibroblast cells. The collagen scaffold with 0.75% niflumic acid solved in laurel oil was optimal in terms of biodegradability, absorbability and fibroblast cells biocompatibility. Thus, the obtained collagen scaffolds could be used as wound dressings with absorbent, antibacterial and anti-inflammatory properties.

Collagen-Based Drug Delivery Systems for Tissue Engineering

Biomaterials are considered those natural or artificial materials that can be used for any period of time, as a whole or as part of a system which treats, augments or replaces a tissue, organ or function of the human or animal body (Williams, 1999). In medicine a wide range of biomaterials based on metals, ceramics, synthetic polymers, biopolymers, etc. is used. Among biopolymers, collagen represents one of the most used biomaterials due to its excellent biocompatibility, biodegradability and weak antigenecity, well-established structure, biologic characteristics and to the way it interacts with the body, the latter recognizing it as one of its constituents and not as an unknown material (Friess, 1998; Lee et al., 2001). Irrespective of the progress in the field of biomaterials based on synthetic polymers, collagen remains one of the most important natural biomaterials for connective tissue prosthetic in which it is the main protein. Due to its excellent properties collagen can be processed in different biomaterials used as burn/wound dressings, osteogenic and bone filling materials, antithrombogenic surfaces, collagen shields in ophthalmology, being also used for tissue engineering including skin replacement, bone substitutes, and artificial blood vessels and valves. Biomaterials based on type I fibrillar collagen such as medical devices, artificial implants, drug carriers for controlled release and scaffolds for tissue regeneration have an important role in medicine, being widely used at present (Healy et al., 1999; Hubell, 1999; Wang et al., 2004). In this chapter, we attempted to summarize some of the recent developments in the application of collagen as biomaterial in drug delivery systems and tissue engineering field.

Doxycycline Delivery From Collagen Matrices Crosslinked With Tannic Acid

Collagen-doxycycline matrices crosslinked with a natural polyphenol – tannic acid for the treatment of infected wounds were obtained by the freeze-drying of the corresponding gels. FT-IR spectra show that the triple helical structure of collagen is preserved in all the matrices, doxycycline produce collagen crosslinking and the degree of crosslinking increases with tannic acid concentration. Digestion of matrices using collagenase confirms the crosslinking effect of doxycycline and tannic acid and the increasing of the crosslinking degree with the amount of acid. The release of doxycycline from the matrices crosslinked with tannic acid is slower than that from the uncrossliked one and decreases with increasing of acid concentration, according to FT-IR and digestion results, and follows the power law model, with a release exponent of about 0.4, which indicates an anomalous transport. The matrices containing doxycycline, tannic acid and their combination do not develop gram-positive (Staphylococcus aureus) or gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria, fungi or leavens.

New collagen-dextran-zinc oxide composites for wound dressing

The goal of this paper was the design, development, and characterization of some new composites, based on collagen and dextran as natural polymers and zinc oxide as antimicrobial, to be used in wound healing. Collagen hydrogels with various concentrations of dextran and zinc oxide were investigated in terms of rheological analysis. The spongious composites, obtained by freeze-drying of hydrogels, were evaluated by morphology (SEM), water uptake, and biological (enzymatic biodegradation) analysis. All the results were strongly influenced by the nature and concentration of composite components. Based on the performances of the hydrogels, stationary rheometry, porous structure, morphology, and biological behavior, the antimicrobial spongious composite based on collagen and dextran with 50% ZnO were the most promising for future applications in wound dressing and a biomaterial with high potential in skin regeneration.

Modification of titanium surface with collagen and doxycycline as a new approach in dental implants

In this work, we investigate for the first time several issues involved in bio-adhesion process for a new type of chemically modified titanium surfaces (in their initial form and after collagen deposition), in order to assess their potential in dental implant surface modification. For this purpose, we studied the following: collagen adhesion, cytotoxicity, osteoblast cytomorphology, cell adhesion and proliferation, doxycycline embedding and modifications in the collagen film deposed on the metal surfaces, drug release from the collagen films. The improvement of adhesion between collagen film and titanium substrate, when hydroxyl and amino functional groups are assisting the surfaces was presented, all materials showing no cytotoxic effects as revealed by lactate dehydrogenase-based assay. The drug release from titanium–coll–doxy systems offers a dual mechanism of the delivery profile (burst release followed by moderate discharge of the antibiotic), with perspectives in soft tissue recovery postoperative stage.

Flow and Thixotropic Parameters for Rheological Characterization of Hydrogels

The goal of this paper was to design several sodium carboxymethylcellulose hydrogels containing a BCS class II model drug and to evaluate their flow and thixotropic properties. The rheological measurements were performed at two temperatures (23 °C and 37 °C), using a rotational viscometer. The hydrogels were stirred at different time intervals (10 s, 2, 5, 10 and 20 min at 23 °C, and 10 s, 2 and 5 min at 37 °C), with a maximum rotational speed of 60 rpm, and the corresponding forward and backward rheograms were recorded as shear stress vs. shear rate. For all hydrogels, the rheological data obtained at both temperatures showed a decrease of viscosity with the increase of the shear rate, highlighting a pseudoplastic behaviour. The flow profiles viscosity vs. shear rate were quantified through power law model, meanwhile the flow curves shear stress vs. shear rate were assessed by applying the Herschel-Bulkley model. The thixotropic character was evaluated through different descriptors: thixotropic area, thixotropic index, thixotropic constant and destructuration thixotropic coefficient. The gel-forming polymer concentration and the rheological experiments temperature significantly influence the flow and thixotropic parameters values of the designed hydrogels. The rheological characteristics described have an impact on the drug release microenvironment and determine the stasis time at the application site.

Superhydrophobic Natural and Artificial Surfaces—A Structural Approach

Since ancient times humans observed animal and plants features and tried to adapt them according to their own needs. Biomimetics represents the foundation of many inventions from various fields: From transportation devices (helicopter, airplane, submarine) and flying techniques, to sports’ wear industry (swimming suits, scuba diving gear, Velcro closure system), bullet proof vests made from Kevlar etc. It is true that nature provides numerous noteworthy models (shark skin, spider web, lotus leaves), referring both to the plant and animal kingdom. This review paper summarizes a few of “nature’s interventions” in human evolution, regarding understanding of surface wettability and development of innovative special surfaces. Empirical models are described in order to reveal the science behind special wettable surfaces (superhydrophobic /superhydrophilic). Materials and methods used in order to artificially obtain special wettable surfaces are described in correlation with plants’ and animals’ unique features. Emphasis is placed on joining superhydrophobic and superhydrophilic surfaces, with important applications in cell culturing, microorganism isolation/separation and molecule screening techniques. Bio-inspired wettability is presented as a constitutive part of traditional devices/systems, intended to improve their characteristics and extend performances.

Innovative Biomaterials Based on Collagen-Hydroxyapatite and Doxycycline for Bone Regeneration

Bone regeneration is a serious challenge in orthopedic applications because of bone infections increase, tumor developing, and bone loss due to trauma. In this context, the aim of our study was to develop innovative biomaterials based on collagen and hydroxyapatite (25, 50, and 75%) which mimic bone composition and prevent or treat infections due to doxycycline content. The biomaterials were obtained by freeze-drying in spongious forms and were characterized by water uptake capacity and microscopy. The in vitro release of doxycycline was also determined and established by non-Fickian drug transport mechanism. Among the studied biomaterials, the most suitable one to easily deliver the drug and mimic bone structure, having compact structure and lower capacity to uptake water, was the one with 75% hydroxyapatite and being cross-linked.

Development, Optimization and In Vitro/In Vivo Characterization of Collagen-Dextran Spongious Wound Dressings Loaded with Flufenamic Acid

The aim of this study was the development and optimization of some topical collagen-dextran sponges with flufenamic acid, designed to be potential dressings for burn wounds healing. The sponges were obtained by lyophilization of hydrogels based on type I fibrillar collagen gel extracted from calf hide, dextran and flufenamic acid, crosslinked and un-crosslinked, and designed according to a 3-factor, 3-level Box-Behnken experimental design. The sponges showed good fluid uptake ability quantified by a high swelling ratio. The flufenamic acid release profiles from sponges presented two stages-burst effect resulting in a rapid inflammation reduction, and gradual delivery ensuring the anti-inflammatory effect over a longer burn healing period. The resistance to enzymatic degradation was monitored through a weight loss parameter. The optimization of the sponge formulations was performed based on an experimental design technique combined with response surface methodology, followed by the Taguchi approach to select those formulations that are the least affected by the noise factors. The treatment of experimentally induced burns on animals with selected sponges accelerated the wound healing process and promoted a faster regeneration of the affected epithelial tissues compared to the control group. The results generated by the complex sponge characterization indicate that these formulations could be successfully used for burn dressing applications.

Chitosan-Based In Situ Gels for Ocular Delivery of Therapeutics: A State-of-the-Art Review

Ocular in situ gels are a promising alternative to overcome drawbacks of conventional eye drops because they associate the advantages of solutions such as accuracy and reproducibility of dosing, or ease of administration with prolonged contact time of ointments. Chitosan is a natural polymer suitable for use in ophthalmic formulations due to its biocompatibility, biodegradability, mucoadhesive character, antibacterial and antifungal properties, permeation enhancement and corneal wound healing effects. The combination of chitosan, pH-sensitive polymer, with other stimuli-responsive polymers leads to increased mechanical strength of formulations and an improved therapeutic effect due to prolonged ocular contact time. This review describes in situ gelling systems resulting from the association of chitosan with various stimuli-responsive polymers with emphasis on the mechanism of gel formation and application in ophthalmology. It also comprises the main techniques for evaluation of chitosan in situ gels, along with requirements of safety and ocular tolerability.