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Depending on the concentration of the drug and/or the method of administration, drugs could be used in various ways. To take full advantage of the drug beneficial properties in oral medical interventions but also in other types of surgery, like plastic surgery, general surgery, or gynecological surgery, the drug concentration as well as the administration method itself will depend on the wound, type of surgery, and severity of the postoperative pain which can be very different. Generally, the local administration methods are recommended. Piroxicam, a nonsteroidal anti-inflammatory drug (NSAID) of the oxicam class, is generally used to relieve the symptoms of pain and inflammation. Starting from the idea of the special benefit of the interference between collagen-based materials and drug beneficial properties, our work was focused on the synthesis and characterization of new collagen-piroxicam materials. These new collagen-based materials present a good water absorption, and the piroxicam release suggests a biphasic drug release profile whereas the obtained values for the release exponent revealed a complex release mechanism including swelling, diffusion, and erosion.

Microbial infections associated with skin diseases are frequently investigated since they impact on the progress of pathology and healing. The present work proposes the development of freeze-dried, glutaraldehyde cross-linked, and non-cross-linked biocomposite dressings with a porous structure, which may assist the reepithelization process through the presence of collagen and carboxymethylcellulose, along with a therapeutic antimicrobial effect, due to silver nanoparticles (AgNPs) addition. Phisyco-chemical characterization revealed the porous morphology of the obtained freeze-dried composites, the presence of high crystalline silver nanoparticles with truncated triangular and polyhedral morphologies, as well as the characteristic absorption bands of collagen, silver, and carboxymethylcellulose. In vitro tests also assessed the stability, functionality, and the degradability rate of the obtained wound-dressings. Antimicrobial assay performed on Gram-negative (Escherichia coli), Gram-positive (Staphyloccocus aureus) bacteria, and yeast (Candida albicans) models demonstrated that composite wound dressings based on collagen, carboxymethylcellulose, and AgNPs are suitable for skin lesions because they prevent the risk of infection and have prospective wound healing capacity. Moreover, the cell toxicity studies proved that the obtained materials can be used in long time treatments, with no cytotoxic effects.

Compared to the classical systemic administration, the local drug release has some advantages, such as lack of systemic toxicity and associated side effects, increased patient compliance, and a low rate of bacterial resistance. Biopolymers are widely used to design sustained drug delivery systems and biomaterials for tissue engineering. Type II collagen is the indispensable component in articular cartilage and plays a critical role in the growth and proliferation process of chondrocytes. Thus, type II collagen has drawn more attention and interest in the treatment and research of the cartilage regeneration. The aim of this study was to obtain, characterize, and optimize the microcapsules formulation based on type II collagen, sodium alginate, and sodium carboxymethyl cellulose loaded with doxycycline as an antibiotic model drug that could be incorporated further in hydrogels to improve the localized therapy of septic arthritis. The new synthesized microcapsules were assessed by spectral (FT-IR), morphological (optical microscopy), and biological analysis (enzymatic biodegradation, antimicrobial activity). The size distribution of the obtained microcapsules was determined using optical microscopy. The drug encapsulation efficiency was also determined. To optimize the microcapsules&rsquo, composition, some physical-chemical and biological analyses were subjected to an optimization technique based on experimental design, response surface methodology, and the Taguchi technique, and the adequate formulations were selected. The results obtained recommend these new microcapsules as promising drug systems to be further incorporated in type II collagen hydrogels used for septic arthritis.

We report in this paper the synthesis and characterization of a new collagen-based material. This material was obtained in a spongy form and was functionalized with an antibiotic, ciprofloxacin. The targeted applications of these kind of materials concern the post-operative prophylaxis. The in vitro tests (antimicrobial, cytotoxic, drug release) showed that sponges with a concentration of 0.75 g of ciprofloxacin per gram of collagen could be beneficial for the desired applications.

This paper presents a new way to obtain collagen/hydroxyapatite (COLL/HA) composite materials by 3D printing. Because of high tendency of segregation of COLL/HA composite materials, printing was done using COLL/Ca2+ gel (even COLL/Ca(OH)2) followed by precipitation of HA and crosslinking of COLL. The HA precipitation occurs simultaneously with crosslinking of COLL molecules, these processes being assured by the presence of glutaraldehyde supplemented PBS solution. By printing with COLL/Ca2+ at acidic pH homogeneity was increased. FTIR spectroscopy and microscopy reveal HA formation as the main inorganic phase these nanoparticles being homogeneously dispersed in the volume. In vitro biocompatibility assays were performed on Vero cells (ISO10993-5/2009). Results show that the extract of the developed biomaterial in cell culture medium elicited a similar cellular response to standard culture medium demonstrating its potential for biomedical applications. The described procedure and proposed ink can be used for developing 3D bone scaffolds and open new perspectives for COLL/Ca2+ homogeneous inks.

It is well known that periodontitis causes rapid destruction of gingival and bone tissues. Topical treatments are suitable because the drug can be delivered in a proper and controlled concentration. Metronidazole proved to be efficient for patients with aggressive periodontitis. By this study we aimed to obtain spongious drug delivery systems for local periodontitis treatment based on collagen, strontium renalate and metronidazole. Collagen spongious forms were obtained by lyophilisation of composite gels based on collagen:strontium ranelate (50:50) and different concentrations of metronidazole. The obtained spongious forms were characterized by FT-IR, water up-take, optic microscopy and in vitro release of metronidazole. The prepared matrices absorbed a maximum amount of water after 30 min. The most absorbent sample is the reference one (only collagen) which absorbed about 35% water; the adding of metronidazole decrease the water absorption due to its lipophilic behavior. The samples with strontium are more compact and they absorbed less water than the ones without strontium. Because the samples were not cross-linked they degrade during 24 hours of water absorption process. The drug percentage released was influenced by the drug and strontium ranelate concentrations. The analysis performed sponges indicate that these composites can be useful as drug delivery supports.

The pain management is therefore of paramount importance and the local anesthetic treatment has to be considered. Thus, the purpose of this study was to design and characterize some collagen microcapsules incorporating an anesthetic. The collagen hydrolysate was prepared by spray-drying forming micro sizes spheres (microcapsules) which were loaded with 1% lidocaine (anesthetic) and cross-linked with different cross-linking agent: tannic acid, glutaraldehyde and genipin, in order to obtain solution for tooth pain. The wetting behavior of dried microcapsules powders was determined by contact angle measurement. The microcapsule solutions were characterized by dynamic light scattering (DLS) and in vitro release of lidocaine was investigated. These therapeutically products, based on collagen microcapsules, a local anesthetic and three cross-linking agents, could have potential biomedical application in tooth pain healing treatment.

The aim of this study is to design, develop and evaluate new biohybrid sponges based on polymers (collagen and polyvinyl alcohol) with and without indomethacin as anti-inflammatory drug model to be used for tissue regeneration in wound healing. Type I fibrillar collagen in the form of a gel and different concentrations of polyvinyl alcohol were mixed together to prepare composite gels. Both control samples, without indomethacin and with indomethacin, were obtained. All samples were crosslinked with glutaraldehyde. By freeze-drying of hydrogels, the spongious forms (matrices) were obtained. The matrices were characterized by FT-IR spectroscopy, scanning electron microscopy (SEM), water absorption, enzymatic degradation and in vitro indomethacin release. The pharmacological effect of the spongious biohybrid matrices was determined on an experimental model of burns induced to Wistar rats. The SEM images showed a porous structure with interconnected pores. Collagen sponges present a structure with pore sizes between 20 and 200 &micro, m, which became more and more compact with polyvinyl alcohol addition. The FT-IR showed interactions between collagen and polyvinyl alcohol. The enzymatic degradation indicated that the most stable matrix is the one with the ratio 75:25 of collagen:polyvinyl alcohol (ACI75), the other ones being degradable in time. The kinetic data of indomethacin release from matrices were fitted with different kinetic models and highlighted a biphasic release of the drug. Such kinetic profiles are targeted in skin wound healing for which important aspects are impaired inflammation and local pain. The treatment with sponges associated with anti-inflammatory drug had beneficial effects on the healing process in experimentally induced burns compared to the corresponding matrices without indomethacin and the classical treated control group.

Many research studies are directed toward developing safe and efficient collagen-based biomaterials as carriers for drug delivery systems. This article presents a comparative study of the properties of new collagen sponges prepared and characterized by different methods intended for biomedical applications. The structural integrity is one of the main properties for a biomaterial in order for it to be easily removed from the treated area. Thus, the effect of combining a natural polymer such as collagen with an antimicrobial drug such as oxytetracycline or doxycycline and glutaraldehyde as the chemical cross-linking agent influences the cross-linking degree of the material, which is in direct relation to its resistance to collagenase digestion, the drug kinetic release profile, and in vitro biocompatibility. The enzymatic degradation results identified oxytetracycline as the best inhibitor of collagenase when the collagen sponge was cross-linked with 0.5% glutaraldehyde. The drug release kinetics revealed an extended release of the antibiotic for oxytetracycline-loaded collagen sponges compared with doxycycline-loaded collagen sponges. Considering the behavior of differently prepared sponges, the collagen sponge with oxytetracycline and 0.5% glutaraldehyde could represent a viable polymeric support for the prevention/treatment of infections at the application site, favoring tissue 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. Thein vitrorelease 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.