The additive manufacturing, in which two or more materials come together and the structures are formed with a 3D printer, is a potential method for regenerative medicine for implants,stem cells delivery carriers in stem cellstransplantations, or controlled drug delivery carriers, [1], [2], [3], [4], [5]. To provide the desired duration and release kinetics of drugs, biocompatible polymer scaffolds should have optimal composition and structure In contrast to the duration and kinetics of the release, the structure of the polymer scaffold ensures that the therapeutic composition containing the active substance is protected in the body from drug release. The preservation of the active ingredient in the polymer prevents fluctuations in drug levels that can occur simultaneously with sequential and ad hoc drug administration. This condition, gains more importance as the drug content increases, aims to achieve a spatial- temporal release model specific to the treatment site in contrary to conventional drug release systems [6].

Sustained release of a hydrophilic drug from the hydrophobic polymer carrier might be difficult, and phase separation and splitting of the drug from the matrix may occur, causing sudden release of the active substance [7]. In a layered scaffold-drug delivery system the hydrophilic drug can be preserved in a hydrophilic polymer in a form of particles, and integrated into the hydrophobic scaffold allowing for a longer and more stable release. This kinf od system have many advantages since it can provide physical bonds between biological parts such as cells and scaffolds due to drug and polymer scaffolds cell retention capacity [8].

Tetracycline (Tet) is an antibiotic used in the prophylaxis and treatment of both human and animal infections against microorganisms such as gram-positive and gram-negative bacteria, protozoa, parasites, and mycoplasmas [9], [10], [11]. Tet, which has a versatile and changeable structure, has been used in the treatment of diseases for more than half a century now due to its chemical backbone that interact with the cellular target [12]. Basically, in the working mechanism of Tet antibiotic interfere with bacterial proteins by binding to them at the site of biosynthesis through the 30S subunit of the bacterial ribosome. The mechanism of action of tetracyclines makes it impossible for bacteria to attach tRNA and in consequence the inhibition of the development of the bacterial cell occurs.[11]. Tet is used clinically for bacterial dysentery [13], trachoma [14], pertussis [15], pneumonia [12], purulent meningitis [16], skin infections [17], and otitis media [18]. In the study of Karuppuswamy et al used PCLnanofibes enriched with Tet in different concentrations and tested the influence of the concentration of the drug on on the speed of tissue regeneration. The combination of PCL and Tet was found to be potential as a substrate for drug delivery carriers and scaffolds.

PCL is a low cost biodegradable, biocompatible, synthetic material, possessing good mechanical properties, that is satisfactory for many tissue engineering and drug delivery applications. On of the best methods to transform this polymer into scaffolds is 3D printing due to ease procesability and low melting temperature of the polymer. 3D printing is a very sufficient method for fabrication of complicated multilayer 3D structures with complex geometry and high porosity. Moreover, 3D scaffolds sustains micro-environments more accurately mimicking complex structure of the native tissues [19].

There are several techniques to produce nano- and microsized polymeric particles. These includes coacervation/precipitation, ionic gelation, spray drying, solvent evaporation, and electrospray.The electrospray method is an easy way to encapsulate drugs, and it can be performed in one step or multi-step process to produce the particles of desired sizes [20]. The electrospray technique can be utilized for advanced engineering application, and it allows to produce droplets of desired dimateres and morphologies from solutions or melts [21].

Polyvinylpyrrolidone (PVP) is one of the materials utilized for particles’ matrix formation. It is a it is biocompatible, hemocompatible, low toxic, pH-stable polymers possessing high chemical and thermal resistance. Thanks to its special features the encapsulated active substance can be released in a controllable manner [22]. Guastaferro et al. obtained PVP particles with sizes of 140 ± 14 nm using electrospray for the development of rutin and quercetin with with antioxidant properties [23], [24]. Xu et al. used sodium alginate, polydopamine, and PVP to produce doxorubicin encapsulated particles using electrospraying to develop systems for cancer therapy. The studies have proven that the colloidal stability of the produced material is provided by PVP molecules, and the photothermal conversion efficiency of 27.4 % and anti-tumor therapeutic performance have been obtained [25]. Rose et al. used epirubicin hydrochloride drug adsorbed on the surface of magnetite (Fe3O4) nanoparticles coated and non-coated with PVP For selective cancer therapy. Results of the studies showed that nanoparticles coated with PVP were successful in killing tumor cells, showing 81 % growth inhibition [26].

In this study, polycaprolactone 3D scaffolds of different designs containing Polyvinylpyrrolidone nanoparticles, encapsulated with the hydrophilic drug Tet were fabricated. The influence of the scaffolds design and drug enrichment on the physical and chemical properties, drug release profiles, and in vitro cell viability were investigated. By combining 3D scaffolds and drug-loaded nanoparticles, it is aimed to design a safer, more controlled and more efficient drug delivery system, and to develop new functional scaffolds.