A variety of composite scaffolds with the specific porosity, pore size, and distinctive geometry required for tissue engineering (TE) can be fabricated with multipurpose 3-D printing techniques. However, the successful integration of biomaterials (scaffolds) with the human biological system remains a key challenge. Designing biomaterials with improved biological properties which induce minimal response is crucial. The primary goal of this project was to use fused deposition modeling (FDM) to fabricate 3-D printed composite scaffolds of polycaprolactone (PCL) and/or polylactic acid (PLA) incorporating bioactive glass (BG) particles, namely melt-derived particles from 45S5 BG (45 wt% SiO2, 24.5 wt% CaO, 24.5 wt% Na2O, 6.0 wt% P2O5), 13-93 BG (5.5 wt% Na2O, 11.1 wt% K2O, 4.6 wt% MgO, 18.5 wt% CaO, 56.6 wt% SiO2, and 3.7 wt% P2O4) and (borate) 13-93B3 BG (5.5 wt% Na2O, 11.1 wt% K2O, 4.6 wt% MgO, 18.5 wt% CaO, 3.7 wt% P2O4, 56.6 wt% B2O3), and then to enhance these scaffolds by various surface modification approaches to regulate the scaffold biological properties. To evaluate the chemical and surface properties of modified scaffolds, Fourier-transformed infrared spectroscopy (FTIR), contact angle, zeta potential, and scanning electron microscopy (SEM) were employed. All proposed surface-modifications of composite scaffolds led to attractive biological properties. For example, after surface modification, the adhesion of mesoporous bioactive glass nanoparticles (MBGNs) incorporated polymer-based composite coating was significantly improved. The use of secondary metabolites derived from therapeutic plants (phytotherapeutic agents) in TE applications is receiving increasing attention these days. In the last few years, a relatively new strategy of combining BGs with herb extracts (phytotherapeutic agents) to achieve better therapeutic outcomes and enhance the overall biological performance of the scaffolds has been gaining interest. The fabrication of 3-D printed scaffolds coated with composite material incorporating phytotherapeutic drugs resulting in enhanced biological activities is another approach followed in this study. Possible biological properties of phytotherapeutic agents (e.g., ferulic acid (FA), Boswellia sacra, and manuka honey (MH)) in conjunction with MBGNs were critically evaluated, summarizing the findings of research conducted on these organic-inorganic systems. The SEM and energy dispersive X-ray spectroscopy (EDX) evaluations of composite PLA scaffolds incorporated with 13-93 and 13-93B3 BGs showed the formation of a nano-hydroxyapatite (HA) surface layer after 14 days of immersion in simulated body fluid (SBF). However, the in vitro cellular activity of MG-63 and MC3T3-E1 osteoblastic cells showed that increased boron content in the BG inhibited cell proliferation. Moreover, an increase in mechanical strength was observed in all composite scaffolds. These findings provided valuable outcomes for further research to develop a new family of novel PCL-based composite scaffold and to functionalize these scaffolds with different surface modification techniques (including surface etching and mussel-inspired surface modification). The chemical and surface properties of the surface-modified scaffolds were analyzed by FTIR, wettability, and SEM. Results revealed that surface-modified composite scaffolds exhibited attractive physicochemical and biological properties. After the surface modification, the adhesion of a composite coating based on polymers (gelatin, hydroxypropyl cellulose (HPC), and/or ethyl cellulose (EC)) incorporated with MBGNs (compositions: 70S (70 wt% SiO2 and 30 wt% CaO), 58S (58 wt% SiO2, 37 wt% CaO, 5 wt% P2O5) and/or Sr- containing (5 wt%) Sr-MBGNs was significantly improved. Achieving efficient loading of phytotherapeutic compounds onto the surface of bioactive glass is challenging. Therefore, the present work aimed to prepare novel compositions to improve the release of phytotherapeutic agents. Amino-functionalized MBGNs loaded with the phytotherapeutic compounds Boswellia sacra extract (received from collaborators at the University of Bonn) were investigated. MBGNs were also incorporated with MH crosslinked with HPC. Furthermore, in the case of MBGNs incorporated with FA, the release of FA from the phase separation system (consisting of HPC and/or EC) was evaluated. It was revealed that multi-functional composite coatings containing MBGNs (70S, 58S, and Sr-MBGNs) incorporated with phytotherapeutic compounds (MH, FA, and Boswellia sacra) strengthened the scaffolds' antibacterial properties. Moreover, attachment and differentiation of MG-63 and MC3T3-E1 cells were enhanced by the presence of the phytotherapeutic agents. Furthermore, even after three days of immersion in SBF, the bioactivity of the surface-modified (coated) scaffolds was impacted and the deposition of a hydroxyapatite layer was observed. According to our findings, the incorporation of BG particles into the polymer matrix enhanced the physicochemical and biological properties of scaffolds. Considering all results together the present project confirmed that the strategy of surface modification followed by a functional coating to combine the properties of bioactive glass with phytotherapeutic agents signifies a cutting-edge approach toward the development of a new family of innovative 3D composite scaffolds for effective bone tissue healing and/or regeneration.
Kanwal Ilyas (2025) studied this question.