In the present study, a hybrid microsphere/hydrogel system, consisting of polyvinyl alcohol (PVA)/sodium alginate (SA) hydrogel incorporating PCL microspheres is introduced as a skin scaffold to accelerate wound healing. The hydrogel substrate was developed using the freeze-thawing method, and the proportion of the involved polymers in its structure was optimized based on the in-vitro assessments. The bFGF-encapsulated PCL microspheres were also fabricated utilizing the double-emulsion solvent evaporation technique. The achieved freeze-dried hybrid system was then characterized by in-vitro and in-vivo experiments. The results obtained from the optimization of the hydrogel showed that increasing the concentration of SA resulted in a more porous structure, and higher swelling ability, elasticity and degradation rate, but decreased the maximum strength and elongation at break. The embedding of PCL microspheres into the optimized hydrogel structure provided sustained and burst-free release kinetics of bFGF. Besides, the addition of drug-loaded microspheres led to no significant change in the degradation mechanism of the hydrogel substrate; however, it reduced its mechanical strength. Furthermore, the MTT assay represented no cytotoxic effect for the hybrid system. The in-vivo studies on a burn-wound rat model, including the evaluation of the wound closure mechanism, and histological analyses indicated that the fabricated scaffold efficiently contributed to promoting cell-induced tissue regeneration and burn-wound healing.

Droplet-based microfluidic systems have been employed to manipulate discrete fluid volumes with immiscible phases. Creating the fluid droplets at microscale has led to a paradigm shift in mixing, sorting, encapsulation, sensing, and designing high throughput devices for biomedical applications. Droplet microfluidics has opened many opportunities in microparticle synthesis, molecular detection, diagnostics, drug delivery, and cell biology. In the present review, we first introduce standard methods for droplet generation (i.e. passive and active methods) and discuss the latest examples of emulsification and particle synthesis approaches enabled by microfluidic platforms. Then, the applications of droplet-based microfluidics in different biomedical applications are detailed. Finally, a general overview of the latest trends along with the perspectives and future potentials in the field are provided.

Using the skin tissue engineering approach is a way to help the body to recover its lost skin in cases that the spontaneous healing process is either impossible or inadequate, such as severe wounds or burns. In the present study, chitosan/gelatin-based scaffolds containing 0.25, 0.5, 0.75, and 1% allantoin were created to improve the wounds’ healing process. EDC and NHS were used to cross-link the samples, which were further freeze-dried. Different in-vitro methods were utilized to characterize the specimens, including SEM imaging, PBS absorption and degradation tests, mechanical experiments, allantoin release profile assessment, antibacterial assay, and cell viability and adhesion tests. The results indicated that the scaffolds’ average pore sizes were approximately in the range of 390–440 µm, and their PBS uptake amounts were about 1000% to 1250% after being soaked in PBS for 24 h. Around 70% of the specimens were degraded in 6 days, but they were not fully degraded after 21 days. Besides, the samples showed antibacterial activity against S. aureus and E. coli bacteria. In general, the MTT cell viability test indicated that the cells’ density increased slightly or remained the same during the experiment. SEM images of cells seeded on the scaffolds indicated appropriate properties of the scaffolds for cell adhesion.

Fabrication of well-ordered and bio-mimetic scaffolds is one of the most important research lines in tissue engineering. Different techniques have been utilized to achieve this goal, however, each method has its own disadvantages. Recently, melt electrowriting (MEW) as a technique for fabrication of well-organized scaffolds has attracted the researchers’ attention due to simultaneous use of principles of additive manufacturing and electrohydrodynamic phenomena. In previous research studies, polycaprolactone (PCL) has been mostly used in MEW process. PCL is a biocompatible polymer with characteristics that make it easy to fabricate well-arranged structures using MEW device. However, the mechanical properties of PCL are not favorable for applications like bone tissue engineering. Furthermore, it is of vital importance to demonstrate the capability of MEW technique for processing a broad range of polymers. To address aforementioned problems, in this study, three ten-layered box-structured well-ordered scaffolds, including neat PLA, neat PCL, and PLA/PCL composite are fabricated using an MEW device. Printing of the composite PLA/PCL scaffold using the MEW device is conducted in this study for the first time. The MEW device used in this study is a commercial fused deposition modeling (FDM) 3D printer which with some changes in its setup and configuration becomes prepared for being used as an MEW device. Since in most of previous studies, a setup has been designed and built for MEW process, the use of the FDM device can be considered as one of the novelties of this research. The printing parameters are adjusted in a way that scaffolds with nearly equal pore sizes in the range of 140 µm to 150 µm are fabricated. However, PCL fibers are mostly narrower (diameters in the range of 5 µm to 15 µm) than PLA fibers with diameters between 15 and 25 µm. Unlike the MEW process of PCL, accurate positioning of PLA fibers is difficult which can be due to higher viscosity of PLA melt compared to PCL melt. The printed composite PLA/PCL scaffold possesses a well-ordered box structure with improved mechanical properties and cell-scaffold interactions compared to both neat PLA and PCL scaffolds. Besides, the composite scaffold exhibits a higher swelling ratio than the neat PCL scaffold which can be related to the presence of less hydrophobic PLA fibers. This scaffold demonstrates an anisotropic behavior during uniaxial tensile test in which its Young’s modulus, ultimate tensile stress, and strain to failure all depend on the direction of the applied tensile force. This anisotropy makes the composite PLA/PCL scaffold an exciting candidate for applications in heart tissue engineering. The results of in-vitro cell viability test using L929 mouse murine fibroblast and human umbilical vein endothelial (HUVEC) cells demonstrate that all of the printed scaffolds are biocompatible. In particular, the composite scaffold presents the highest cell viability value among the fabricated scaffolds. All in all, the composite PLA/PCL scaffold shows that it can be a promising substitution for neat PCL scaffold used in previous MEW studies.