Currently, surgical operations, followed by systemic drug delivery, are the prevailing treatment modality for most diseases, including cancers and trauma-based injuries. Although effective to some extent, the side effects of surgery include inflammation, pain, a lower rate of tissue regeneration, disease recurrence, and the non-specific toxicity of chemotherapies, which remain significant clinical challenges. The localized delivery of therapeutics has recently emerged as an alternative to systemic therapy, which not only allows the delivery of higher doses of therapeutic agents to the surgical site, but also enables overcoming post-surgical complications, such as infections, inflammations, and pain. Due to the limitations of the current drug delivery systems, and an increasing clinical need for disease-specific drug release systems, hydrogels have attracted considerable interest, due to their unique properties, including a high capacity for drug loading, as well as a sustained release profile. Hydrogels can be used as local drug performance carriers as a means for diminishing the side effects of current systemic drug delivery methods and are suitable for the majority of surgery-based injuries. This work summarizes recent advances in hydrogel-based drug delivery systems (DDSs), including formulations such as implantable, injectable, and sprayable hydrogels, with a particular emphasis on stimuli-responsive materials. Moreover, clinical applications and future opportunities for this type of post-surgery treatment are also highlighted.

Cell-imprinting technology is a novel method for directing stem cell fate using substrates molded from target cells. Here, we fabricated and studied cell-imprinted substrates for neural priming in human adipose-derived stem cells in the absence of chemical cues. We molded polydimethylsiloxane (PDMS) silicone substrates on fixed differentiated neural progenitor cells (ReNcellTM VM). The ReNcellTM cell line consists of immortalized human neural progenitor cells that are capable to differentiate into neural cells. The fabricated cell-imprinted silicone substrates represent the geometrical micro-and nanotopology of the target cell morphology. During the molding procedure, no transfer of cellular proteins was detectable. In the first test with undifferentiated ReNcellTM VM cells, the cell-imprinted substrates could accelerate neural differentiation. With adipose-derived stem cells cultivated on the imprinted substrates, we observed modifications of cell morphology, shifting from spread to elongated shape. Both immunofluorescence and quantitative gene expression analysis showed upregulation of neural stem cell and early neuronal markers. Our study, for the first time, demonstrated the effectiveness of cell-imprinted substrates for neural priming of adipose-derived stem cells for regenerative medicine applications.

Cell encapsulation within the microspheres using a semi-permeable polymer allows the two-way transfer of molecules such as oxygen, nutrients, and growth factors. The main advantages of cell encapsulation technology include controlling the problems involved in transplanting rejection in tissue engineering applications and reducing the long-term need for immunosuppressive drugs following organ transplantation to eliminate the side effects. Cell-laden microgels can also be used in 3D cell cultures, wound healing, and cancerous clusters for drug testing. Since cell encapsulation is used for different purposes, several techniques have been developed to encapsulate cells. Droplet-based microfluidics is one of the most valuable techniques in cell encapsulating. This study aimed to review the geometries and the mechanisms proposed in microfluidic systems to precisely control cell-laden microgels production with different biopolymers. We also focused on alginate gelation techniques due to their essential role in cell encapsulation applications. Finally, some applications of these microgels and researches will be explored.

Background Worldwide, many people suffer from knee injuries and articular cartilage damage every year, which causes pain and reduces productivity, life quality, and daily routines. Medication is currently primarily used to relieve symptoms and not to ameliorate cartilage degeneration. As the natural healing capacity of cartilage damage is limited due to a lack of vascularization, common surgical methods are used to repair cartilage tissue, but they cannot prevent massive damage followed by injury. Main body Functional tissue engineering has recently attracted attention for the repair of cartilage damage using a combination of cells, scaffolds (constructs), biochemical factors, and biomechanical stimuli. As cyclic biomechanical loading is the key factor in maintaining the chondrocyte phenotype, many studies have evaluated the effect of biomechanical stimulation on chondrogenesis. The characteristics of hydrogels, such as their mechanical properties, water content, and cell encapsulation, make them ideal for tissue-engineered scaffolds. Induced cell signaling (biochemical and biomechanical factors) and encapsulation of cells in hydrogels as a construct are discussed for biomechanical stimulation-based tissue regeneration, and several notable studies on the effect of biomechanical stimulation on encapsulated cells within hydrogels are discussed for cartilage regeneration. Conclusion Induction of biochemical and biomechanical signaling on the encapsulated cells in hydrogels are important factors for biomechanical stimulation-based cartilage regeneration.

No abstract