Mesenchymal stem cell (MSC) encapsulation technique has long been emerged in tissue engineering as it plays an important role in implantation of stem cells to regenerate a damaged tissue. MSC encapsulation provides a mimic of a three-dimensional (3D) in vivo environment to maintain cell viability and to induce the stem cell differentiation which regulates MSC fate into multi-lineages. Moreover, the 3D matrix surrounding MSCs protects them from the human innate immune system and allows the diffusion of biomolecules such as oxygen, cytokines, and growth factors. Therefore, many technologies are being developed to create MSC encapsulation platforms with diverse materials, shapes, and sizes. The conditions of the platform are determined by the targeted tissue and translation method. This review introduces several details of MSC encapsulation technologies such as micromolding, electrostatic droplet extrusion, microfluidics, and bioprinting and their application for tissue regeneration. Lastly, some of the challenges and future direction of MSC encapsulation technologies as a cell therapy-based tissue regeneration method will be discussed.

Intervertebral disc (IVD) is the fibrocartilage between the vertebrae, allowing the spine to move steadily by bearing multidirectional complex loads. Aging or injury usually causes degeneration of IVD, which is one of the main reasons for low back pain prevalent worldwide and reduced quality of life. While various treatment strategies for degenerative IVD have been studied using in vitro studies, animal experiments, and clinical trials, there are unsolved limitations for endogenous regeneration of degenerative IVD. In this respect, several tissue engineering strategies that are based on the cell and scaffolds have been extensively researched with positive outcomes for regeneration of IVD tissues. Scaffolds made of functional polymers and their diverse forms mimicking the macro- and micro-structure of native IVD enhance the biological and mechanical properties of the scaffolds for IVD regeneration. In this review, we discuss diverse morphological and functional polymers and tissue engineering strategies for endogenous regeneration of degenerative IVD. Tissue engineering strategies using functional polymers are promising therapeutics for fundamental and endogenous regeneration of degenerative IVD.

Nitric Oxide (NO) is a small molecule gasotransmitter synthesized by nitric oxide synthase in almost all types of mammalian cells. NO is synthesized by NO synthase by conversion of l-arginine to l-citrulline in the human body. NO then stimulates soluble guanylate cyclase, from which various physiological functions are mediated in a concentration-dependent manner. High concentrations of NO induce apoptosis or antibacterial responses whereas low NO circulation leads to angiogenesis. The bidirectional effect of NO has attracted considerable attention, and efforts to deliver NO in a controlled manner, especially through polymeric carriers, has been the topic of much research. This naturally produced signaling molecule has stood out as a potentially more potent therapeutic agent compared to exogenously synthesized drugs. In this review, we will focus on past efforts of using the controlled release of NO via polymer-based materials to derive specific therapeutic results. We have also added studies and our future suggestions on co-delivery methods with other gasotransmitters as a step towards developing multifunctional carriers.

New blood vessel formation is essential for tissue regeneration to deliver oxygen and nutrients and to maintain tissue metabolism. In the field of tissue engineering, in vitro fabrication of new artificial vessels has been a longstanding challenge. Here we developed a technique to reconstruct a microvascular system using a polycaprolactone (PCL)/gelatin nanofibrous structure and a co-culture system. Using a simple electrospinning process, we fabricated three-dimensional mesh scaffolds to support the sprouting of human umbilical vein endothelial cells (HUVECs) along the electrospun nanofiber. The co-culture with adipose-derived mesenchymal stem cells (ADSCs) supported greater sprouting of endothelial cells (ECs). In a two-dimensional culture system, angiogenic cell assembly produced more effective direct intercellular interactions and paracrine signaling from ADSCs to assist in the vascular formation of ECs, compared to the influence of growth factor. Although vascular endothelial growth factor and sphingosine-1-phosphate were present during the culture period, the presence of ADSCs was the most important factor for the construction of a cell-assembled structure in the two-dimensional culture system. On the contrary, HUVECs co-cultured on PCL/gelatin nanofiber scaffolds produced mature and functional microvessel and luminal structures with a greater expression of vascular markers, including platelet endothelial cell adhesion molecule-1 and podocalyxin. Furthermore, both angiogenic factors and cellular interactions with ADSCs through direct contact and paracrine molecules contributed to the formation of enhanced engineered blood vessel structures. It is expected that the co-culture system of HUVECs and ADSCs on bioengineered PCL/gelatin nanofibrous scaffolds will promote robust and functional microvessel structures and will be valuable for the regeneration of tissue with restored blood vessels.

The number of breast reconstruction surgeries has been increasing due to the increase in mastectomies. Surgical implants (the standard polydimethylsiloxane (PDMS) implants) are widely used to reconstruct breast tissues, however, it can cause problems such as adverse immune reactions, fibrosis, rupture, and additional surgery. Hence, polymeric fillers have recently garnered increasing attention as strong alternatives for breast reconstruction materials. Polymeric fillers offer noninvasive methods of reconstruction, thereby reducing the possible adverse effects and simplifying the treatment. In this study, we synthesized a 2-hydroxylethylmethacrylate (HEMA) and acrylamide (Am) copolymer (Poly(HEMA-Am)) by redox polymerization to be used as a biocompatible filler material for breast reconstruction. The synthesized hydrogel swelled in phosphate buffered saline (PBS) shows an average modulus of 50 Pa, which is a characteristic similar to that of the standard dermal acrylamide filler. To investigate the biocompatibility and cytotoxicity of the Poly(HEMA-Am) hydrogel, we evaluated an in vitro cytotoxicity assay on human fibroblasts (hFBs) and human adipose-derived stem cells (hADSCs) with the hydrogel eluate, and confirmed a cell viability of over 80% of the cell viability with the Poly(HEMA-Am) hydrogel. These results suggest our polymeric hydrogel is a promising filler material in soft tissue augmentation including breast reconstruction.