Genipin Cross-Linked Decellularized Nucleus Pulposus Hydrogel-Like Cell Delivery System Induces Differentiation of ADSCs and Retards Intervertebral Disc Degeneration

Intervertebral disc degeneration (IDD) is the pathological basis of disc degenerative diseases (DDD). Reduction in the number of cells and degeneration of the extracellular matrix (ECM) in the nucleus pulposus (NP) are characteristics of IDD. Bio-hydrogel combined with stem cell transplantation is a promising treatment. Injectable ECM hydrogels have good biological activity and in-situ gelatinization. However, its biomechanics and stability are insufficient to provide adequate mechanical support for intervertebral discs and to maintain the long-term differential stimulus for seeded stem cells. In our study, we developed genipin cross-linked decellularized nucleus pulposus hydrogel (GDH) as delivery system. We evaluated the mechanical properties, stability, biocompatibility, and differentiation induction of GDH cross-linked with different concentrations of genipin in vitro. The GDH-loaded adipose-derived mesenchymal stem cells (ADSCs) (GDHA) were injected into the rat degenerated coccygeal intervertebral disc. The effect of intervertebral disc regeneration in vivo was evaluated. The results showed that GDH with 0.02% of genipin had similar elastic modulus to human nucleus pulposus, good biocompatibility, and inducibility of expressing NP-related genes. In vivo studies showed that GDHA improved the survival of ADSCs and improved the intervertebral height, MRI index, and histological grading score. In conclusion, GDH, as an outstanding bio-hydrogel cell delivery system, has the therapeutic potential for retarding IDD.

Delivery of CAR-T Cells in a Transient Injectable Stimulatory Hydrogel Niche Improves Treatment of Solid Tumors

Adoptive cell therapy (ACT) has proven to be highly effective in treating blood cancers such as B cell malignancies, but traditional approaches to ACT are poorly effective in treating the multifarious solid tumors observed clinically. Locoregional cell delivery methods have shown promising results in treating solid tumors compared to standard intravenous delivery methods, but the approaches that have been described to date have several critical drawbacks ranging from complex manufacturing and poor modularity to challenging adminstration. In this work, we develop a simple-to-implement self-assembled and injectable hydrogel material for the controlled co-delivery of CAR-T cells and stimulatory cytokines that improves treatment of solid tumors. We evaluate a range of hydrogel formulations to optimize the creation of a transient inflammatory niche that affords sustained exposure of CAR-T cells and cytokines. This facile approach yields increased CAR-T cell expansion, induces a more tumor-reactive CAR-T phenotype, and improves efficacy in treating solid tumors in mice.

Development of Cell-Carrying Magnetic Microrobots with Bioactive Nanostructured Titanate Surface for Enhanced Cell Adhesion

Cell-carrying magnet-driven microrobots are easily affected by blood flow or body fluids during transportation in the body, and thus cells often fall off from the microrobots. To reduce the loss of loaded cells, we developed a microrobot with a bioactive nanostructured titanate surface (NTS), which enhances cell adhesion. The microrobot was fabricated using 3D laser lithography and coated with nickel for magnetic actuation. Then, the microrobot was coated with titanium for the external generation of an NTS through reactions in NaOH solution. Enhanced cell adhesion may be attributed to the changes in the surface wettability of the microrobot and in the morphology of the loaded cells. An experiment was performed on a microfluidic chip for the simulation of blood flow environment, and result revealed that the cells adhered closely to the microrobot with NTS and were not obviously affected by flow. The cell viability and protein absorption test and alkaline phosphatase activity assay indicated that NTS can provide a regulatory means for improving cell proliferation and early osteogenic differentiation. This research provided a novel microrobotic platform that can positively influence the behaviour of cells loaded on microrobots through surface nanotopography, thereby opening up a new route for microrobot cell delivery.

The Potential Role of Nanoparticles as an Anticancer Therapy in the Treatment of Rectal Cancer

Nanotechnology is a rapidly developing science and is applied in a variety of diagnostic and treatment technologies. Colorectal cancer is one of the deadliest human diseases, and hence, wide research is underway regarding its preventative measures. This review demonstrated that “nano” drug delivery systems have successfully transferred pharmaceutical drug particles at the nanoscale as compared to larger particles. Research has shown a higher rate of disease progression among patients who receive conventional drugs compared to those who were given nanoscale drugs. However, the behavior of the cellular components differs from the performance of larger cellular components of the same type; these differences are due to the physical interactions between the nanoparticles (NPs). The review aimed to discuss several recent research studies focused on delivering NPs for the treatment of colorectal cancer (CRC). The reviewed experiments have primarily compared the use of NPs alone or with the addition of an anticancer drug or nanocarriers. These three research methods may help solve past problems and propose new future approaches for colorectal cancer by utilizing the available nanotechnologies. Furthermore, the review illustrated the underlying idea behind NP carriers and stem cell delivery that can be used to create a rapid delivery system for stem cells.

Biomaterials for microfluidic technology

Micro/nanomaterial-based drug and cell delivery systems play an important role in biomedical fields for their injectability and targeting. Microfluidics is a rapidly developing technology and has become a robust tool for preparing biomaterial micro/nanocarriers with precise structural control and high reproducibility. By flexibly designing microfluidic channels and manipulating fluid behavior, various forms of biomaterial carriers can be fabricated using microfluidics, including microspheres, nanoparticles and microfibers. In this review, recent advances in biomaterials for designing functional microfluidic vehicles are summarized. We introduce the application of natural materials such as polysaccharides and proteins as well as synthetic polymers in the production of microfluidic carriers. How the material properties determine the manufacture of carriers and the type of cargoes to be encapsulated is highlighted. Furthermore, the current limitations of microfluidic biomaterial carriers and perspectives on its future developments is presented.

Optimizing fibrin hydrogel toward effective neural progenitor cell delivery in spinal cord injury

Transplantation of neural progenitor cell (NPC) possessing the potential to differentiate into neurons may guard against spinal cord injury (SCI)- associated neuronal trauma. We propose that autologous-like NPC may reduce post-transplant immune response. The study used the rat SCI model to prove this concept. For isolation and expansion of rat NPC for cell-based SCI therapy, the in vitro protocol standardized with human NPC seemed suitable. The primary aim of this study is to select a cell/neural tissue-compatible biomaterial for improving NPC survival in vivo. The composition of the fibrin hydrogel is adjusted to obtain degradable, porous, and robust fibrin strands for supporting neural cell attachment, migration, and tissue regeneration. This study employed NPC culture to evaluate the cytocompatibility and suitability of the hydrogel, composed by adding graded concentrations of thrombin to a fixed fibrinogen concentration. The microstructure evaluation by scanning electron microscope guided the selection of a suitable composition for delivering the embedded cells. On adding more thrombin, fibrinogen clotted quickly but reduced porosity, pore size, and fiber strand thickness. The high activity of thrombin also affected NPC morphology and the in vitro cell survival. The selected hydrogel carried viable NPC and retained them at the injury site post-transplantation. The fibrin hydrogel played a protective role throughout the transfer process by providing cell attachment sites and survival signals. The fibrin and NPC together regulated the immune response at the SCI site reducing ED1+ve/ED2+ve macrophages in the early period of 8 to 16 days after injury. Migration of β-III tubulin+ve neural-like cells into the fibrin-injected control SCI is evident. The continuous use of a non-neurotoxic fibrin matrix could be a convenient strategy for in vitro NPC preparation, minimally invasive cell delivery, and better transplantation outcome.