Nanomaterial-based drug delivery of immunomodulatory factors for bone and cartilage tissue engineering.

As life expectancy continues to increase, so do disorders related to the musculoskeletal system. Orthopedics-related impairments remain a challenge, with nearly 325 thousand and 120 thousand deaths recorded in 2019. Musculoskeletal system, including bone and cartilage tissue, is a living system in which cells constantly interact with the immune system, which plays a key role in the tissue repair process. An alternative to bridge the gap between these two systems is exploiting nanomaterials, as they have proven to serve as delivery agents of an array of molecules, including immunomodulatory agents (anti-inflammatory drugs, cytokines), as well as having the ability to mimic tissue by their nanoscopic structure and promote tissue repair per se. Therefore, this review outlooks nanomaterials and immunomodulatory factors widely employed in the area of bone and cartilage tissue engineering. Emerging developments in nanomaterials for delivery of immunomodulatory agents for bone and cartilage tissue engineering applications have also been discussed. It can be concluded that latest progress in nanotechnology have enabled to design intricate systems with the ability to deliver biologically active agents, promoting tissue repair and regeneration; thus, nanomaterials studied herein have shown great potential to serve as immunomodulatory agents in the area of tissue engineering.

Sumecton reinforced gelatin-based scaffolds for cell-free bone regeneration.

Bone tissue engineering has risen to tackle the challenges of the current clinical need concerning bone fractures that is already considered a healthcare system problem. Scaffold systems for the repair of this tissue have yielded different combinations including biomaterials with nanotechnology or biological agents. Herein, three-dimensional porous hydrogels were engineered based on gelatin as a natural biomaterial and reinforced with synthetic saponite nanoclays. Scaffolds were biocompatible and shown to enhance the inherent properties of pristine ones, in particular, proved to withstand pressures similar to load-bearing tissues. Studies with murine mesenchymal stem cells found that scaffolds had the potential to proliferate and promote cell differentiation. In vivo experiments were conducted to gain insight about the ability of these cell-free scaffolds to regenerate bone, as well as to determine the role that these nanoparticles in the scaffold could play as a drug delivery system. SDF-1 loaded scaffolds showed the highest percentage of bone formation, which was corroborated by osteogenic markers and new blood vessels. Albeit a first attempt in the field of synthetic nanosilicates, these results suggest that the designed constructs may serve as delivery platforms for biomimetic agents to mend bony defects, circumventing high doses of therapeutics and cell-loading systems.

Progress in self-healing hydrogels and their applications in bone tissue engineering.

Bone tissue engineering (BTE) is constantly seeking novel treatments to address bone injuries in all their varieties. It is necessary to find new ways to create structures that perfectly emulate the native tissue. Self-healing hydrogels have been a breakthrough in this regard, as they are able to reconstitute their links after they have been partially broken. Among the most outstanding biomaterials when it comes to developing these hydrogels for BTE, those polymers of natural origin (e.g., gelatin, alginate) stand out, although synthetics such as PEG or nanomaterials like laponite are also key for this purpose. Self-healing hydrogels have proven to be efficient in healing bone, but have also played a key role as delivery-platforms for drugs or other biological agents. Moreover, some researchers have identified novel uses for these gels as bone fixators or implant coatings. Here, we review the progress of self-healing hydrogels, which hold great promise in the field of tissue engineering.

Nanoclay-reinforced HA/alginate scaffolds as cell carriers and SDF-1 delivery-platforms for bone tissue engineering.

Bone tissue engineering has come on the scene to overcome the difficulties of the current treatment strategies. By combining biomaterials, active agents and growth factors, cells and nanomaterials, tissue engineering makes it possible to create new structures that enhance bone regeneration. Herein, hyaluronic acid and alginate were used to create biologically active hydrogels, and montmorillonite nanoclay was used to reinforce and stabilize them. The developed scaffolds were found to be biocompatible and osteogenic with mMSCs in vitro, especially those reinforced with the nanoclay, and allowed mineralization even in the absence of differentiation media. Moreover, an in vivo investigation was performed to establish the potential of the hydrogels to mend bone and act as cell-carriers and delivery platforms for SDF-1. Scaffolds embedded with SDF-1 exhibited the highest percentages of bone regeneration as well as of angiogenesis, which confirms the suitability of the scaffolds for bone. Although there are a number of obstacles to triumph over, these bioengineered structures showed potential as future bone regeneration treatments.

Progress in Gelatin as Biomaterial for Tissue Engineering.

Tissue engineering has become a medical alternative in this society with an ever-increasing lifespan. Advances in the areas of technology and biomaterials have facilitated the use of engineered constructs for medical issues. This review discusses on-going concerns and the latest developments in a widely employed biomaterial in the field of tissue engineering: gelatin. Emerging techniques including 3D bioprinting and gelatin functionalization have demonstrated better mimicking of native tissue by reinforcing gelatin-based systems, among others. This breakthrough facilitates, on the one hand, the manufacturing process when it comes to practicality and cost-effectiveness, which plays a key role in the transition towards clinical application. On the other hand, it can be concluded that gelatin could be considered as one of the promising biomaterials in future trends, in which the focus might be on the detection and diagnosis of diseases rather than treatment.

Composite alginate-gelatin hydrogels incorporating PRGF enhance human dental pulp cell adhesion, chemotaxis and proliferation.

The increasing prevalence of tissue injuries is fueling the development of autologous biological treatments for regenerative medicine. Here, we investigated the potential of three different bioinks based on the combination of gelatin and alginate (GA), enriched in either hydroxyapatite (GAHA) or hydroxyapatite and PRGF (GAHAP), as a favorable microenvironment for human dental pulp stem cells (DPSCs). Swelling behaviour, in vitro degradation and mechanical properties of the matrices were evaluated. Morphological and elemental analysis of the scaffolds were also performed along with cytocompatibility studies. The in vitro cell response to the different scaffolds was also assessed. Results showed that all scaffolds presented high swelling capacity, and those that contained HA showed higher Young's modulus. GAHAP had the lowest degradation rate and the highest values of cytocompatibility. Cell adhesion and chemotaxis were significantly increased when PRGF was incorporated to the matrices. GAHA and GAHAP compositions promoted the highest proliferative rate as well as significantly stimulated osteogenic differentiation. In conclusion, the enrichment with PRGF improves the regenerative properties of the composites favouring the development of personalized constructs.

Emerging strategies for beta cell transplantation to treat diabetes.

Beta cell replacement has emerged as an attractive therapeutic alternative to traditional exogenous insulin administration for management of type 1 diabetes (T1D). Beta cells deliver insulin dynamically based on individual glycometabolic requirements, providing glycemic control while significantly reducing patient burden. Although transplantation into the portal circulation is clinically available, poor engraftment, low cell survival, and immune rejection have sparked investigation of alternative strategies for beta cell transplantation. In this review, we focus on current micro- and macroencapsulation technologies for beta cell transplantation and evaluate their advantages and challenges. Specifically, we comment on recent methods to ameliorate graft hypoxia including enhanced vascularization, reduction of pericapsular fibrotic overgrowth (PFO), and oxygen supplementation. We also discuss emerging beta cell-sourcing strategies to overcome donor shortage and provide insight into potential approaches to address outstanding challenges in the field.