Enhancing regenerative medicine with self-healing hydrogels: A solution for tissue repair and advanced cyborganic healthcare devices.

Considering the global burden related to tissue and organ injuries or failures, self-healing hydrogels may be an attractive therapeutic alternative for the future. Self-healing hydrogels are highly hydrated 3D structures with the ability to self-heal after breaking, this property is attributable to a variety of dynamic non-covalent and covalent bonds that are able to re-linking within the matrix. Self-healing ability specially benefits minimal invasive medical treatments with cell-delivery support. Moreover, those tissue-engineered self-healing hydrogels network have demonstrated effectiveness for myriad purposes; for instance, they could act as delivery-platforms for different cargos (drugs, growth factors, cells, among others) in tissues such as bone, cartilage, nerve or skin. Besides, self-healing hydrogels have currently found their way into new and novel applications; for example, with the development of the self-healing adhesive hydrogels, by merely aiding surgical closing processes and by providing biomaterial-tissue adhesion. Furthermore, conductive hydrogels permit the stimuli and monitoring of natural electrical signals, which facilitated a better fitting of hydrogels in native tissue or the diagnosis of various health diseases. Lastly, self-healing hydrogels could be part of cyborganics - a merge between biology and machinery - which can pave the way to a finer healthcare devices for diagnostics and precision therapies.

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.

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.

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.

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.

Nanoclay Reinforced Biomaterials for Mending Musculoskeletal Tissue Disorders.

Nanoclay-reinforced biomaterials have sparked a new avenue in advanced healthcare materials that can potentially revolutionize treatment of musculoskeletal defects. Native tissues display many important chemical, mechanical, biological, and physical properties that engineered biomaterials need to mimic for optimal tissue integration and regeneration. However, it is time-consuming and difficult to endow such combinatorial properties on materials via feasible and nontoxic procedures. Fortunately, a number of nanomaterials such as graphene, carbon nanotubes, MXenes, and nanoclays already display a plethora of material properties that can be transferred to biomaterials through a simple incorporation procedure. In this direction, the members of the nanoclay family are easy to functionalize chemically, they can significantly reinforce the mechanical performance of biomaterials, and can provide bioactive properties by ionic dissolution products to upregulate cartilage and bone tissue formation. For this reason, nanoclays can become a key component for future orthopedic biomaterials. In this review, we specifically focus on the rapidly decreasing gap between clinic and laboratory by highlighting their application in a number of promising in vivo studies.

Hacking Human Beings with Machine Biology to Increase Lifespan.

Imagine a world where machines can program cells to deliver therapeutics in a remote-controlled, time-specific, and targeted manner. Or, what if physicians could collect data continuously to establish intimate links between therapy and disease progression? Such machine biology systems could empower physicians beyond imagination and give rise to personalized treatments.

Antipsychotics and pituitary tumors: an analysis of the European pharmacovigilance database (EudraVigilance).

One of the possible long-term consequences of antipsychotic-induced hyperprolactinemia is the development of pituitary tumors - prolactinomas. So far, two pharmacovigilance studies of spontaneous adverse event report databases have suggested an increased risk, whereas a longitudinal study carried out with risperidone showed no evidence of increased risk of tumors with mass effect. Besides, information on amisulpride and paliperidone is lacking. Thus, in this study, we aimed to analyze the European pharmacovigilance database (EudraVigilance) to shed light on this issue. We searched for all suspected spontaneous cases of pituitary tumors associated with antipsychotics in EudraVigilance up to 23 March 2017. To assess the association between pituitary tumor cases and each antipsychotic, we calculated the proportional reporting ratios. Among 4 964 866 events of all types recorded in EudraVigilance, we found 292 cases of pituitary tumors associated with antipsychotics. All atypical antipsychotics except clozapine fulfilled the criteria to generate a safety signal. The highest proportional reporting ratio values were found for amisulpride 51.57 (36.3-73.2), risperidone 21.83 (18.4-25.8), and paliperidone 19.95 (14.7-27.1). Sulpiride and haloperidol showed a higher risk among typical antipsychotics 12.4 (5.89-26.1) and 7.0 (4.35-11.3). Notably, we found that a mass effect was present in 16% of the cases. Besides, 18 cases occurred in patients aged below 18 years. Our analysis of the data in EudraVigilance confirms the safety signal detected by previous studies. Interestingly, for the first time, we show that the association seems to be the strongest for amisulpride and that a mass effect was present in around 16% of the cases.

Advances in stem cell therapy for cartilage regeneration in osteoarthritis.

INTRODUCTION: Osteoarthritis (OA) is a progressive joint disease that compromises the structural integrity of cartilage tissue. Conventional treatments based on medication or surgery are nowadays inefficient and cell-based therapy has emerged as one of the most promising methods for cartilage regeneration. The first therapy developed for cartilage defects was autologous chondrocyte implantation, but in the last few decades stem cells (SCs) from different sources have been proposed as a possible alternative for OA. AREAS COVERED: SC sources and available delivery procedures (scaffolds/hydrogels) are presented, along with the main issues arisen in this regard. Thereafter, preclinical and clinical trials performed in recent years are reviewed in order to take a glance toward the potential benefits that such therapies could deliver to the patients. EXPERT OPINION: SCs have proven their potential and safety for OA treatment. Nevertheless, there are still many questions to be resolved before their widespread used in clinical practice, such as the treatment mechanism, the best cell source, the most appropriate processing method, the most effective dose and delivery procedure, and their efficacy. In this sense, long-term follow-up and larger randomized controlled trials utilizing standardized and established outcome scores are mandatory to make objective conclusions.