New Therapy for Spinal Cord Injury: Autologous Genetically-Enriched Leucoconcentrate Integrated with Epidural Electrical Stimulation

The contemporary strategy for spinal cord injury (SCI) therapy aims to combine multiple approaches to control pathogenic mechanisms of neurodegeneration and stimulate neuroregeneration. In this study, a novel regenerative approach using an autologous leucoconcentrate enriched with transgenes encoding vascular endothelial growth factor (VEGF), glial cell line-derived neurotrophic factor (GDNF), and neural cell adhesion molecule (NCAM) combined with supra- and sub-lesional epidural electrical stimulation (EES) was tested on mini-pigs similar in morpho-physiological scale to humans. The complex analysis of the spinal cord recovery after a moderate contusion injury in treated mini-pigs compared to control animals revealed: better performance in behavioural and joint kinematics, restoration of electromyography characteristics, and improvement in selected immunohistology features related to cell survivability, synaptic protein expression, and glial reorganization above and below the injury. These results for the first time demonstrate the positive effect of intravenous infusion of autologous genetically-enriched leucoconcentrate producing recombinant molecules stimulating neuroregeneration combined with neuromodulation by translesional multisite EES on the restoration of the post-traumatic spinal cord in mini-pigs and suggest the high translational potential of this novel regenerative therapy for SCI patients.

Materials for Dentoalveolar Bioprinting: Current State of the Art

Although current treatments can successfully address a wide range of complications in the dentoalveolar region, they often still suffer from drawbacks and limitations, resulting in sub-optimal treatments for specific problems. In recent decades, significant progress has been made in the field of tissue engineering, aiming at restoring damaged tissues via a regenerative approach. Yet, the translation into a clinical product is still challenging. Novel technologies such as bioprinting have been developed to solve some of the shortcomings faced in traditional tissue engineering approaches. Using automated bioprinting techniques allows for precise placement of cells and biological molecules and for geometrical patient-specific design of produced biological scaffolds. Recently, bioprinting has also been introduced into the field of dentoalveolar tissue engineering. However, the choice of a suitable material to encapsulate cells in the development of so-called bioinks for bioprinting dentoalveolar tissues is still a challenge, considering the heterogeneity of these tissues and the range of properties they possess. This review, therefore, aims to provide an overview of the current state of the art by discussing the progress of the research on materials used for dentoalveolar bioprinting, highlighting the advantages and shortcomings of current approaches and considering opportunities for further research.

Newer Horizon of Mesenchymal Stem Cell–Based Therapy in the Management of SARS-CoV-2–Associated Mucormycosis: A Safe Hope for Future Medicine

SARS-CoV-2–infected patients are reported to show immunocompromised behavior that gives rise to a wide variety of complications due to impaired innate immune response, cytokine storm, and thrombo-inflammation. Prolonged use of steroids, diabetes mellitus, and diabetic ketoacidosis (DKA) are some of the factors responsible for the growth of Mucorales in such immunocompromised patients and, thus, can lead to a life-threatening condition referred to as mucormycosis. Therefore, an early diagnosis and cell-based management cosis is the need of the hour to help affected patients overcome this severe condition. In addition, extended exposure to antifungal drugs/therapeutics is found to initiate hormonal and neurological complications. More recently, mesenchymal stem cells (MSCs) have been used to exhibit immunomodulatory function and proven to be beneficial in a clinical cell-based regenerative approach. The immunomodulation ability of MSCs in mucormycosis patient boosts the immunity by the release of chemotactic proteins. MSC-based therapy in mucormycosis along with the combination of short-term antifungal drugs can be utilized as a prospective approach for mucormycosis treatment with promising outcomes. However, preclinical and in mucormyIn mucormycosis, the hyphae of clinical trials are needed to establish the precise mechanism of MSCs in mucormycosis treatment.

Perspective: Challenges Presented for Regeneration of Heterogeneous Musculoskeletal Tissues that Normally Develop in Unique Biomechanical Environments

Perspective: Musculoskeletal (MSK) tissues such as articular cartilage, menisci, tendons, and ligaments are often injured throughout life as a consequence of accidents. Joints can also become compromised due to the presence of inflammatory diseases such as rheumatoid arthritis. Thus, there is a need to develop regenerative approaches to address such injuries to heterogeneous tissues and ones that occur in heterogeneous environments. Such injuries can compromise both the biomechanical integrity and functional capability of these tissues. Thus, there are several challenges to overcome in order to enhance success of efforts to repair and regenerate damaged MSK tissues.Challenges: 1. MSK tissues arise during development in very different biological and biomechanical environments. These early tissues serve as a template to address the biomechanical requirements evolving during growth and maturation towards skeletal maturity. Many of these tissues are heterogeneous and have transition points in their matrix. The heterogeneity of environments thus presents a challenge to replicate with regard to both the cells and the ECM. 2. Growth and maturation of musculoskeletal tissues occurs in the presence of anabolic mediators such as growth hormone and the IGF-1 family of proteins which decline with age and are low when there is a greater need for the repair and regeneration of injured or damaged tissues with advancing age. Thus, there is the challenge of re-creating an anabolic environment to enhance incorporation of implanted constructs. 3. The environments associated with injury or chronic degeneration of tissues are often catabolic or inflammatory. Thus, there is the challenge of creating a more favorable in vivo environment to facilitate the successful implantation of in vitro engineered constructs to regenerate damaged tissues.Conclusions: The goal of regenerating MSK tissues has to be to meet not only the biological requirements (components and structure) but also the heterogeneity of function (biomechanics) in vivo. Furthermore, for many of these tissues, the regenerative approach has to overcome the site of injury being influenced by catabolism/inflammation. Attempts to date using both endogenous cells, exogenous cells and scaffolds of various types have been limited in achieving long term outcomes, but progress is being made.

Polymeric Hydrogel Scaffolds: Skin Tissue Engineering and Regeneration

Tissue engineering is a novel regenerative approach in the medicinal field that promises the regeneration of damaged tissues. Moreover, tissue engineering involves synthetic and natural biomaterials that facilitate tissue or organ growth outside the body. Not surprisingly, the demand for polymer-based therapeutical approaches in skin tissue defects has increased at an effective rate, despite the pressing clinical need. Among the 3D scaffolds for tissue engineering and regeneration approaches, hydrogel scaffolds have shown significant importance for their use as 3D cross-linked scaffolds in skin tissue regeneration due to their ideal moisture retention property and porosity biocompatibility, biodegradable, and biomimetic characteristics. In this review, we demonstrated the choice of ideal biomaterials to fabricate the novel hydrogel scaffolds for skin tissue engineering. After a short introduction to the bioactive and drug-loaded polymeric hydrogels, the discussion turns to fabrication and characterisation techniques of the polymeric hydrogel scaffolds. In conclusion, we discuss the excellent wound healing potential of stem cell-loaded hydrogels and Nano-based approaches to designing hydrogel scaffolds for skin tissue engineering.

A regenerative approach to the classification of the defects in the periodontal and alveolar ridge

The efficacy and long-term outcomes of the procedure of guided tissue regeneration depend on the basic morphometric condition of the defect and the choice of the technical supplement and the technical approach to surgery. Hystoarchitectonics of defects can be presented as a simplified four-parameter classification for use in clinical and expert practice in addition to making decisions in the regenerative surgery of defects in the periodontal and alveolar ridge.

One Planet Living and the legitimacy of sustainability governance: From standardised information to regenerative systems

The last two decades have seen the increased use and evolving forms of governance instruments seeking to promote sustainability across increasingly complex and varied contexts. These primarily voluntary instruments combine guidance on sustainability strategy and/or monitoring with marketable public information, such as certifications, ratings and reports, to incentivise take-up. Whilst they are typically based on standardised assessment criteria, recent academic literature emphasises more context-sensitive and systems-based, or ‘regenerative,’ approaches. We evaluate these differing approaches by adapting the concept of ‘legitimacy’, often applied to product certification, for this broader family of governance instruments. Prior research finds that standardised approaches have achieved success in take-up at the expense of other aspects of legitimacy, such as programme effectiveness and informational quality. Yet there remains a need for evaluation of established instruments based on a regenerative approach. We address this need through a focus on the One Planet Living framework established by Bioregional in the UK. Using practice-embedded, mixed-methods research, we identify achievements of the framework in terms of promoting effective, participatory and generally transparent programmes. Key limitations of the more bespoke approach concern take-up, resource requirements and the integration of measurement. Governance instruments for complex strategy and monitoring have, to date, struggled to combine programme effectiveness with scalability, suggesting there remains a need to develop more scalable regenerative approaches.

Human engineered heart tissue transplantation in a guinea pig chronic injury model

Myocardial injury leads to an irreversible loss of cardiomyocytes (CM). The implantation of human engineered heart tissue (EHT) has become a promising regenerative approach. Previous studies exhibited beneficial, dose-dependent effects of human induced pluripotent stem cell (hiPSC)-derived EHT patch transplantation in a guinea pig model in the subacute phase of myocardial injury. Yet, advanced heart failure often results from a chronic remodeling process. Therefore, from a clinical standpoint it is worthwhile to explore the ability to repair the chronically injured heart. In this study human EHT patches were generated from hiPSC-derived CM (15x10^6 cells) and implanted epicardially four weeks after injury in a guinea-pig cryo-injury model. Cardiac function was evaluated by echocardiography after a follow-up period of four weeks. Hearts revealed large transmural myocardial injuries amounting to 27% of the left ventricle. EHT recipient hearts demonstrated compact muscle islands of human origin in the scar region, as indicated by a positive staining for human Ku80 and dystrophin, remuscularizing 5% of the scar area. Echocardiographic analysis demonstrated no significant difference between animals that received EHT patches and animals in the control group. Thus, EHT patches engrafted in the chronically injured heart but in contrast to the subacute model, grafts were smaller and EHT patch transplantation did not improve left ventricular function, highlighting the difficulties for a regenerative approach.