Current trends in viral gene therapy for human orthopaedic regenerative medicine

[Abstract] Background: Viral vector-based therapeutic gene therapy is a potent strategy to enhance the intrinsic reparative abilities of human orthopaedic tissues. However, clinical application of viral gene transfer remains hindered by detrimental responses in the host against such vectors (immunogenic responses, vector dissemination to nontarget locations). Combining viral gene therapy techniques with tissue engineering procedures may offer strong tools to improve the current systems for applications in vivo. Methods: The goal of this work is to provide an overview of the most recent systems exploiting biomaterial technologies and therapeutic viral gene transfer in human orthopaedic regenerative medicine. Results: Integration of tissue engineering platforms with viral gene vectors is an active area of research in orthopaedics as a means to overcome the obstacles precluding effective viral gene therapy. Conclusions: In light of promising preclinical data that may rapidly expand in a close future, biomaterial-guided viral gene therapy has a strong potential for translation in the field of human orthopaedic regenerative medicine

Systems for the Functional Evaluation of Human Heart Tissues Derived from Pluripotent Stem Cells

Human pluripotent stem cells (hPSCs) are expected to be a promising cell source in regenerative medicine and drug discovery for the treatment of various intractable diseases. An approach for creating a 3-dimensional (3D) structure from hPSCs that mimics human cardiac tissue functions has made it theoretically possible to conduct drug discovery and cardiotoxicity tests by assessing pharmacological responses in human cardiac tissues by a screening system using a compound library. The myocardium functions as a tissue composed of organized vascular networks, supporting stromal cells and cardiac muscle cells. Considering this, the reconstruction of tissue structure by various cells of cardiovascular lineages, such as vascular cells and cardiac muscle cells, is desirable for the ideal conformation of hPSC-derived cardiac tissues. Heart-on-a-chip, an organ-on-a-chip system to evaluate the physiological pump function of 3D cardiac tissues might hold promise in medical researchs such as drug discovery and regenerative medicine. Here, we review various modalities to evaluate the function of human stem cell-derived cardiac tissues and introduce heart-on-a-chip systems that can recapitulate physiological parameters of hPSC-derived cardiac tissues

Analysis of Power Absorption by Human Tissue in Deeply Implantable Medical Sensor Transponders

The use of sensor transponder systems in medicine opens valuable possibilities in therapy and diagnostics. This chapter is about physical effects by the use of sensor transponder technology for medicine applications, especially for deeply implanted passive powered sensor transponders. This chapter will inform about present and future applications. The influence of human body on the energy transmission in a sensor transponder system is shown. The dielectrical properties of human tissue are discussed. A way how to estimate losses in an analytical way and with the use of a 3D FTDT method is presented. Finally, a design example of an energy transmission for a sensor transponder is shown with a calculation of the optimal frequency and experimental results

Advances in 3D Organoid Models for Stem Cell-Based Cardiac Regeneration

The adult human heart cannot regain complete cardiac function following tissue injury, making cardiac regeneration a current clinical unmet need. There are a number of clinical procedures aimed at reducing ischemic damage following injury; however, it has not yet been possible to stimulate adult cardiomyocytes to recover and proliferate. The emergence of pluripotent stem cell technologies and 3D culture systems has revolutionized the field. Specifically, 3D culture systems have enhanced precision medicine through obtaining a more accurate human microenvironmental condition to model disease and/or drug interactions in vitro. In this study, we cover current advances and limitations in stem cell-based cardiac regenerative medicine. Specifically, we discuss the clinical implementation and limitations of stem cell-based technologies and ongoing clinical trials. We then address the advent of 3D culture systems to produce cardiac organoids that may better represent the human heart microenvironment for disease modeling and genetic screening. Finally, we delve into the insights gained from cardiac organoids in relation to cardiac regeneration and further discuss the implications for clinical translation

Epilepsy at Every Angle: A Systems Biology Approach to a Cure

Caused by birth trauma, malformation, stroke, brain tumor or head injury and affecting as much as 1 percent of the population, epilepsy is one of the least understood human disorders in the most complicated of organs – the brain. Groundbreaking work to unlock the disease’s cure is in motion in the lab of Jeffrey Loeb, M.D., Ph.D., associate professor of neurology, member of the WSU/DMC Comprehensive Epilepsy Program and associate director of the Center for Molecular Medicine and Genetics in the School of Medicine. By applying a systems biology approach to the study of human epileptic brain tissue, Loeb and his team are working to identify a “final common pathway” of genes consistently induced at human epileptic foci. Using this pathway as a drug target, Loeb and his team will work to develop drugs that successfully prevent epilepsy, first in rats, then in humans

Magnetic-responsive hydrogels for cartilage tissue engineering

Publicado em "Journal of Tissue Engineering and Regenerative Medicine", vol. 7, supp. 1 (2013)The use of magnetic nanoparticles (MNPs) has been explored as an alternative approach to overcome current limitations of regenerative medicine strategies. Cell engineering approaches where MNPs are incorporated within three-dimensional constructs, such as scaffolds or hydrogels may constitute a novel and attractive approach towards the development of a magnetically-responsive system. These systems would enable remote controlled actions over tissue engineered constructs in vitro and in vivo. Moreover, growing evidence suggests that the application of a magnetic field may enhance biological performance over commonly used static culture conditions providing stimulation for cell proliferation, migration and differentiation. In this work we analyze the role of magnetic stimulation on the behavior of human adipose derived stem cells (hASCs) laden in k-carrageenan hydrogels aiming at cartilage tissue engineering approaches. Thermo-responsive natural-based κ-carrageenan hydrogels were used as 3D templates since previous studies(1) report the adequate environment provided by these materials to support the viability and chondrogenic differentiation of several types of cells

The real-time molecular characterisation of human brain tumours during surgery using Rapid Evaporative Ionization Mass Spectrometry [REIMS] and Raman spectroscopy: a platform for precision medicine in neurosurgery

Aim: To investigate new methods for the chemical detection of tumour tissue during neurosurgery. Rationale: Surgeons operating on brain tumours currently lack the ability to directly and immediately assess the presence of tumour tissue to help guide resection. Through developing a first in human application of new technology we hope to demonstrate the proof of concept that chemical detection of tumour tissue is possible. It will be further demonstrated that information can be obtained to potentially aid treatment decisions. This new technology could, therefore, become a platform for more effective surgery and introducing precision medicine to Neurosurgery. Methods: Molecular analysis was performed using Raman spectroscopy and Rapid Evaporative Ionization Mass Spectrometry (REIMS). These systems were first developed for use in brain surgery. A single centre prospective observational study of both modalities was designed involving a total of 75 patients undergoing craniotomy and resection of a range of brain tumours. A neuronavigation system was used to register spectral readings in 3D space. Precise intraoperative readings from different tumour zones were taken and compared to matched core biopsy samples verified by routine histopathology. Results: Multivariate statistics including PCA/LDA analysis was used to analyse the spectra obtained and compare these to the histological data. The systems identified normal versus tumour tissue, tumour grade, tumour type, tumour density and tissue status of key markers of gliomagenesis. Conclusions: The work in this thesis provides proof of concept that useful real time intraoperative spectroscopy is possible. It can integrate well with the current operating room setup to provide key information which could potentially enhance surgical safety and effectiveness in increasing extent of resection. The ability to group tissue samples with respect to genomic data opens up the possibility of using this information during surgery to speed up treatment, escalate/deescalate surgery in specific phenotypic groups to introduce precision medicine to Neurosurgery.Open Acces

Nanotechnology in regenerative medicine: the materials side

Regenerative medicine is an emerging multidisciplinary field that aims to restore, maintain or enhance tissues and hence organ functions. Regeneration of tissues can be achieved by the combination of living cells, which will provide biological functionality, and materials, which act as scaffolds to support cell proliferation. Mammalian cells behave in vivo in response to the biological signals they receive from the surrounding environment, which is structured by nanometre-scaled components. Therefore, materials used in repairing the human body have to reproduce the correct signals that guide the cellstowards a desirable behaviour. Nanotechnology is not only an excellent tool to produce material structures that mimic the biological ones but also holds the promise of providing efficient delivery systems. The application of nanotechnology to regenerative medicine is a wide issue and this short review will only focus on aspects of nanotechnology relevant to biomaterials science. Specifically, the fabrication of materials, such as nanoparticles and scaffolds for tissue engineering, and the nanopatterning of surfaces aimed at eliciting specific biological responses from the host tissue will be addressed.Postprint (published version

Role of Iron Oxide (Fe2O3) Nanocomposites in Advanced Biomedical Applications: A State-of-the-Art Review

Nanomaterials have demonstrated a wide range of applications and recently, novel biomedical studies are devoted to improving the functionality and effectivity of traditional and unmodified systems, either drug carriers and common scaffolds for tissue engineering or advanced hydrogels for wound healing purposes. In this regard, metal oxide nanoparticles show great potential as versatile tools in biomedical science. In particular, iron oxide nanoparticles with different shape and sizes hold outstanding physiochemical characteristics, such as high specific area and porous structure that make them idoneous nanomaterials to be used in diverse aspects of medicine and biological systems. Moreover, due to the high thermal stability and mechanical strength of Fe2O3, they have been combined with several polymers and employed for various nano-treatments for specific human diseases. This review is focused on summarizing the applications of Fe2O3-based nanocomposites in the biomedical field, including nanocarriers for drug delivery, tissue engineering, and wound healing. Additionally, their structure, magnetic properties, biocompatibility, and toxicity will be discussed