Toward the emergence of nanoneurosurgery: part III--nanomedicine: targeted nanotherapy, nanosurgery, and progress toward the realization of nanoneurosurgery

The notion of nanotechnology has evolved since its inception as a fantastic conceptual idea to its current position as a mainstream research initiative with broad applications among all divisions of science. In the first part of this series, we reviewed the structures and principles that comprise the main body of knowledge of nanoscience and nanotechnology. In the second part, we discussed applications of nanotechnology to the emerging field of nanomedicine, with specific attention on medical diagnostics and imaging. This article further explores the applications of nanotechnology to nanomedicine. Specific attention is given to developments in therapeutic modalities, including advanced drug delivery systems and targeted nanotherapy, which will form the basis for the treatment arm of mature nanomedicine. A variety of modalities are discussed, including polymeric nanoparticles, micelles, liposomes, dendrimers, fullerenes, hydrogels, nanoshells, and smart surfaces. Applications of nanotechnology to nanosurgery and nanoneurosurgery are presented. Femtosecond laser systems, nanoneedles, and nanotweezers are presented as technologies that are operational at the nanoscale level and have the potential to revolutionize the practice of neurosurgery in a profound and momentous way.     

Nanotechnology and its relevance to the urologist

OBJECTIVES: We review important aspects of nanotechnology, and discuss the wide range of research and clinical applications of nanomedicine in the field of urology. There is particular emphasis on key clinical and pre-clinical studies to provide an update on recent and potential applications in the care of urological patients. METHODS: A directed Medline literature review of nanotechnology was performed. Important publications that have shaped our understanding of nanotechnology were selected for review and were augmented by manual searches of reference lists. RESULTS: Nanotechnology is the study, design, creation, synthesis, manipulation, and application of functional materials, devices, and systems through control of matter at the nanometer scale. Studies demonstrate a number of important concepts. These include nanovectors, nanotubes, and nanosensors for targeted drug delivery; nanowires and nanocantilever arrays for early detection of precancerous and malignant lesions; and nanopores for DNA sequencing. These advances will lead to significant applications relevant to the diagnosis, management, and treatment of all urological conditions. CONCLUSIONS: This review is designed for the urologist to provide an overview and update on nanotechnology and its applications in the field of urology. In the future, it is widely expected that nanotechnology and nanomedicine will have a significant impact on urological research and clinical practice, allowing urologists to intervene at the cellular and molecular level. With structured, safe implementation, nanotechnologies have the potential to revolutionise urological practice in our lifetime.     

Mechanizing medicine – Tomorrows history started yesterday

History is by nature a retrospective subject, there usually being an interval between any event, a review or impact of the subject being considered. This NPSA Historian’s paper, takes a long and quick historical view of influences that fostered changes resulting in the current state of affairs in the field of medicine and medical care. The fields of medicine and surgery, are undergoing rapid changes as a result of technological and other advances that are making tomorrow’s medical history seemingly happening yesterday. Prospectively, the impact of current change and its rapidity has the potential to radically change the future practice of the art and craft of our profession.     

New frontiers in nanotechnology for cancer treatment

Nanotechnology is a field of research at the crossroads of biology, chemistry, physics, engineering, and medicine. Design of multifunctional nanoparticles capable of targeting cancer cells, delivering and releasing drugs in a regulated manner, and detecting cancer cells with enormous specificity and sensitivity are just some examples of the potential application of nanotechnology to oncological diseases. In this review we discuss the recent advances of cancer nanotechnology with particular attention to nanoparticle systems that are in clinical practice or in various stages of development for cancer imaging and therapy.     

Laparoscopic nephrectomy using the EnSeal Tissue Sealing and Hemostasis System: successful therapeutic application of nanotechnology.

The potential impact of nanotechnology in the field of urology is broad with diagnostic and therapeutic benefits that have only recently begun to be explored. Application of nanotechnology principles to tissue and vessel sealing during laparoscopic procedures may reduce associated thermal injury and inflammatory response. We report our initial experience using the EnSeal Tissue Sealing and Hemostasis System during laparoscopic nephrectomy and discuss its potential advantages and disadvantages compared with those of contemporary technologies.     

Toward the emergence of nanoneurosurgery: part II--nanomedicine: diagnostics and imaging at the nanoscale level

THE NOTION OF nanotechnology has evolved since its inception as a fantastic conceptual idea to its current position as a mainstream research initiative with broad applications among all divisions of science. In the first part of this series, we reviewed the structures and principles that comprise the main body of knowledge of nanoscience and nanotechnology (58). This article reviews and discusses the applications of nanotechnology to biological systems that will undoubtedly transform the foundations of disease diagnosis, treatment, and prevention in the future. Specific attention is given to developments in diagnostics and imaging at the nanoscale level. The use of nanoparticles and nanomaterials as biodetection agents for deoxyribonucleic acid and proteins is presented. In addition, nanodevices, such as nanowires, nanotubes, and nanocantilevers, can be combined with nanoarrays and nanofluidics to create integrated and automated nanodetection platforms. Molecular imaging modalities based on quantum dots and magnetic nanoparticles are also discussed. This technology has been extended to the imaging of intracranial neoplasms. Further innovation within these disciplines will form the basis for the development of mature nanomedicine. The final article of the series will focus on additional advancements in nanomedicine, namely nanotherapy and nanosurgery, and will cover the innovations that will lead to the eventual realization of nanoneurosurgery.     

Regenerative medicine as applied to general surgery

The present review illustrates the state of the art of regenerative medicine (RM) as applied to surgical diseases and demonstrates that this field has the potential to address some of the unmet needs in surgery. RM is a multidisciplinary field whose purpose is to regenerate in vivo or ex vivo human cells, tissues, or organs to restore or establish normal function through exploitation of the potential to regenerate, which is intrinsic to human cells, tissues, and organs. RM uses cells and/or specially designed biomaterials to reach its goals and RM-based therapies are already in use in several clinical trials in most fields of surgery. The main challenges for investigators are threefold: Creation of an appropriate microenvironment ex vivo that is able to sustain cell physiology and function in order to generate the desired cells or body parts; identification and appropriate manipulation of cells that have the potential to generate parenchymal, stromal and vascular components on demand, both in vivo and ex vivo; and production of smart materials that are able to drive cell fate.     

Emerging technologies in organ preservation,tissue engineering and regenerative medicine: a blessing or curse for transplantation?

Since the beginning of transplant medicine in the 1950s, advances in surgical technique and immunosuppressive therapy have created the success story of modern organ transplantation. However, today more than ever, we are facing a huge discrepancy between organ supply and demand, limiting the potential for transplantation to save and improve the lives of millions. To address the current limitations and shortcomings, a variety of emerging new technologies focusing on either maximizing the availability of organs or on generating new organs and organ sources hold great potential to eventully overcoming these hurdles. These advances are mainly in the field of regenerative medicine and tissue engineering. This review gives an overview of this emerging field and its multiple sub‐disciplines and highlights recent advances and existing limitations for widespread clinical application and potential impact on the future of transplantation.     

Nanomedizin

Nanomedicine is the application of nanotechnology to the medical field. Nanotechnology deals with structures in the range of 1–100 nm and focuses on the development of materials with novel properties. As a result it is considered as a key technology of the twenty-first century and promises to deliver innovative methods to medicine in general and to surgery in particular. Clinical studies will deal with nanotechnology-based cancer treatment and innovative nanocontainers for targeted drug delivery and more efficient treatment. Nanotechnology will start a new era in medicine which will offer sophisticated methods for diagnosis, therapy and prevention. These tools will be a challenge to efficient education and training of surgeons.     

Nanobiotechnology and bone regeneration: a mini-review

The purpose of this paper is to review current developments in bone tissue engineering, with special focus on the promising role of nanobiotechnology. This unique fusion between nanotechnology and biotechnology offers unprecedented possibilities in studying and modulating biological processes on a molecular and atomic scale. First we discuss the multiscale hierarchical structure of bone and its implication on the design of new scaffolds and delivery systems. Then we briefly present different types of nanostructured scaffolds, and finally we conclude with nanoparticle delivery systems and their potential use in promoting bone regeneration. This review is not meant to be exhaustive and comprehensive, but aims to highlight concepts and key advances in the field of nanobiotechnology and bone regeneration.     

Looking forward

With the rapid acceleration of technology, fundamental changes in the science of surgery are emerging within the lifetime of a surgeon's practice. This review includes the technologies of information systems, robotics, virtual reality, simulation and training, directed-energy surgical instruments, photonics, and brain chips, as well as their impact on the practice of surgery. Also considered are those technologies that may replace surgery, such as genetic engineering, tissue engineering, suspended animation, and nanotechnology. The evidence for each of these technologies is presented as preliminary reports of their success in research laboratories.     

Nanotechnology applications in urology: a review

The objectives of this review are to discuss the current literature and summarise some of the promising areas with which nanotechnology may improve urological care. A Medline literature search was performed to elucidate all relevant studies of nanotechnology with specific attention to its application in urology. Urological applications of nanotechnology include its use in medical imaging, gene therapy, drug delivery, and photothermal ablation of tumours. In vitro and animal studies have shown initial encouraging results. Further study of nanotechnology for urological applications is warranted to bridge the gap between preclinical studies and translation into clinical practice, but nanomedicine has shown significant potential to improve urological patient care.     

Nanotechnology: the scope and potential applications in orthopedic surgery

Nanotechnology involves manipulation of matter measuring 1–100 nm in at least one of its dimensions at the molecular level. Engineering and manipulation of matter at the molecular level has several advantages in the field of medicine (nanomedicine) since most of the biological molecules exist and function at a nanoscale. Though promising, questions still remain on how much of this will ultimately translate into achieving better patient care. Concerns of cost-effectiveness and nanotechnology safety still remain unclear. Orthopedics is an attractive area for the application of nanotechnology since the bone, and its constituents such as hydroxyapatite, Haversian systems, and the collagen fibrils are nanocompounds. The major orthopedic applications of nanotechnology involve around (i) effective drug delivery systems for antibiotics and chemotherapeutic agents, (ii) surface preparation of implants and prosthesis to improve osteointegration and reduce biofilm formation, (iii) controlled drug eluting systems to combat implant-related infections, (iv) tissue engineering for scaffolds preparation to deal with bone and cartilage defects, and (v) diagnostic applications in the field of oncology and musculoskeletal infections.     

Can colonoscopy diagnose transmural ischaemic colitis after abdominal aortic surgery? An evidence-based approach.

OBJECTIVES: to assess the diagnostic value of colonoscopy in ischaemic colitis following abdominal aortic surgery, based on a literature review, and to introduce the concept of evidence-based medicine. METHOD: a review of the literature according to evidence-based principles was made by all doctors of our department. RESULTS: seven prospective non-randomised reports on routine colonoscopy after abdominal aortic surgery were found. None of the participants found all the reports, and the last was identified by the reviewer. CONCLUSIONS: Endoscopy may disclose ischaemic colitis, but cannot separate transmural from the clinically less important mucosal ischaemia. Endoscopy had no impact on mortality in any of the prospective series. The evidence-based conference was an inspiring teaching modality, and illustrated for the participants the difficulty in performing a targeted literature search.     

Neurosurgery in the realm of 10(-9), part 1: stardust and nanotechnology in neuroscience

Nanotechnology as a science has evolved from notions and speculation to emerge as a prominent combination of science and engineering that stands to impact innumerable aspects of technology. Medicine in general and neurosurgery in particular will benefit greatly in terms of improved diagnostic and therapeutic capabilities. The recent explosion in nanotechnology products, including diverse applications such as beauty products and medical contrast agents, has been accompanied by an ever increasing volume of literature. Recent articles from our institution provided an historical and scientific background of nanotechnology, with a purposeful focus on nanomedicine. Future applications of nanotechnology to neuroscience and neurosurgery were briefly addressed. The present article is the first of two that will further this discussion by providing specific details of current nanotechnology applications and research related to neuroscience and clinical neurosurgery. This article also provides relevant perspective in scale, history, economics, and toxicology. Topics of specific importance to developments or advances of technologies used by neuroscientists and neurosurgeons are presented. In addition, advances in the field of microelectromechanical systems technology are discussed. Although larger than nanoscale, microelectromechanical systems technologies will play an important role in the future of medicine and neurosurgery. The second article will discuss current nanotechnologies that are being, or will be in the near future, incorporated into the armamentarium of the neurosurgeon. The goal of these articles is to keep the neuroscience community abreast of current developments in nanotechnology, nanomedicine, and, in particular, nanoneurosurgery, and to present possibilities for future applications of nanotechnology. As applications of nanotechnology permeate all forms of scientific and medical research, clinical applications will continue to emerge. Physicians of the present and future must take an active role in shaping the design and research of nanotechnologies to ensure maximal clinical relevance and patient benefit.     

Small-volume resuscitation: from experimental evidence to clinical routine. Advantages and disadvantages of hypertonic solutions

BACKGROUND: The concept of small-volume resuscitation (SVR) using hypertonic solutions encompasses the rapid infusion of a small dose (4 ml per kg body weight, i.e. approximately 250 ml in an adult patient) of 7.2-7.5% NaCl/colloid solution. Originally, SVR was aimed for initial therapy of severe hypovolemia and shock associated with trauma. METHODS: The present review focuses on the findings concerning the working mechanisms responsible for the rapid onset of the circulatory effect, the impact of the colloid component on microcirculatory resuscitation, and describes the indications for its application in the preclinical scenario as well as perioperatively and in intensive care medicine. RESULTS: With respect to the actual data base of clinical trials SVR seems to be superior to conventional volume therapy with regard to faster normalization of microvascular perfusion during shock phases and early resumption of organ function. Particularly patients with head trauma in association with systemic hypotension appear to benefit. Besides, potential indications for this concept include cardiac and cardiovascular surgery (attenuation of reperfusion injury during declamping phase) and burn injury. The review also describes disadvantages and potential adverse effects of SVR: CONCLUSION: Small-volume resuscitation by means of hypertonic NaCl/colloid solutions stands for one of the most innovative concepts for primary resuscitation from trauma and shock established in the past decade. Today the spectrum of potential indications involves not only prehospital trauma care, but also perioperative and intensive care therapy.     

Designer genes: Filling the gap in transplantation

Accelerated evolution of the field of functional genomics has been greatly facilitated by high-throughput microarray-based gene function studies, relating to the parallel and serial expression measurements of genomes. Microarray experimentation is being applied for the study of basic research questions, drug target discovery, pharmacology, toxicogenomics, target selectivity, disease biomarker determination, development of prognostic tests, and disease subclass determination. This article will review the current applications of microarray technology in the field of organ transplantation and discuss the potential impact of this technology on transplantation medicine.     

Introduction to nanotechnology and its applications to medicine

Nanotechnology can be defined as the science and engineering involved in the design, synthesis, characterization, and application of materials and devices whose smallest functional organization in at least one dimension is on the nanometer scale or one billionth of a meter. At these scales, consideration of individual molecules and interacting groups of molecules in relation to the bulk macroscopic properties of the material or device becomes important, since it is control over the fundamental molecular structure that allows control over the macroscopic chemical and physical properties. Applications to medicine and physiology imply materials and devices designed to interact with the body at subcellular (i.e., molecular) scales with a high degree of specificity. This can potentially translate into targeted cellular and tissue-specific clinical applications designed to achieve maximal therapeutic affects with minimal side effects. In this review the main scientific and technical aspects of nanotechnology are introduced and some of its potential clinical applications are discussed.