Bioengineers

Bioengineers play a critical role in both diagnostics and treatment intervention thanks to their ability to design and develop devices and technologies that can be implemented into the clinic to ensure cancers are diagnosed at their early onset and that cancer patients are offered the best suited and most effective treatment.

From: Bioengineering Innovative Solutions for Cancer , 2020

Bioengineering

Philip Kosky , ... George Wise , in Exploring Engineering (Fifth Edition), 2021

16.2 What Bioengineers Do

Bioengineers have a wide variety of career choices. Some work alongside medical practitioners, developing new medical techniques, medical devices, and instrumentation for manufacturing companies. Hospitals and clinics employ clinical engineers to maintain and improve the technological support systems used for patient care. Engineers with advanced bioengineering degrees can perform biological and medical research in educational and government research laboratories.

Many bioengineers help people by solving complex problems in medicine and health care. Some bioengineering areas combine several disciplines, requiring a diverse array of skills. Digital hearing aids, implantable defibrillators, artificial heart valves, and pacemakers are all bioengineering products that help people combat disease and disability. Bioengineers develop advanced therapeutic and surgical devices, such as a laser system for eye surgery and a pump that regulates automated delivery of insulin. In genetics, bioengineers try to detect, prevent, and treat genetic diseases. In sports medicine, bioengineers develop rehabilitation and external support devices. In industry, bioengineers work to understand the interaction between living systems and technology. Government bioengineers often work in product testing and safety, where they establish safety standards for medical devices and other consumer products. A biomedical engineer employed in a hospital might advise on the selection and use of medical equipment or supervise performance testing and maintenance.

In biocommunication, bioengineers develop new communication systems that enable paralyzed people to communicate directly with computers using brain waves. Through bioinformation engineering, they are exploring the remarkable properties of the human brain in pattern recognition and as a learning computer. Through biomimetics, bioengineers try to mimic living systems to create efficient designs. These areas have already developed far beyond the material in this chapter, but their basic themes are similar.

In this chapter, we introduce a few simple descriptions of human anatomy and study the effects of large forces on hard and soft human tissues. We also learn (1) why head injuries can be devastating, (2) why vehicle collisions can kill, (3) how to make a first approximation of the likelihood of damage during collisions to the human body using a fracture criterion, (4) how to predict the injury potential of a possible accident using a criterion that we call stress-speed-stopping distance-area (SSSA), and (5) how to apply the 30. g limit and the Gadd severity impact parameter on the human body.

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Bioengineering

Philip Kosky , ... George Wise , in Exploring Engineering (Third Edition), 2013

14.2 What do bioengineers do?

Bioengineers have a wide variety of career choices. Some work alongside medical practitioners, developing new medical techniques, medical devices, and instrumentation for manufacturing companies. Hospitals and clinics employ clinical engineers to maintain and improve the technological support systems used for patient care. Engineers with advanced bioengineering degrees can perform biological and medical research in educational and government research laboratories.

Many bioengineers help people by solving complex problems in medicine and health care. Some bioengineering jobs combine several disciplines, requiring a diverse array of skills. Digital hearing aids, implantable defibrillators, artificial heart valves, and pacemakers are all bioengineering products that help people combat disease and disability. Bioengineers develop advanced therapeutic and surgical devices, such as a laser system for eye surgery and a device that regulates automated delivery of insulin. In genetics, bioengineers try to detect, prevent, and treat genetic diseases. In sports medicine, bioengineers develop rehabilitation and external support devices. In industry, bioengineers work to understand the interaction between living systems and technology. Government bioengineers often work in product testing and safety, where they establish safety standards for medical devices and other consumer products. A biomedical engineer employed in a hospital might advise on the selection and use of medical equipment or supervise performance testing and maintenance.

In biocommunication, bioengineers develop new communication systems that enable paralyzed people to communicate directly with computers using brain waves. Through bioinformation engineering, they are exploring the remarkable properties of the human brain in pattern recognition and as a learning computer. Through biomimetics, bioengineers try to mimic living systems to create efficient designs. These areas range far beyond the material in this chapter, but their basic theme is similar.

By engineering analysis of the situations to which living matter might be exposed and by characterizing, in engineering terms, the remarkable properties of living matter, knowledge is gained that improves safety and health. That understanding can be used to make life safer and healthier. Among the tasks undertaken by bioengineers is the design of safety devices, ranging from football helmets to seat belts to air bags; the development of prosthetic devices for use in the human body, such as artificial hip joints; the application of powerful methods for imaging the human body, such as computed axial tomography (CT/CAT scanning) and magnetic resonance imaging (MRI); and the analysis and mitigation of possible harmful health effects on humans subject to extreme environments, such as the deep sea and outer space.

In this chapter, we introduce a few simple descriptions of human anatomy and the effects of large forces on hard and soft human tissues. We also learn (1) why collisions can kill, (2) how to make a first approximation of the likelihood of damage during collisions to the human body using a fracture criterion, (3) how to predict the injury potential of a possible accident using a criterion that we call "stress-speed-stopping distance-area" (SSSA), and (4) how to apply two other criteria for the effect of deceleration on the human body (the 30. g limit and the Gadd Severity Impact parameter).

We investigate just two areas of human anatomy: the first is to understand how serious blunt force trauma can affect the operation of the brain and other neurological tissue; the second is to understand how bone protects internal soft tissues.

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The role of biopolymers and biodegradable polymeric dressings in managing chronic wounds

Monica Puri Sikka , Vinay Kumar Midha , in Advanced Textiles for Wound Care (Second Edition), 2019

16.8 Stem cell therapy

The bioengineers, cell biologists and clinicians are facing challenges towards further development of ideal wound dressing template with ongoing interaction and collaborations. Stem cell therapy is a new milestone and strategy with the characteristics of self-renewal and multilineage differentiation. Identification and location of stem cells in skin have already been achieved and ongoing research proved the potential contribution of stem cells in the reconstitution of skin at the wound site. Epidermal keratinocytes have a poor regenerative capacity which can be overcome by utilising self-renewing keratinocyte stem cells. In the next decade, stem cell therapy will be a breakthrough in skin tissue engineering to generate skin substitutes that will completely mimic structures and function of the native skin [156–160].

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Adult and Fetal Stem Cells

Adam J. Katz , Alexander F. Mericli , in Handbook of Stem Cells (Second Edition), 2013

Local/Direct Application of ASCs

Collaboration between bioengineers and clinicians has yielded three-dimensional constructs tailored to address specific connective tissue contour demands. Several materials such as Matrigel®, alginate, and collagen sponges are ideal for adipose and endothelial tissue engineering but lack strong structural support. Poly(ethylene glycol)-based hydrogels have demonstrated the ability to promote adipogenic differentiation in vivo whereas apatite-coated polylactic-co-glycolic acid scaffolds have been used in concert with ASCs to treat calvarial (bony) defects in mice. It is theorized that the spacing and orientation that these engineered scaffolds provide are an important cue to the stem cells, inducing the adoption of the correct phenotype for the targeted tissue/defect.

Hao et al. (2010) demonstrated that ASCs transfected with BMP, and cultured on a nano-hydroxyapatite/recombinant human-like collagen/poly(lactic acid) scaffold, were able to produce complete bony healing at 12 weeks when implanted into a critical size defect in a rabbit radius. Levi at al. (2011) demonstrated that ASCs are only effective in rebuilding a critical-size calvarial defect in acute injury as opposed to what is perhaps a more clinically challenging chronic defect.

The localized delivery of ASCs to reconstruct and/or augment soft tissue is receiving great interest. One of the problems with direct application of ASCs seems to be poor/inefficient cell survival, which may explain highly variable preclinical and clinical results. It is theorized that this may be due in part to the damaging shearing forces that the cells are exposed to during injection. Moyer and colleagues (2010) demonstrated that alginate microencapsulation technology is efficacious for protecting ASCs during injection and maintain their viability once implanted in the soft tissue.

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Blood pressure monitors

Gail Baura , in Medical Device Technologies (Second Edition), 2021

Enabling technology: oscillometry

More recently, bioengineer and physician Maynard "Mike" Ramsey III developed the first automated BP monitor, based on oscillometry. Oscillometry is the analysis of pressure pulsations as an overinflated cuff over the brachial artery is deflated. It had been known that systolic pressure could be determined with oscillometry. Ramsey and his company, Applied Medical Research, demonstrated in 1977 that the mean pressure occurred when the peak-to-peak amplitude of the pulsation was maximal. MAP could be estimated accurately using an automated, microprocessor-controlled monitor (Ramsey, 1979) (Fig. 7.3). Ramsey sold his Dinamap technology to Johnson & Johnson Critikon in 1979. He then led a Critikon team that developed Critikon Dinamap BP monitors for measuring systolic, diastolic, and mean pressures (Szeto, 2002).

Figure 7.3. The first model of Dinamap marketed by Applied Research Corporation was the Model 825.

 Courtesy of Maynard Ramsey III, Tampa, Florida.

Auscultation and oscillometry are technologies for discrete, noninvasive blood pressure (NIBP) measurement. In the OR, it is desirable to continuously monitor BP noninvasively. To this end, continuous noninvasive blood pressure (cNIBP) monitors are being investigated. Some of the monitoring technologies that have been investigated are tonometry (Belani et al., 1999), variations of tonometry (Baura, 2002a, 2003), and the method of Penaz (Molhoek et al., 1984; Imholz, Wieling, Van Montfrans, & Wesseling, 1998). With tonometry, BP can be measured when sufficient force is applied to the radial artery, such that the transmural pressure equals zero and the external pressure equals the internal pressure (Pressman & Newgard, 1963). With the method of Penaz, BP can be measured when the cuff pressure at which finger pulse pressure amplitudes are maximized; this maximum is assumed to indicate when the arterial diameter is maximal (Penaz, 1969; Baura, 2002b).

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Introduction

Sylvain Ladame , in Bioengineering Innovative Solutions for Cancer, 2020

This textbook presents how bioengineers are tackling the many challenges our society faces to reduce the burden of cancer. Finding innovative solutions to cancer can take many forms that are presented and discussed in this book: developing new sensing and imaging technologies to detect cancer earlier and with increased precision; engineering new therapies and new nanotechnologies to improve their delivery; to developing new robotic tools to improve surgery's precision; and developing new models to better understand the various ways cancer cells form, propagate, and respond to treatment. Every branch of the very diverse field that is bioengineering has a role to play in addressing the many challenges caused by cancer, helping cancer patients live longer, healthier, and ultimately cancer-free.

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The Big Picture

John Semmlow , in Circuits, Signals and Systems for Bioengineers (Third Edition), 2018

1.1.1 Goals of This Book

The tools of MATLAB make it possible for bioengineers to better analyze and understand signals and systems, the bread and butter of our professional lives. This book helps you to make the most of this powerful computer language in its applications to signal processing and systems analysis. The objective of this book is to give the reader a fundamental understanding of the field traditionally known as "linear systems analysis," but with concepts and applications in bioengineering. The basic ideas of linear systems analysis are well established and well understood. They can be divided into areas of signal analysis, system analysis, and the application of systems to signals known as signal processing.

The goal of signal analysis is to extract information from a signal by identifying features that are of particular interest. This includes basic and refined descriptions of a signal's time representation and a breakdown of its frequency content. This book covers the how and why of examining the correlations that occur between different portions of a signal. We find that correlation is a useful tool in signal analysis: we use it to determine similarities between two signals. When we use correlation to compare a signal and the (almost mystical) sinusoidal waveform, we discover that a bunch of sinusoids can give an alternative, yet complete representation of almost any signal. Moreover, applying a little algebra to this alternative "sinusoidal" representation can give us the "frequency spectrum" (or just "spectrum") of the signal.

In systems analysis, the basic goal is to be able to describe, quantitatively, the response of a system to a wide variety of stimuli. We will first learn to define system behavior analytically using differential equations. However, as is typical of engineers, we will find an easy way solve these equations using algebra. When digital systems are involved, they are described using difference equation rather than differential equations, but again we solve them algebraically. Surpassing these traditional analysis methods in ease and power is continuous system simulation implemented here with MATLAB's powerful system simulation tool, Simulink. This tool allows us to describe the behavior of very complex systems, even those that include nonlinear elements.

Mixing signal and system analysis, we use some special systems to alter signals. Applying these systems to a signal can produce an altered signal that is more useful to us. Often this increased utility is achieved by removing distracting components from the signal (i.e., noise). For example, we might remove frequencies in the signal that do not contribute to the signal's information content. Using a system to remove unwanted frequencies is known as "filtering" and the special system that does this is called, logically, a filter.

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Tissue engineering of the kidney

Ji Hyun Kim , ... James J. Yoo , in Principles of Tissue Engineering (Fifth Edition), 2020

Decellularization/recellularization strategy

Recently, there have been numerous efforts to bioengineer complex 3D organs and tissues such as the heart, liver, lung, and kidney. Such organs have tissue-specific multicellular architecture and vasculature that is sophisticatedly organized to exert tissue-specific functions. Kidney, as mentioned earlier, is a highly complex organ composed of over 30 different cell types. Each cell type is intricately organized and functionally compartmentalized to form thousands of nephrons, the functional units of the kidney. Nephrons have different regions: the Bowman's capsule that encloses the glomerulus, the proximal tubule, the loop of Henle, the distal tubule, and the collecting duct. Each region has different anatomical features and physiological roles [12]. This complexity of the kidney makes it difficult to reproduce by traditional scaffold fabrication methodologies.

Recent progress in whole organ engineering, involving the decellularization/recellularization technologies, has provided a promising approach to overcome the limitations of traditional scaffold fabrication techniques and to build complex 3D kidney constructs (Table 45.3) [16–18]. Potentially, this technology may address the unmet medical problem of the shortage of transplantable donor kidneys via an alternative engineered whole kidney. In the decellularization/recellularization approach, acellular tissue is utilized as a scaffolding system. Acellular biologic scaffolds can be produced by removing cells from the tissues or organs through the "decellularization" process, leaving behind a tissue-specific ECM. The decellularized scaffolds can be seeded with cells, in a process called "recellularization" [17,132]. The decellularized tissues maintain the 3D ultrastructure and composition of the ECM, biochemical and biophysical factors, and vascular networks of the native tissues or organs. Over time, the decellularized tissue is degraded and remodeled with new ECM proteins produced by seeded cells. Therefore decellularizing tissues can produce an ideal scaffolding system to provide renal-specific microenvironments for engineering functional whole kidneys.

Table 45.3. Decellularization/recellularization strategy for whole kidney tissue engineering.

Species Decellularization Recellularization In vivo Outcome Refs.
Cells Seeding method Scaffold culture method
Rat 3% Triton X-10, DNase, 3% Triton X-100, 4% SDS. Gravity-based perfusion using renal artery and ureter (100   mmHg) Murine ESCs Manual injection through either the artery or ureter Automated perfusion system (120   mmHg/80   mmHg) – Proliferation and differentiation of ESCs in a complex architecture, production of basement membrane [122,123]
Pig 0.5% SDS for 36   h and DNase overnight, renal artery perfusion Human primary renal cells Static seeding Static culture for 3–4 days – Optimization of decellularization method [124]
Human Distilled water at 12   mL/min for 12   h, 0.5% SDS at 12   mL/min for 48   h, and final rinse with PBS at 6   mL/min for 5 days – – – – Optimization of decellularization methodAngiogenic capability [125]
Rhesus monkey 1% SDS, 7–10 days hESCs Static seeding into decellularized kidney sections Static culture for 8 days – Spatial organization cells into tissue-specific structures in vitro [126,127]
Rat 0.01   M PBS at 2   mL/min for 15   min, 0.5% SDS for 4   h, then PBS for 24   h, renal artery perfusion Mouse ESCs Manual seeding through the renal artery and ureter Perfusion culture Orthotopic implantation into rat Reperfusion and urine production with no blood leakage, obstruction of renal artery and vein by a massive thrombi [128]
Rat 1% Triton X-100 at 70   mL/h for 1   h 25   min, then PBS at 50   mL/h for 1   h Human pancreatic carcinoma cells Manual injection through renal arterial vascular network Perfusion bioreactor at 1   mL/min for 24   h Orthotopic implantation into rat Homogeneous cell distribution, obstruction of all vascular structures with thrombi [129]
Rat 1% SDS 12   h, 1% Triton X-100 30   min, renal artery perfusion (40   mmHg) Rat neonatal kidney cells and HUVECs HUVECs: Arterial flow (1   m/min) then static culture overnight, rat neonatal kidney cells: injected through the ureter Arterial perfusion culture in a bioreactor (1.5   mL/min) Orthotopic implantation into rat Graft perfusion by recipient's circulation, urine production through ureteral conduit [130]
Pig 0.5% SDS GFP-labeled endothelial cells (MS-1) Static seeding followed by ramping perfusion, conjugation of CD31 antibodies to the vascular matrix Perfusion rate at 2   mL/min and then gradually increased to 5, 10, and 20   mL/min at 10–12 intervals Orthotopic implantation into pig Improved endothelial cell retention on the vasculature, enhanced vascular patency of the implanted kidney in vivo [131]

ESC, Embryonic stem cell; GFP, green fluorescent protein; hESC, human embryonic stem cell; HUVEC, human umbilical vein endothelial cell; PBS, phosphate buffered saline; SDS, sodium dodecyl sulfate.

A variety of decellularization strategies have been developed to generate acellular renal scaffolds using rat [122,123,128–130], pig [124,131], rhesus monkey [126,127], and human [125] kidneys. An efficient decellularization technique is to remove the cellular components to avoid the induction of an immune response while preserving the 3D renal ECM architecture for glomerular and tubular structures and intact vascular networks. The general decellularization protocol for this approach is to perfuse detergents, enzymes, or other cell lysates such as sodium dodecyl sulfate, Triton X-100, and DNase through the inherent vasculature [17,132].

Initial success in kidney decellularization was achieved by Ross et al. in their work on rat whole kidneys [122,123]. Their decellularized rat kidneys preserved the intricate ECM architecture with intact vasculature. They then showed the possibility of using the decellularized kidney as a renal scaffold. They recellularized the acellular kidney scaffold with murine ESCs by manual injection through either the artery or ureter, showing the repopulation and differentiation of ESCs in the acellular kidney scaffolds. Thereafter, several groups have reported efficient decellularization technologies of whole kidneys in pig [131] and monkey [125,127] models to produce acellular renal scaffolds to recreate engineered whole kidney constructs on a clinical scale. Recently, Orlando et al. reported successful decellularization of human kidneys discarded from transplantation with an optimized decellularization protocol [125]. The resulting human whole kidney ECM scaffolds maintained their macro- and micro-3D architecture, biochemical properties, and vascular patency, showing the possibility of utilizing discarded human kidneys for acellular renal scaffolds in whole kidney transplantation.

There have been several attempts to recellularize decellularized whole kidneys to produce functional tissue or organs for transplantation. Early recellularization methods involved manual injection of cells through the renal artery and vein in static culture for several days; however, this approach results in low survival and growth, significant apoptosis, and an uneven distribution of cells [16]. Therefore an efficient recellularization strategy should be established for bioengineering implantable whole kidneys. Recently, a bioreactor system composed of a cell infusion and perfusion culture system such as syringe pump [133], peristaltic pump [130], or pulsatile pump [18,38] has been applied for this process. The bioreactor system allows for constant infusion of cells without apparent damage to the scaffold and supports nutrition, viability, proliferation, and differentiation of the cells within the scaffold [16].

In a recent report by Song et al., a bioengineered rat kidney construct was produced by decellularization/recellularization techniques using a bioreactor system and transplanted into rats [130]. A decellularized rat whole kidney was recellularized using human umbilical vein endothelial cells through the renal artery, and rat neonatal cells through the ureter with negative pressure on the whole kidney chamber, followed by arterial perfusion culture in a bioreactor as previously mentioned. Using this system, they achieved a high recellularization rate, with 70% glomeruli. In another study by Peloso et al., an acellular kidney was repopulated in a customized bioreactor system [129]. In this study, human pancreatic carcinoma cells were manually injected into decellularized rat kidneys through renal arterial vascular networks and cultured in a pulsatile system. In a short-term culture system, the cells were homogenously distributed inside the parenchyma.

Even with the success of these studies, the appropriate source of cells for recellularization is controversial. Current studies use different cell sources, including neonatal kidney cells [130], ESCs [122,123,126–128], primary human renal cells [124], and endothelial cells [130,131], to repopulate acellular kidney scaffolds. ESCs show superior outcomes in terms of differentiation into multiple types of renal cells in bioengineered kidney tissues; however, the use of ESCs in the clinic is still limited due to regulatory and ethical issues. Primary human renal cells or renal cells derived from hiPSCs, therefore, may be better candidates when considering clinical perspectives.

Although the decellularization/recellularization strategy has shown promising results in vitro and in vivo, several challenges need to be addressed for the successful transplantation of bioengineered whole kidneys. One of the critical challenges is the maintenance of long-term vascular patency of the bioengineered kidneys in vivo [128,129,131]. In a study by Peloso et al., mentioned earlier, it was reported that their implanted whole rat kidney was able to maintain blood perfusion after orthotopic transplantation for 7 days; however, the entire vascular network for the implant was obstructed by a massive thrombosis over time [129]. With this result, they highlighted that the reendothelialization of scaffold vasculature is mandatory for avoiding extensive thrombosis to establish successful transplantation and renal function. To address this issue, Ko et al. developed a novel endothelial seeding method that facilitated effective reendothelialization of a porcine kidney scaffold [131]. Conjugating CD31 antibodies to the vascular lumen increased endothelial cell attachment and retention on the vascular network, and resulted in reduced thrombosis and enhanced vascular patency of the bioengineered whole kidney in vivo.

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Artificial pancreas

Gail Baura , in Medical Device Technologies (Second Edition), 2021

Early devices

In contrast to this ideal, the artificial pancreas was first realized by bioengineer A. Michael Albisser's group as a closed-loop system consisting of a glucose analyzer, minicomputer, and two infusion pumps for insulin and dextrose (Fig. 20.11). The system was developed using pancreatized beagles (Albisser et al., 1974a) and clinically trialed in humans in 1974 (Albisser et al., 1974b). A few years later, in 1979, Miles Laboratories developed its Biostator Glucose Controlled Insulin Infusion System. This integrated system consisted of a blood pump, glucose analyzer, computer, infusion pump, and printer (Clemens, 1979). Both early systems were hampered by catheters in whole blood, oversimplified feedback control, large size, and constant need for clinical support.

Figure 20.11. Albisser's artificial pancreas.

 Adapted from Albisser et al. (1974a).

More recently, separate components for a future closed-loop system have been developed. The Cygnus GlucoWatch Biographer (Fig. 20.12) had a disposable sensor that noninvasively measured glucose 3 times per hour for 12 h. Using reverse iontophoresis, current from a 0.42-V load was applied, which brought ISF in contact with the sensor. ISF glucose reacted with the enzyme glucose oxidase, GOx, to form hydrogen peroxide, H2O2, after an intermediate product reacted with oxygen:

Figure 20.12. Photograph of the Glucowatch Biographer.

 Reproduced by permission from Tierney et al. (2001).

(20.28) FAD-GOx + glucose → FADH2-GOx + gluconolactone,

(20.29) FADH2-GOx + O 2 → H 2 O 2 .

For GOx to act as a catalyst in Eq. (20.29), the cofactor flavin adenine dinucleotide (FAD) was required. Hydrogen peroxide was detected by a platinum/carbon electrode through the reaction (McGarraugh, 2009):

(20.30) H 2 O 2 → 2 H + + O 2 + 2 e − .

Electrode current was passed to the Biographer circuitry, which translated the current to a blood glucose level for display. The sensor was initialized during a 3-h warm-up period, followed by calibration with a traditional glucose meter. After 12 h, a new sensor was required. In 420 glucose measurements submitted to the FDA, in which Biographer readings were compared to a standard glucose laboratory analyzer blood glucose readings, only 71% of glucose readings were within 20% of analyzer readings.

The Biographer was first approved by the FDA in 2001 (CDRH, 2001). In addition to inaccuracy, this sensor suffered from skipped readings, skin irritation, sweating precluding glucose measurements, and false alarms (Skyler, 2009). Its manufacture was discontinued in 2007 by Animas Corporation, which purchased Cygnus.

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Foreword

Professor Amit Gefen , in Innovations and Emerging Technologies in Wound Care, 2020

This cross-disciplinary book bridges the well-recognized gaps between clinicians and biomedical researchers or bioengineers, between basic scientists and practitioners, and between academia and industry—all of which are known to hinder progress in the field. The book is valuable for all professionals involved in the prevention, diagnosis, and treatment of chronic wounds and burns, concerning both clinical work and research and development, in academia, medical settings, and industry. The book contains contributed chapters of the leading experts on the subject matter and from all around the world. It is the best synthesis of wound research knowledge with regards to the tissue damage cascades and healing processes relevant to chronic wounds. The book further describes the state-of-the-art technology in wound prevention, diagnosis, prognosis, and treatment. In addition, it depicts the current and emerging research directions and future technology trends in the field of wound prevention and care, at the early stages of research and development in academia and industry. The book will hence be pivotal as a source of scientific knowledge for all professionals and graduate students focusing on the diagnosis, prevention, early detection, management, treatment, and care of chronic and nonhealing wounds.

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