Bioengineering Skin Substitutes for Wound Management-Perspectives and Challenges.

Non-healing wounds and skin losses constitute significant challenges for modern medicine and pharmacology. Conventional methods of wound treatment are effective in basic healthcare; however, they are insufficient in managing chronic wound and large skin defects, so novel, alternative methods of therapy are sought. Among the potentially innovative procedures, the use of skin substitutes may be a promising therapeutic method. Skin substitutes are a heterogeneous group of materials that are used to heal and close wounds and temporarily or permanently fulfill the functions of the skin. Classification can be based on the structure or type (biological and synthetic). Simple constructs (class I) have been widely researched over the years, and can be used in burns and ulcers. More complex substitutes (class II and III) are still studied, but these may be utilized in patients with deep skin defects. In addition, 3D bioprinting is a rapidly developing method used to create advanced skin constructs and their appendages. The aforementioned therapies represent an opportunity for treating patients with diabetic foot ulcers or deep skin burns. Despite these significant developments, further clinical trials are needed to allow the use skin substitutes in the personalized treatment of chronic wounds.

Sublinear drag regime at mesoscopic scales in viscoelastic materials.

Stressed soft materials commonly present viscoelastic signatures in the form of power-law or exponential decay. Although exponential responses are the most common, power-law time dependencies arise peculiarly in complex soft materials such as living cells. Understanding the microscale mechanisms that drive rheologic behaviors at the macroscale shall be transformative in fields such as material design and bioengineering. Using an elastic network model of macromolecules immersed in a viscous fluid, we numerically reproduce those characteristic viscoelastic relaxations and show how the microscopic interactions determine the rheologic response. The macromolecules, represented by particles in the network, interact with neighbors through a spring constant k and with fluid through a non-linear drag regime. The dissipative force is given by γvα, where v is the particle's velocity, and γ and α are mesoscopic parameters. Physically, the sublinear regime of the drag forces is related to micro-deformations of the macromolecules, while α ≥ 1 represents rigid cases. We obtain exponential or power-law relaxations or a transitional behavior between them by changing k, γ, and α. We find that exponential decays are indeed the most common behavior. However, power laws may arise when forces between the macromolecules and the fluid are sublinear. Our findings show that in materials not too soft not too elastic, the rheological responses are entirely controlled by α in the sublinear regime. More specifically, power-law responses arise for 0.3 ⪅ α ⪅ 0.45, while exponential responses for small and large values of α, namely, 0.0 ⪅ α ⪅ 0.2 and 0.55 ⪅ α ⪅ 1.0.

Cilia and Nodal Flow in Asymmetry: An Engineering Perspective.

Over the past several years, cilia in the primitive node have become recognized more and more for their contribution to development, and more specifically, for their role in axis determination. Although many of the mechanisms behind their influence remain undocumented, it is known that their presence and motion in the primitive node of developing embryos is the determinant of the left-right axis. Studies on cilial mechanics and nodal fluid dynamics have provided clues as to how this asymmetry mechanism works, and more importantly, have shown that direct manipulation of the flow field in the node can directly influence physiology. Although relatively uncommon, cilial disorders have been shown to have a variety of impacts on individuals from chronic respiratory infections to infertility, as well as situs inversus which is linked to congenital heart disease. After first providing background information pertinent to understanding nodal flow and information on why this discussion is important, this paper aims to give a review of the history of nodal cilia investigations, an overview of cilia mechanics and nodal flow dynamics, as well as a review of research studies current and past that sought to understand the mechanisms behind nodal cilia's involvement in symmetry-breaking pathways through a biomedical engineering perspective. This discussion has the additional intention to compile interdisciplinary knowledge on asymmetry and development such that it may encourage more collaborative efforts between the sciences on this topic, as well as provide insight on potential paths forward in the field.

teemi: An open-source literate programming approach for iterative design-build-test-learn cycles in bioengineering.

Synthetic biology dictates the data-driven engineering of biocatalysis, cellular functions, and organism behavior. Integral to synthetic biology is the aspiration to efficiently find, access, interoperate, and reuse high-quality data on genotype-phenotype relationships of native and engineered biosystems under FAIR principles, and from this facilitate forward-engineering strategies. However, biology is complex at the regulatory level, and noisy at the operational level, thus necessitating systematic and diligent data handling at all levels of the design, build, and test phases in order to maximize learning in the iterative design-build-test-learn engineering cycle. To enable user-friendly simulation, organization, and guidance for the engineering of biosystems, we have developed an open-source python-based computer-aided design and analysis platform operating under a literate programming user-interface hosted on Github. The platform is called teemi and is fully compliant with FAIR principles. In this study we apply teemi for i) designing and simulating bioengineering, ii) integrating and analyzing multivariate datasets, and iii) machine-learning for predictive engineering of metabolic pathway designs for production of a key precursor to medicinal alkaloids in yeast. The teemi platform is publicly available at PyPi and GitHub.

Progress in the development of piezoelectric biomaterials for tissue remodeling.

Piezoelectric biomaterials have demonstrated significant potential in the past few decades to heal damaged tissue and restore cellular functionalities. Herein, we discuss the role of bioelectricity in tissue remodeling and explore ways to mimic such tissue-like properties in synthetic biomaterials. In the past decade, biomedical engineers have adopted emerging functional biomaterials-based tissue engineering approaches using innovative bioelectronic stimulation protocols based on dynamic stimuli to direct cellular activation, proliferation, and differentiation on engineered biomaterial constructs. The primary focus of this review is to discuss the concepts of piezoelectric energy harvesting, piezoelectric materials, and their application in soft (skin and neural) and hard (dental and bone) tissue regeneration. While discussing the prospective applications as an engineered tissue, an important distinction has been made between piezoceramics, piezopolymers, and their composites. The superiority of piezopolymers over piezoceramics to circumvent issues such as stiffness mismatch, biocompatibility, and biodegradability are highlighted. We aim to provide a comprehensive review of the field and identify opportunities for the future to develop clinically relevant and state-of-the-art biomaterials for personalized and remote health care.

[Integration of "tri-bio, tri-chain and tri-creation" innovation and entrepreneurship education into talent training program].

Under the background of the "era of mass innovation", there are challenges in the training of biotechnology professionals, including a "backward concept of innovation and entrepreneurship education", a "singular education method of innovation and entrepreneurship", and a "limited practice platform of innovation and entrepreneurship". These challenges require the implementation of a new training model. In comparison to the talent training objectives of new engineering construction, the College of Biotechnology and Bioengineering at Zhejiang University of Technology has been exploring and practicing the training mode "tri-bio, tri-chain and tri-creation " for 42 years. The research has established a new platform and paradigm for training exceptional engineering innovation and entrepreneurship talents. It also offers valuable references and insights for the reform of training methods for biotechnology professionals by optimizing the education concept of "biology, life and live ", enriching the education method of "knowledge chain, scientific research chain and industrial chain", and building the three-creation technology practice platform based on "creativity, innovation and entrepreneurship".

Bioengineering of vascularized porcine flaps using perfusion-recellularization.

Large volume soft tissue defects greatly impact patient quality of life and function while suitable repair options remain a challenge in reconstructive surgery. Engineered flaps could represent a clinically translatable option that may circumvent issues related to donor site morbidity and tissue availability. Herein, we describe the regeneration of vascularized porcine flaps, specifically of the omentum and tensor fascia lata (TFL) flaps, using a tissue engineering perfusion-decellularization and recellularization approach. Flaps were decellularized using a low concentration sodium dodecyl sulfate (SDS) detergent perfusion to generate an acellular scaffold with retained extracellular matrix (ECM) components while removing underlying cellular and nuclear contents. A perfusion-recellularization strategy allowed for seeding of acellular flaps with a co-culture of human umbilical vein endothelial cell (HUVEC) and mesenchymal stromal cells (MSC) onto the decellularized omentum and TFL flaps. Our recellularization technique demonstrated evidence of intravascular cell attachment, as well as markers of endothelial and mesenchymal phenotype. Altogether, our findings support the potential of using bioengineered porcine flaps as a novel, clinically-translatable strategy for future application in reconstructive surgery.

Hybrid Soft-Rigid Active Prosthetics Laboratory Exercise for Hands-On Biomechanical and Biomedical Engineering Education.

This paper introduces a hands-on laboratory exercise focused on assembling and testing a hybrid soft-rigid active finger prosthetic for biomechanical and biomedical engineering (BME) education. This hands-on laboratory activity focuses on the design of a myoelectric finger prosthesis, integrating mechanical, electrical, sensor (i.e., inertial measurement units (IMUs), electromyography (EMG)), pneumatics, and embedded software concepts. We expose students to a hybrid soft-rigid robotic system, offering a flexible, modifiable lab activity that can be tailored to instructors' needs and curriculum requirements. All necessary files are made available in an open-access format for implementation. Off-the-shelf components are all purchasable through global vendors (e.g., DigiKey Electronics, McMaster-Carr, Amazon), costing approximately USD 100 per kit, largely with reusable elements. We piloted this lab with 40 undergraduate engineering students in a neural and rehabilitation engineering upper year elective course, receiving excellent positive feedback. Rooted in real-world applications, the lab is an engaging pedagogical platform, as students are eager to learn about systems with tangible impacts. Extensions to the lab, such as follow-up clinical (e.g., prosthetist) and/or technical (e.g., user-device interface design) discussion, are a natural means to deepen and promote interdisciplinary hands-on learning experiences. In conclusion, the lab session provides an engaging journey through the lifecycle of the prosthetic finger research and design process, spanning conceptualization and creation to the final assembly and testing phases.

Influence of Ultrasound on the Characteristics of CaP Coatings Generated Via the Micro-arc Oxidation Process in Relation to Biomedical Engineering.

Over the past decade, bone tissue engineering has been at the core of attention because of an increasing number of implant surgeries. The purpose of this study was to obtain coatings on titanium (Ti) implants with improved properties in terms of biomedical applications and to investigate the effect of ultrasound (US) on these properties during the micro-arc oxidation (MAO) process. The influence of various process parameters, such as time and current density, as well as US mode, on the properties of such coatings was evaluated. Novel porous calcium-phosphate-based coatings were obtained on commercially pure Ti. Their microstructure, chemical composition, topography, wettability, nanomechanical properties, thickness, adhesion to the substrate, and corrosion resistance were analyzed. In addition, cytocompatibility evaluation was checked with the human osteoblasts. The properties of the coatings varied significantly, depending on applied process parameters. The US application during the MAO process contributes to the increase of coating thickness, porosity, roughness, and skewness, as well as augmented calcium incorporation. The most advantageous coating was obtained at a current of 136 mA, time 450 s, and unipolar rectangular US, as it exhibits high porosity, adequate wettability, and beneficial skewness, which enabled increased adhesion and proliferation of osteoblasts during in vitro studies. Finally, the conducted research demonstrated the influence of various UMAO process parameters, which allowed for the selection of appropriate Ti implant modification for specific biomedical utilization.

Open microfluidics: droplet microarrays as next generation multiwell plates for high throughput screening.

Multiwell plates are prominent in the biological and chemical sciences; however, they face limitations in terms of throughput and deployment in emerging bioengineering fields. Droplet microarrays, as an open microfluidic technology, organise tiny droplets typically in the order of thousands, on an accessible plate. In this perspective, we summarise current approaches for generating droplets, fluid handling on them, and analysis within droplet microarrays. By enabling unique plate engineering opportunities, demonstrating the necessary experimental procedures required for manipulating and interacting with biological cells, and integrating with label-free analytical techniques, droplet microarrays can be deployed across a more extensive experimental domain than what is currently covered by multiwell plates. Droplet microarrays thus offer a solution to the bottlenecks associated with multiwell plates, particularly in the areas of biological cultivation and high-throughput compound screening.

Recent advances in peptide-based bioactive hydrogels for nerve repair and regeneration: from material design to fabrication, functional tailoring and applications.

The injury of both central and peripheral nervous systems can result in neurological disorders and severe nervous diseases, which has been one of the challenges in the medical field. The use of peptide-based hydrogels for nerve repair and regeneration (NRR) provides a promising way for treating these problems, but the effects of the functions of peptide hydrogels on the NRR efficiency have been not understood clearly. In this review, we present recent advances in the material design, matrix fabrication, functional tailoring, and NRR applications of three types of peptide-based hydrogels, including pure peptide hydrogels, other component-functionalized peptide hydrogels, and peptide-modified polymer hydrogels. The case studies on the utilization of various peptide-based hydrogels for NRR are introduced and analyzed, in which the effects and mechanisms of the functions of hydrogels on NRR are illustrated specifically. In addition, the fabrication of medical NRR scaffolds and devices for pre-clinical application is demonstrated. Finally, we provide potential directions on the development of this promising topic. This comprehensive review could be valuable for readers to know the design and synthesis strategies of bioactive peptide hydrogels, as well as their functional tailoring, in order to promote their practical applications in tissue engineering, biomedical engineering, and materials science.

Catalyzing Clinically Driven Undergraduate Design Projects at the Nexus of Engineering, Medicine, and Business.

Design projects, particularly those related to assistive technology, offer unparalleled educational opportunities for undergraduate students to synthesize engineering knowledge with a clinically driven need to produce a product that can improve quality of life. Such projects are most effective when engineering, clinical, and business perspectives are considered throughout. However, the logistics of successfully implementing such interdisciplinary projects can be challenging. This paper presents an auto-ethnography of 12 undergraduate design team projects in assistive technology performed by 87 students from five majors (including engineering, business, and clinical students) over the course of 5 years. The overarching goal of our work was to establish an undergraduate integrated design experience at a university in the absence of a dedicated biomedical engineering major. The focus of this experience was to foster the creation of student-led prototypes to address real-world problems for people with disabilities while keeping commercialization potential at the forefront throughout. Student participation demonstrated a clear enthusiasm for completing biomedical engineering-themed projects. To encourage the implementation of similar approaches at universities where a biomedical engineering major does not exist, we identify common obstacles that can arise and present strategies for mitigating these challenges, as well as effective approaches for catalyzing cross-disciplinary collaborations. High impact practices include close involvement of end-users in the design process; cross-disciplinary team composition (e.g., engineering, business, and health sciences students); and choosing cross-disciplinary leads for project management. Teams experienced a high degree of success with all 12 teams producing functional prototypes. We conclude that at universities that do not offer a biomedical engineering major, health-focused integrated design experiences offer students important interdisciplinary perspectives, including a holistic approach to project implementation. Furthermore, for many students, these projects ultimately served as a gateway to subsequent careers and graduate study in biomedical engineering.

Building a Partnership Between a University and Local High School to Foster and Grow Interest in Biomedical Sciences and Engineering.

To help foster interest in science, technology, engineering, and math (STEM), it is important to develop opportunities that excite and teach young minds about STEM-related fields. Over the past several years, our university-based research group has sought to help grow excitement around the biomechanics and biomedical engineering fields. The purposes of this technical brief are to (1) discuss the development of a partnership built between a St. Louis area high school and biomechanics research lab and (2) provide practical guidance for other researchers looking to implement a long-term outreach program. The partnership uses three different outreach opportunities. The first opportunity consisted of 12th-grade students visiting university research labs for an up-close perspective of ongoing biomedical research. The second opportunity was a biomedical research showcase where research-active graduate students traveled to the high school to perform demonstrations. The third opportunity consisted of a collaborative capstone project where a high school student was able to carry out research directly in a university lab. To date, we have expanded our reach from 19 students to interacting with over 100 students, which has yielded increased interest in STEM related research. Our postprogram survey showed that outreach programs such as the one described herein can increase interest in STEM within all ages of high school students. Building partnerships between high schools and university researchers increases the interest in STEM amongst high school students, and gives graduate students an outlet to present work to an eager-to-learn audience.

A review on complete silk gene sequencing and de novo assembly of artificial silk.

Silk, especially spider and insect silk, is a highly versatile biomaterial with potential applications in biomedicine, materials science, and biomimetic engineering. The primary structure of silk proteins is the basis for the mechanical properties of silk fibers. Biotechnologies such as single-molecule sequencing have facilitated an increasing number of reports on new silk genes and assembled silk proteins. Therefore, this review aims to provide a comprehensive overview of the recent advances in representative spider and insect silk proteins, focusing on identification methods, sequence characteristics, and de novo design and assembly. The review discusses three identification methods for silk genes: polymerase chain reaction (PCR)-based sequencing, PCR-free cloning and sequencing, and whole-genome sequencing. Moreover, it reveals the main spider and insect silk proteins and their sequences. Subsequent de novo assembly of artificial silk is covered and future research directions in the field of silk proteins, including new silk genes, customizable artificial silk, and the expansion of silk production and applications are discussed. This review provides a basis for the genetic aspects of silk production and the potential applications of artificial silk in material science and biomedical engineering.

Label-Free DNA Hybridization Detection Using a Highly Sensitive Fiber Microcavity Biosensor.

A novel label-free optical fiber biosensor, based on a microcavity fiber Mach-Zehnder interferometer, was developed and practically demonstrated for DNA detection. The biosensor was fabricated using offset splicing standard communication single-mode fibers (SMFs). The light path of the sensor was influenced by the liquid sample in the offset open cavity. In the experiment, a high sensitivity of -17,905 nm/RIU was achieved in the refractive index (RI) measurement. On this basis, the probe DNA (pDNA) was immobilized onto the sensor's surface using APTES, enabling real-time monitoring of captured complementary DNA (cDNA) samples. The experimental results demonstrate that the biosensor exhibited a high sensitivity of 0.32 nm/fM and a limit of detection of 48.9 aM. Meanwhile, the sensor has highly repeatable and specific performance. This work reports an easy-to-manufacture, ultrasensitive, and label-free DNA biosensor, which has significant potential applications in medical diagnostics, bioengineering, gene identification, environmental science, and other biological fields.

Letter to the Editor: "How Can Biomedical Engineers Help Empower Individuals With Intellectual Disabilities? The Potential Benefits and Challenges of AI Technologies to Support Inclusivity and Transform Lives".

The rapid advancement of Artificial Intelligence (AI) is transforming healthcare and daily life, offering great opportunities but also posing ethical and societal challenges. To ensure AI benefits all individuals, including those with intellectual disabilities, the focus should be on adaptive technology that can adapt to the unique needs of the user. Biomedical engineers have an interdisciplinary background that helps them to lead multidisciplinary teams in the development of human-centered AI solutions. These solutions can personalize learning, enhance communication, and improve accessibility for individuals with intellectual disabilities. Furthermore, AI can aid in healthcare research, diagnostics, and therapy. The ethical use of AI in healthcare and the collaboration of AI with human expertise must be emphasized. Public funding for inclusive research is encouraged, promoting equity and economic growth while empowering those with intellectual disabilities in society.

Modeling Shiga toxin-induced human renal-specific microvascular injury.

Shiga toxin (Stx) causes significant renal microvascular injury and kidney failure in the pediatric population, and an effective targeted therapy has yet to be demonstrated. Here we established a human kidney microvascular endothelial cell line for the study of Stx mediated injuries with respect to their morphologic, phenotypic, and transcriptional changes, and modeled Stx induced thrombotic microangiopathy (TMA) in flow-mediated 3D microvessels. Distinct from other endothelial cell lines, both isolated primary and immortalized human kidney microvascular endothelial cells demonstrate robust cell-surface expression of the Stx receptor Gb3, and concomitant dose-dependent toxicity to Stx, with significant contributions from caspase-dependent cell death. Use of a glucosylceramide synthase inhibitor (GCSi) to target disruption of the synthetic pathway of Gb3 resulted in remarkable protection of kidney microvascular cells from Stx injury, shown in both cellular morphologies, caspase activation and transcriptional analysis from RNA sequencing. Importantly, these findings are recapitulated in 3D engineered kidney microvessels under flow. Moreover, whole blood perfusion through Stx-treated microvessels led to marked platelet binding on the vessel wall, which was significantly reduced with the treatment of GCSi. These results validate the feasibility and utility of a bioengineered ex vivo human microvascular model under flow to recapitulate relevant blood-endothelial interactions in STEC-HUS. The profound protection afforded by GCSi demonstrates a preclinical opportunity for investigation in human tissue approximating physiologic conditions. Moreover, this work provides a broad foundation for novel investigation into TMA injury pathogenesis and treatment. Insight Box: Shiga toxin (Stx) causes endothelial injury that results in significant morbidity and mortality in the pediatric population, with no effective targeted therapy. This paper utilizes human kidney microvascular cells to examine Stx mediated cell death in both 2D culture and flow-mediated 3D microvessels, with injured microvessels also developing marked platelet binding and thrombi formation when perfused with blood, consistent with the clinical picture of HUS. This injury is abrogated with a small molecule inhibitor targeting the synthetic pathway of the Shiga toxin receptor. Our findings shed light onto Stx-induced vascular injuries and pave a way for broad investigation into thrombotic microangiopathies.

Performance of textured dual mobility total hip prosthesis with a concave dimple during Muslim prayer movements.

The single mobility bearing as a previous bearing design of total hip prosthesis has severe mobility constraints that can result in dislocation during Muslim (people who follow the Islam as religion) prayer movements, specifically shalat that requires intense movement. There are five intense movements (i.e., bowing, prostration, sitting, transition from standing to prostration, and final sitting) during Muslim prayer that may generate an impingement problem for patients with total hip prosthesis. In this work, textured dual mobility total hip prosthesis with two textured cases (i.e., textured femoral head and textured inner liner) are presented and their performances are numerically evaluated against untextured surface model during Muslim prayer movement. The concave dimple design is chosen for surface texturing, while for simulating femoral head materials, SS 316L and CoCrMo is choosen. To represent the real condition, three-dimensional computational fluid dynamics (CFD) coupled with two-way fluid-structure interaction (FSI) methods are employed to analyze elastohydrodynamic lubrication problem with non-Newtonian synovial fluid model. The main aim of the present study is to investigate the tribological performance on dual mobility total hip prosthesis with applied textured surface with concave dimple in femoral head and inner liner surface under Muslim prayer movements. It is found that applying surface texturing has a beneficial effect on the lubrication performance for some intense movements. The textured femoral head model performs better than textured inner liner model and untextured model (both femoral head and inner liner). The numerical results also indicate superior performance of CoCrMo femoral head compared to SS 316L femoral head. These findings can be used as a reference for biomedical engineers and orthopedic surgeons in designing and choosing suitable total hip prosthesis for Muslims makes they can carry out Muslim prayer movements like humans in general who have normal hip joints.

Current Advances in Photodynamic Therapy (PDT) and the Future Potential of PDT-Combinatorial Cancer Therapies.

Photodynamic therapy (PDT) is a two-stage treatment that implies the use of light energy, oxygen, and light-activated compounds (photosensitizers) to elicit cancerous and precancerous cell death after light activation (phototoxicity). The biophysical, bioengineering aspects and its combinations with other strategies are highlighted in this review, both conceptually and as they are currently applied clinically. We further explore the recent advancements of PDT with the use of nanotechnology, including quantum dots as innovative photosensitizers or energy donors as well as the combination of PDT with radiotherapy and immunotherapy as future promising cancer treatments. Finally, we emphasize the potential significance of organoids as physiologically relevant models for PDT.