Application of the Stanford Biodesign Framework in Healthcare Innovation Training and Commercialization of Market Appropriate Products: A Scoping Review.

The Stanford Biodesign needs-centric framework can guide healthcare innovators to successfully adopt the 'Identify, Invent and Implement' framework and develop new healthcare innovations products to address patients' needs. This scoping review explored the application of the Stanford Biodesign framework for healthcare innovation training and the development of novel healthcare innovative products. Seven electronic databases were searched from their respective inception dates till April 2023: PubMed, Embase, CINAHL, PsycINFO, Web of Science, Scopus, ProQuest Dissertations, and Theses Global. This review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews and was guided by the Arksey and O'Malley's scoping review framework. Findings were analyzed using Braun and Clarke's thematic analysis framework. Three themes and eight subthemes were identified from the 26 included articles. The main themes are: (1) Making a mark on healthcare innovation, (2) Secrets behind success, and (3) The next steps. The Stanford Biodesign framework guided healthcare innovation teams to develop new medical products and achieve better patient health outcomes through the induction of training programs and the development of novel products. Training programs adopting the Stanford Biodesign approach were found to be successful in improving trainees' entrepreneurship, innovation, and leadership skills and should continue to be promoted. To aid innovators in commercializing their newly developed medical products, additional support such as securing funds for early start-up companies, involving clinicians and users in product testing and validation, and establishing new guidelines and protocols for the new healthcare products would be needed.

Otologic use of porcine small intestinal submucosal graft (biodesign): A MAUDE database review.

OBJECTIVE: To review and summarize reported adverse events related to the use of porcine small intestine submucosal grafts (Biodesign™) in otologic procedures. STUDY DESIGN: Retrospective cross-sectional analysis. SETTING: Food and Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) database. MATERIAL AND METHODS: The MAUDE database was queried for all medical device reports (MDR) related to otologic use of Biodesign™ (Cook Medical, Bloomington, IN) from January 2016 to November 2022. Adverse events (AEs) were identified by reviewing all reports with the basic search term "Biodesign" and "Biodesign, Otologic". Reports were individually reviewed and categorized with special attention to AEs. RESULTS: A total of 500 reports were reviewed. Since FDA approval of Biodesign™ in 2016, there have been 5 adverse events reported for use of Biodesign™ during otologic surgery (tympanoplasty, n = 3; stapes surgery, n = 2). All reported events described patient injury, and all cases required at least one revision surgery. Four cases described significant foreign body inflammatory reactions. Complications included hearing loss (n = 3), severe otalgia (n = 2), persistent perforation (n = 2), vertigo (n = 2), and facial paralysis (n = 1). CONCLUSION: The use of porcine small intestinal submucosal graft has been thought to be a safe and effective option for otologic surgery, with the advantage of availability without graft harvest in minimally invasive endoscopic surgery. However, foreign body or granulomatous reactions have been documented and should be considered prior to its use in otologic surgery.

Biodesign program introduction in Japan: promotion of entrepreneurship and viewpoints of education on medical technology innovation.

The Stanford Biodesign program was first introduced in Japan in 2015 at three national universities to develop medical technology innovation and its talent. This study aimed to (1) show the outcomes of leadership talent development, (2) indicate the educational results of the program, and (3) objectively analyze the ways in which the program executed in Japan, effectively promoted entrepreneurship orientation and the origination of new businesses. The latter is especially relevant as Japan has low entrepreneurial awareness and new business entry rates compared to the United States and Europe. Herein, fellows were subjected to questionnaires, interviews, and a survey based on academic papers, extant literature, and treatises issued by the Nihon Biodesign Gakkai (Academic Society of Japan Biodesign). Overall program performance showed notable results, despite indicating a need to improve business-related programs and team learning which is greatly influenced by Japanese culture. An externship program, planned and developed in Japan, was most inspiring and served to expose participants to role models. Comparing Japan Biodesign education elements to factors of general entrepreneurship promotion in Japan, sampled and organized from relevant White Papers, proved its educational effectiveness in entrepreneurship promotion from an objective viewpoint. Within the 4-year timeframe, the results indicated that leadership talent was indeed developed. Medical device innovation should progress through the stages of establishing new ventures, followed by contriving medical devices with novel, impactful value. This study revealed that Japan Biodesign education provides a platform for achieving these goals, despite the challenging Japanese new business environment.

Identification of potential Mpro inhibitors for the treatment of COVID-19 by using systematic virtual screening approach.

The Corona virus Disease (COVID-19) is caused because of novel coronavirus (SARS-CoV-2) pathogen detected in China for the first time, and from there it spread across the globe creating a worldwide pandemic of severe respiratory complications. The virus requires structural and non-structural proteins for its multiplication that are produced from polyproteins obtained by translation of its genomic RNA. These polyproteins are converted into structural and non-structural proteins mainly by the main protease (Mpro). A systematic screening of a drug library (having drugs and diagnostic agents which are approved by FDA or other world authorities) and the Asinex BioDesign library was carried out using pharmacophore and sequential conformational precision level filters using the Schrodinger Suite. From the screening of approved drug library, three antiviral agents ritonavir, nelfinavir and saquinavir were predicted to be the most potent Mpro inhibitors. Apart from these pralmorelin, iodixanol and iotrolan were also identified from the systematic screening. As iodixanol and iotrolan carry some limitations, structural modifications in them could lead to stable and safer antiviral agents. Screenings of Asinex BioDesign library resulted in 20 molecules exhibiting promising interactions with the target protein Mpro. They can broadly be categorized into four classes based on the nature of the scaffold, viz. disubstituted pyrazoles, cyclic amides, pyrrolidine-based compounds and miscellaneous derivatives. These could be used as potential molecules or hits for further drug development to obtain clinically useful therapeutic agents for the treatment of COVID-19.

Post-stapedotomy reparative granuloma following use of acellular porcine small intestinal submucosa.

PURPOSE: There have been multiple proposed etiologies of reparative granuloma following stapes surgery. In this report, we present the first case of post-stapedectomy reparative granuloma following the use of Biodesign (Cook Medical, Bloomington, IN) otologic graft material, an acellular matrix derived from porcine small intestinal submucosa, and review the literature of post-stapes surgery reparative granuloma. PATIENT: 50-year-old woman who developed a reparative granuloma following stapedotomy with acellular porcine intestinal submucosa presenting with profound hearing loss and vertigo. INTERVENTION: Middle ear exploration with excision of granuloma and revision stapedotomy. MAIN OUTCOME MEASURES: Audiologic outcomes as measured by pure-tone air and bone conduction thresholds and word recognition scores. Improvement in vertigo. MAIN FINDINGS: Surgical excision of the reparative granuloma with revision stapedotomy resolved vertigo. Hearing has improved progressively postoperatively. CONCLUSIONS: We report the first case of post-stapedotomy reparative granuloma following the use of acellular porcine intestinal submucosa. Although exact etiology cannot be determined from a single case report, this illustrates the need for careful use of novel foreign graft material. This case additionally confirms that removal of granuloma and inciting materials can salvage serviceable hearing.

Turning Practicing Surgeons Into Health Technology Innovators: Outcomes From the Stanford Biodesign Faculty Fellowship.

Background. The Stanford Biodesign Faculty Fellows program was established in 2014 to train Stanford Medical and Engineering faculty in a repeatable innovation process for health technology translation while also being compatible with the busy clinical schedules of surgical faculty members. Methods. Since 2014, 62 faculty members have completed the fellowship with 42% (n = 26) coming from 14 surgical subspecialties. This eight-month, needs-based innovation program covers topics from identifying unmet health-related needs, to inventing new technology, developing plans for intellectual property (IP), regulatory, reimbursement, and business models to advance the technologies toward patient care. Results/Conclusion. Intake and exit survey results from three years of program participants (n = 36) indicate that the fellowship is a valuable hands-on educational program capable of improving awareness and experience with skill sets required for health technology innovation and entrepreneurship.

Drawing on the Past to Shape the Future of Synthetic Yeast Research.

Some years inspire more hindsight reflection and future-gazing than others. This is even more so in 2020 with its evocation of perfect vision and the landmark ring to it. However, no futurist can reliably predict what the world will look like the next time that a year's first two digits will match the second two digits-a numerical pattern that only occurs once in a century. As we leap into a new decade, amid uncertainties triggered by unforeseen global events-such as the outbreak of a worldwide pandemic, the accompanying economic hardship, and intensifying geopolitical tensions-it is important to note the blistering pace of 21st century technological developments indicate that while hindsight might be 20/20, foresight is 50/50. The history of science shows us that imaginative ideas, research excellence, and collaborative innovation can, for example, significantly contribute to the economic, cultural, social, and environmental recovery of a post-COVID-19 world. This article reflects on a history of yeast research to indicate the potential that arises from advances in science, and how this can contribute to the ongoing recovery and development of human society. Future breakthroughs in synthetic genomics are likely to unlock new avenues of impactful discoveries and solutions to some of the world's greatest challenges.

Protein hyperproduction in fungi by design.

The secretion of enzymes used by fungi to digest their environment has been exploited by humans for centuries for food and beverage production. More than a century after the first biotechnology patent, we know that the enzyme cocktails secreted by these amazing organisms have tremendous use across a number of industrial processes. Secreting the maximum titer of enzymes is critical to the economic feasibility of these processes. Traditional mutagenesis and screening approaches have generated the vast majority of strains used by industry for the production of enzymes. Until the emergence of economical next generation DNA sequencing platforms, the majority of the genes mutated in these screens remained uncharacterized at the sequence level. In addition, mutagenesis comes with a cost to an organism's fitness, making tractable rational strain design approaches an attractive alternative. As an alternative to traditional mutagenesis and screening, controlled manipulation of multiple genes involved in processes that impact the ability of a fungus to sense its environment, regulate transcription of enzyme-encoding genes, and efficiently secrete these proteins will allow for rational design of improved fungal protein production strains.

Scaling up genetic circuit design for cellular computing: advances and prospects.

Synthetic biology aims to engineer and redesign biological systems for useful real-world applications in biomanufacturing, biosensing and biotherapy following a typical design-build-test cycle. Inspired from computer science and electronics, synthetic gene circuits have been designed to exhibit control over the flow of information in biological systems. Two types are Boolean logic inspired TRUE or FALSE digital logic and graded analog computation. Key principles for gene circuit engineering include modularity, orthogonality, predictability and reliability. Initial circuits in the field were small and hampered by a lack of modular and orthogonal components, however in recent years the library of available parts has increased vastly. New tools for high throughput DNA assembly and characterization have been developed enabling rapid prototyping, systematic in situ characterization, as well as automated design and assembly of circuits. Recently implemented computing paradigms in circuit memory and distributed computing using cell consortia will also be discussed. Finally, we will examine existing challenges in building predictable large-scale circuits including modularity, context dependency and metabolic burden as well as tools and methods used to resolve them. These new trends and techniques have the potential to accelerate design of larger gene circuits and result in an increase in our basic understanding of circuit and host behaviour.

An Extended Hackathon Model for Collaborative Education in Medical Innovation.

To support the next generation of healthcare innovators - whether they be engineers, designers, clinicians, or business experts by training - education in the emerging field of medical innovation should be made easily and widely accessible to undergraduate students, graduate students, and young professionals, early in their careers. Currently, medical innovation curricula are taught through semester-long courses or year-long fellowships at a handful of universities, reaching only a limited demographic of participants. This study describes the structure and preliminary outcomes of a 1-2 week "extended hackathon" course that seeks to make medical innovation education and training more accessible and easily adoptable for academic medical centers. Eight extended hackathons were hosted in five international locations reaching 245 participants: Beijing (June 2015 and August 2016), Hong Kong (June 2016, 2017, and 2018), Curitiba (July 2016), Stanford (October 2017), and São Paulo (May 2018). Pre- and post-hackathon surveys asking respondents to self-assess their knowledge in ten categories of medical innovation were administered to quantify the perceived degree of learning. Participants hailed from a diverse range of educational backgrounds, domains of expertise, and academic institutions. On average, respondents (n = 161) saw a greater than twofold increase (114.1%, P < 0.001) from their pre- to post-hackathon scores. In this study, the extended hackathon is presented as a novel educational model to teach undergraduate and graduate students a foundational skillset for medical innovation. Participants reported gaining significant knowledge across all ten categories assessed. To more robustly assess the educational value of extended hackathons, a standardized assessment for medical innovation knowledge needs to be developed, and a larger sample size of participants surveyed.

An engineering biology approach to automated workflow and biodesign.

The paper addresses the application of engineering biology strategies and techniques to the automation of laboratory workflow-primarily in the context of biofoundries and biodesign applications based on the Design, Build, Test and Learn paradigm. The trend toward greater automation comes with its own set of challenges. On the one hand, automation is associated with higher throughput and higher replicability. On the other hand, the implementation of an automated workflow requires an instruction set that is far more extensive than that required for a manual workflow. Automated tasks must also be conducted in the order specified in the workflow, with the right logic, utilizing suitable biofoundry resources, and at scale-while simultaneously collecting measurements and associated data. The paper describes an approach to an automated workflow that is being trialed at the London Biofoundry at SynbiCITE. The solution represents workflows with directed graphs, uses orchestrators for their execution, and relies on existing standards. The approach is highly flexible and applies to not only workflow automation in single locations but also distributed workflows (e.g. for biomanufacturing). The final section presents an overview of the implementation-using the simple example of an assay based on a dilution, measurement, and data analysis workflow.

Genetic Parts and Enabling Tools for Biocircuit Design.

Synthetic biology aims to engineer biological systems for customized tasks through the bottom-up assembly of fundamental building blocks, which requires high-quality libraries of reliable, modular, and standardized genetic parts. To establish sets of parts that work well together, synthetic biologists created standardized part libraries in which every component is analyzed in the same metrics and context. Here we present a state-of-the-art review of the currently available part libraries for designing biocircuits and their gene expression regulation paradigms at transcriptional, translational, and post-translational levels in Escherichia coli. We discuss the necessary facets to integrate these parts into complex devices and systems along with the current efforts to catalogue and standardize measurement data. To better display the range of available parts and to facilitate part selection in synthetic biology workflows, we established biopartsDB, a curated database of well-characterized and useful genetic part and device libraries with detailed quantitative data validated by the published literature.

A novel optimization approach for bio-design of therapeutic compression stockings with pressure fit.

For physical-based compression therapeutic modalities, especially compression stockings (CSs), their pressure performances are necessarily evaluated by the standardized cylinder leg mannequins before biological applications. However, the insufficient pressure supply caused by morphological shape diversities between circular leg mannequins and irregular bio-bodies limits the clinical effectiveness and user compliance of CSs. Therefore, an operable and efficiency approach for optimization bio-design and digital development of CSs with enhanced compression performances needs to be proposed. The present study has adopted three-dimensional (3D) body scanning and reverse engineering technologies for lower limb cross-sectional geometric characterization and morphological classification. The irregularity of biological leg circumferential slices was determined and clustered as four levels relating to individual curvature variations. Sequentially, a new pressure prediction model was constructed through characterized geometric variations for bio-based bodies, then its acceptability was validated with good agreement by wearing trials (mean prediction accuracy was 2.53 ± 0.52 mmHg). Thus, the digital pressure reshaped development guidance was obtained based on the classified irregular levels and established pressure prediction models. Consequently, this study provides a novel reliable optimization bio-design solution for manufacturing of therapeutic compression textiles and facilitates the medical efficacy and precision of compression therapy in practical use.

From biomimicry to robotic co-creation: rethinking the boundaries between nature and technology.

This paper is an invitation to an interdisciplinary dialogue on new possibilities for integrating robotics, design, and nature. I ask: how can new cross-movements between bio-inspired science and design be fostered? How might we envision the future possible intersection between technology and nature? First, I recall key aspects of classical bioinspired engineering and highlight the role of nature in the emergence of technology. Second, I introduce a new approach to bioinspired engineering. In this approach, robots play an active role in design and construction, learning from material properties to form new shapes and thus reshaping design paradigms. The distinctive elements of this approach depart from classical nature-inspired engineering and foster a symbiotic relationship between technology and nature. I conclude by reflecting on the intersections of nature, technology, and design, and envisioning new avenues for interdisciplinary dialogue that foster collaboration and innovation among diverse bio-inspired disciplines.

Exhaustion of racing sperm in nature-mimicking microfluidic channels during sorting.

Fertilization is central to the survival and propagation of a species, however, the precise mechanisms that regulate the sperm's journey to the egg are not well understood. In nature, the sperm has to swim through the cervical mucus, akin to a microfluidic channel. Inspired by this, a simple, cost-effective microfluidic channel is designed on the same scale. The experimental results are supported by a computational model incorporating the exhaustion time of sperm.

Bluegrass Biodesign: Why an Integrated Biomedical Engineering Curriculum is Crucial for Medical Education.

Background Medical education often overlooks the significance of design and innovation literacy, resulting in a knowledge gap in undergraduate medical education (UME) regarding formal training in these areas. Incorporating innovation into UME's core curriculum is crucial as future physicians will encounter evolving technologies, and fostering a transdisciplinary approach can enable collaborative problem-solving and improve patient health outcomes. Methodology We developed a comprehensive medical biodesign curriculum focused on innovation, including problem identification, prototype testing, and product commercialization. Participants were selected based on applications, interviews, and diverse criteria. A survey was conducted before and after the program to assess students' biodesign experiences and knowledge, with data analyzed using descriptive statistics and paired t-tests. Results Of the 41 participants, 24 (58.5%) completed both pre- and post-program surveys. These five-point Likert surveys showed a significant shift from pre-program to responses demonstrating increased "comfort levels in explaining and applying biodesign principles" (p < 0.0001). Specifically, the "comfort level in taking a product to market" increased from 33% to 67% (p = 0.01), while the "comfort level in applying the biodesign process" increased from 29% to 92% (p < 0.0001). Moreover, 58.3% of participants expressed interest in continuing their current projects, and 70.8% of students stated feeling confident in generating ideas and solutions with their team members. Conclusions The medical biodesign curriculum demonstrated success in exposing undergraduate medical and engineering students to the concepts of medical innovation and biodesign. The program has led to a significant improvement in students' knowledge and comfort levels in applying the biodesign process and taking a product to market. The high level of interest and participation in the program highlight the need for incorporating innovative training in UME to foster creativity and prepare future physicians to contribute to the advancements in healthcare.

Bio-Producing Bacterial Cellulose Filaments through Co-Designing with Biological Characteristics.

The need for circular textiles has led to an interest in the production of biologically derived materials, generating new research into the bioproduction of textiles through design and interdisciplinary approaches. Bacterial cellulose has been produced directly from fermentation into sheets but not yet investigated in terms of producing filaments directly from fermentation. This leaves a wealth of material qualities unexplored. Further, by growing the material directly into filaments, production such as wet spinning are made redundant, thus reducing textile manufacturing steps. The aim of this study was to grow the bio-material, namely bacterial cellulose directly into a filament. This was achieved using a method of co-designing with the characteristics of biological materials. The method combines approaches of material-driven textile design and human-centred co-design to investigate co-designing with the characteristics of living materials for biological material production. The project is part of a wider exploration of bio-manufacturing textiles from waste. The practice-based approach brought together biological sciences and material design through a series of iterative experiments. This, in turn, resulted in designing with the inherent characteristics of bacterial cellulose, and by doing so filaments were designed to be fabricated directly from fermentation. In this investigation, creative exploration was encouraged within a biological laboratory space, showing how interdisciplinary collaboration can offer innovative alternative bioproduction routes for textile filament production.

Multiscale design of cell-free biologically active architectural structures.

Cell-free protein expression systems are here combined with 3D-printed structures to study the challenges and opportunities as biofabrication enters the spaces of architecture and design. Harnessing large-scale additive manufacturing of biological materials, we examined the addition of cell-free protein expression systems ("TXTL" i.e., biological transcription-translation machinery without the use of living cells) to printed structures. This allowed us to consider programmable, living-like, responsive systems for product design and indoor architectural applications. This emergent, pluripotent technology offers exciting potential in support of health, resource optimization, and reduction of energy use in the built environment, setting a new path to interactivity with mechanical, optical, and (bio) chemical properties throughout structures. We propose a roadmap towards creating healthier, functional and more durable systems by deploying a multiscale platform containing biologically-active components encapsulated within biopolymer lattices operating at three design scales: (i) supporting cell-free protein expression in a biopolymer matrix (microscale), (ii) varying material properties of porosity and strength within two-dimensional lattices to support biological and structural functions (mesoscale), and (iii) obtaining folded indoor surfaces that are structurally sound at the meter scale and biologically active (we label that regime macroscale). We embedded commercially available cell-free protein expression systems within silk fibroin and sodium alginate biopolymer matrices and used green fluorescent protein as the reporter to confirm their compatibility. We demonstrate mechanical attachment of freeze-dried bioactive pellets into printed foldable fibrous biopolymer lattices showing the first steps towards modular multiscale fabrication of large structures with biologically active zones. Our results discuss challenges to experimental setup affecting expression levels and show the potential of robust cell-free protein-expressing biosites within custom-printed structures at scales relevant to everyday consumer products and human habitats.

Teaching Principles of Medical Innovation and Entrepreneurship Through Hackathons: Case Study and Qualitative Analysis.

BACKGROUND: Innovation and entrepreneurship training are increasingly recognized as being important in medical education. However, the lack of faculty comfort with the instruction of these concepts as well as limited scholarly recognition for this work has limited the implementation of curricula focused on these skills. Furthermore, this lack of familiarity limits the inclusion of practicing physicians in health care innovation, where their experience is valuable. Hackathons are intense innovation competitions that use gamification principles to increase comfort with creative thinking, problem-solving, and interpersonal collaboration, but they require further exploration in medical innovation. OBJECTIVE: To address this, we aimed to design, implement, and evaluate a health care hackathon with 2 main goals: to improve emergency physician familiarity with the principles of health care innovation and entrepreneurship and to develop innovative solutions to 3 discrete problems facing emergency medicine physicians and patients. METHODS: We used previously described practices for conducting hackathons to develop and implement our hackathon (HackED!). We partnered with the American College of Emergency Physicians, the Stanford School of Biodesign, and the Institute of Design at Stanford (d.school) to lend institutional support and expertise in health care innovation to our event. We determined a location, time frame, and logistics for the competition and settled on 3 use cases for teams to work on. We planned to explore the learning experience of participants within a pragmatic paradigm and complete an abductive thematic analysis using data from a variety of sources. RESULTS: HackED! took place from October 1-3, 2022. In all, 3 teams developed novel solutions to each of the use cases. Our investigation into the educational experience of participants suggested that the event was valuable and uncovered themes suggesting that the learning experience could be understood within a framework from entrepreneurship education not previously described in relation to hackathons. CONCLUSIONS: Health care hackathons appear to be a viable method of increasing physician experience with innovation and entrepreneurship principles and addressing complex problems in health care. Hackathons should be considered as part of educational programs that focus on these concepts.

Mycelium-Based Composite Materials: Study of Acceptance.

Mycelium-based composites (MBCs) are alternative biopolymers for designing sustainable furniture and other interior elements. These innovative biocomposites have many ecological advantages but present a new challenge in aesthetics and human product acceptance. Grown products, made using living mycelium and lignocellulosic substrates, are porous, have irregular surfaces and have irregular coloring. The natural origin of these types of materials and the fear of fungus can be a challenge. This research investigated the level of human acceptance of the new material. Respondents were students of architecture who can be considered as people involved in interior design and competent in the design field. Research has been performed on the authors' prototype products made from MBCs. Three complementary consumer tests were performed. The obtained results measured the human reactions and demonstrated to which extents products made of MBCs were "likeable" and their nonobvious aesthetics were acceptable to the public. The results showed that MBC materials generally had a positive or not-negative assessment. The responses after the pairwise comparison of the MBC with wall cladding samples pointed out the advantage of ceramic reference material above the MBC based on an overall assessment. The respondents also believed that the chamotte clay cladding would be easier to fit into the aesthetics of a modern interior and would in better accordance with its style. Although the MBC was less visually appealing, the respondents nevertheless found it more interesting, original, and environmentally friendly. The experiments suggested that the respondents had double standards regarding MBCs. MBCs were generally accepted as ecological, but not in their own homes. All of these results support current and future applications of MBCs for manufacturing items where enhanced aesthetics are required.