Spinal segmental myoclonus following spinal surgery.

A 44-year-old male was admitted with L5/S1 spondylodiscitis complicated by a posterior epidural abscess that was compressing the thecal sac with severe narrowing of the canal and compression of the cauda equine. He underwent computed tomography (CT) guided drainage followed by L5/S1 decompression laminectomy and was started on a 6-week course of intravenous antibiotics with good response. He remained well and afebrile with inflammatory markers showing improvement. During this period, he developed intermittent myoclonic movements of right lower limb with severe pain over the back radiating to the gluteal region which hindered his rehabilitation potential. He was diagnosed with spinal segmental myoclonus based on clinical findings and history of recent spinal surgery. He was successfully treated with a course of clonazepam and continues to make functional improvements during his rehabilitation program.

Internal Medicine Residents' Attitudes Toward Simulated Depressed Cardiac Patients During an Objective Structured Clinical Examination: A Randomized Study.

BACKGROUND: Physician biases toward mental conditions such as depression have been shown to adversely affect medical outcomes. OBJECTIVE: To explore the relationship between residents' explicit bias toward depressed patients and their clinical skills on a cardiac case during an objective structured clinical exam (OSCE). DESIGN: Prospective parallel randomized controlled study. PARTICIPANTS: One hundred eighty-five internal medicine residents from three residency programs in two states. INTERVENTION: During October-November 2015, residents were randomized to either a depressed or non-depressed standardized patient (SP) presenting with acute chest pain. MAIN MEASURES: The Medical Condition Regard Scale (MCRS) assessed residents' explicit bias toward patients with depression. Their clinical skills (history-taking, physical examination, patient counseling, patient-physician interaction (PPI), differential diagnosis, and workup plan) and facial expressions were rated during an OSCE. KEY RESULTS: No significant relationships were found between resident explicit bias and clinical skill measurements. Residents who examined the depressed SP scored lower, on average, on history-taking (t [183] = -2.77, p < 0.01, Cohen's d = 0.41) and higher on PPI (t [183] = 2.24, p < 0.05, Cohen's d = 0.33) than residents examining the non-depressed SP. There were no differences, on average, between stations on physical examination, counseling, correct diagnosis, workup plan, or overall SP satisfaction. Facial recognition software demonstrated that residents with a non-depressed SP had more neutral expressions than depressed-SP residents (t [133] = -2.46, p < 0.05, Cohen's d = 0.46), and residents with a depressed SP had more disgusted expressions than non-depressed-SP residents (t [83.52] = 2.10, p < 0.05, Cohen's d = 0.28). CONCLUSIONS: Extrinsic bias did not predict OSCE performance in this study. Some differences were noted in the OSCE performance between the two stations. Further study is needed to examine the effects of patient mental health conditions on physician examination procedures, diagnostic behaviors, and patient outcomes.

An Exploration of Residents' Implicit Biases Towards Depression-a Pilot Study.

BACKGROUND: Implicit attitudes are outside of conscious awareness and are thought to affect automatic responses outside of one's deliberate control, with the potential to impact physician-patient relationships. OBJECTIVE: To measure the nature and extent of implicit biases towards depression in internal medicine and psychiatry residents. DESIGN: Descriptive and comparative study. PARTICIPANTS: Fifty-one residents from three internal medicine programs and 35 residents from three psychiatry programs located in two states. INTERVENTIONS: Participants were sent a link to voluntarily participate in four online implicit association tests. Residents' identities were anonymous. MAIN MEASURES: Four implicit association tests to measure the association of (1) attitude (good/bad), (2) permanence, (3) controllability, and (4) etiology with depression/physical illness. KEY RESULTS: Internal medicine residents demonstrated a significant association between depression and negative attitudes (t(38) = 6.01, p < .001, Cohen's d = .95), uncontrollability (t(35) = 4.80, p < .001, Cohen's d = .79), temporariness (t(37) = 2.94, p = .006, Cohen's d = .48), and a psychologic etiology (t(1) = 6.91, p < .001, Cohen's d = 1.24). Psychiatry residents only demonstrated an association between depression and a psychologic etiology (t(2) = 4.79, p < .001, Cohen's d = 4.5). When comparing the two specialties, internal medicine and psychiatry differed on two of the IATs. Internal medicine residents were more likely to associate negative attitudes with depression than psychiatry residents (t(63) = 4.66, p < .001, Cohen's d = 1.18) and to associate depression with being uncontrollable (t(57) = 3.17, p = .002, Cohen's d = .81). CONCLUSIONS: Internal medicine residents demonstrated biases in their attitudes towards depression and significantly differed in some areas from psychiatry residents. This pilot study needs to be replicated to confirm our findings and further work needs to be done to determine the effect of these attitudes on the provision of clinical care.

Position, Orientation and Velocity Detection of Unmanned Underwater Vehicles (UUVs) Using an Optical Detector Array.

This paper presents a proof-of-concept optical detector array sensor system to be used in Unmanned Underwater Vehicle (UUV) navigation. The performance of the developed optical detector array was evaluated for its capability to estimate the position, orientation and forward velocity of UUVs with respect to a light source fixed in underwater. The evaluations were conducted through Monte Carlo simulations and empirical tests under a variety of motion configurations. Monte Carlo simulations also evaluated the system total propagated uncertainty (TPU) by taking into account variations in the water column turbidity, temperature and hardware noise that may degrade the system performance. Empirical tests were conducted to estimate UUV position and velocity during its navigation to a light beacon. Monte Carlo simulation and empirical results support the use of the detector array system for optics based position feedback for UUV positioning applications.

Improving umbilical cord blood processing to increase total nucleated cell count yield and reduce cord input wastage by managing the consequences of input variation.

BACKGROUND AIMS: With the rising use of umbilical cord blood (UCB) as an alternative source of hematopoietic stem cells, storage inventories of UCB have grown, giving rise to genetically diverse inventories globally. In the absence of reliable markers such as CD34 or counts of colony-forming units, total nucleated cell (TNC) counts are often used as an indicator of potency, and transplant centers worldwide often select units with the largest counts of TNC. As a result, cord blood banks are driven to increase the quality of stored inventories by increasing the TNC count of products stored. However, these banks face challenges in recovering consistent levels of TNC with the use of the standard protocols of automated umbilical cord processing systems, particularly in the presence of input variation both of cord blood volume and TNC count, in which it is currently not possible to process larger but useable UCB units with consequent losses in TNC. METHODS: This report addresses the challenge of recovering consistently high TNC yields in volume reduction by proposing and validating an alternative protocol capable of processing a larger range of units more reliably. RESULTS: This work demonstrates improvements in plastic ware and tubing sets and in the recovery process protocol with consequent productivity gains in TNC yield and a reduction in standard deviation. CONCLUSIONS: This work could pave the way for cord blood banks to improve UCB processing and increase efficiency through higher yields and lower costs.

A comparison of medical students' learning approaches between the first and fourth years.

OBJECTIVES: We hypothesized that medical students exposed to a case-based curriculum in years 1 and 2 and clinical cases in the year 3 clerkship would demonstrate a longitudinal increase in the deep approach to learning and a decrease in the surface apathetic approach. METHODS: A cohort of first-year medical students completed the Approaches and Study Skills Inventory for Students at the beginning of their first term and again at the beginning of their fourth year. Approaches and Study Skills Inventory for Students scores were aggregated into three main learning approach scales: deep, strategic, and surface apathetic. RESULTS: On average, deep and strategic scores did not significantly change between years 1 and 4, but the surface apathetic mean score decreased as a result of lower syllabus boundness and fear of failure subscale scores. Effect sizes were small (d = 0.30, 0.34, respectively). CONCLUSIONS: The deep approach to learning is a complex process and did not change in our students after 3 years of medical school, even though a case-based curriculum was believed to foster deeper learning. By the end of year 3, our students were, on average, less bound to syllabi and feared failure less.

Assessing 3rd year medical students' interprofessional collaborative practice behaviors during a standardized patient encounter: A multi-institutional, cross-sectional study.

BACKGROUND: To understand how third-year medical student interprofessional collaborative practice (IPCP) is affected by self-efficacy and interprofessional experiences (extracurricular experiences and formal curricula). METHODS: The authors measured learner IPCP using an objective structured clinical examination (OSCE) with a standardized nurse (SN) and standardized patient (SP) during a statewide clinical performance examination. At four California medical schools from April to August 2012, SPs and SNs rated learner IPCP (10 items, range 0-100) and patient-centered communication (10 items, range 0-100). Post-OSCE, students reported their interprofessional self-efficacy (16 items, 2 factors, range 1-10) and prior extracurricular interprofessional experiences (3 items). School representatives shared their interprofessional curricula during guided interviews. RESULTS: Four hundred sixty-four of 530 eligible medical students (88%) participated. Mean IPCP performance was 79.6 ± 14.1 and mean self-efficacy scores were 7.9 (interprofessional teamwork) and 7.1 (interprofessional feedback and evaluation). Seventy percent of students reported prior extracurricular interprofessional experiences; all schools offered formal interprofessional curricula. IPCP was associated with self-efficacy for interprofessional teamwork (ß = 1.6, 95% CI [0.1, 3.1], p = 0.04) and patient-centered communication (ß = 12.5, 95% CI [2.7, 22.3], p = 0.01). CONCLUSIONS: Medical student IPCP performance was associated with self-efficacy for interprofessional teamwork and patient-centered communication. Increasing interprofessional opportunities that influence medical students' self-efficacy may increase engagement in IPCP.

Measurement of perceptions of educational environment in evidence-based medicine.

In recent years, there has been a renewed interest in measuring perceptions regarding different aspects of the medical educational environment. A reliable tool was developed for measuring perceptions of the educational environment as it relates to evidence-based medicine as part of a multicountry randomised controlled trial to evaluate the effectiveness of a clinically integrated evidence-based medicine course. Participants from 10 specialties completed the questionnaire. A working dataset of 518 observations was available. Two independent subsets of data were created for conducting an exploratory factor analysis (n=244) and a confirmatory factor analysis (n=274), respectively. The exploratory factor analysis yielded five 67-item definitive instruments, with five to nine dimensions; all resulted in acceptable explanations of the total variance (range 56.6-65.9%). In the confirmatory factor analysis phase, all goodness of-fit measures were acceptable for all models (root mean square error of approximation ≤ 0.047; comparative fit index ≥ 0.980; normed χ(2) ≤ 1.647; Bentler-Bonett normed fit index ≥ 0.951). The authors selected the factorisation with seven dimensions (factor-7 instrument) as the most useful on pragmatic grounds and named it Evidence-Based Medicine Educational Environment Measure 67 (EBMEEM-67). Cronbach's α for subscales ranged between 0.81 and 0.93. The subscales are: 'Knowledge and learning materials'; 'Learner support'; 'General relationships and support'; 'Institutional focus on EBM'; 'Education, training and supervision'; 'EBM application opportunities'; and 'Affirmation of EBM environment'. The EBMEEM-67 can be a useful diagnostic and benchmarking tool for evaluating the perceptions of residents of the environment in which evidence-based medicine education takes place.

Commercialization of skin substitutes for third-degree burn wounds.

Technological advances have increasingly provided more and better treatment options for patients with severe burns. Here, we provide a bird's-eye view of the product development process for third-degree burn wounds with considerations of the critical interaction with regulatory bodies, existing technological gaps, and future directions for skin substitutes.

Current status and perspectives on stem cell-based therapies undergoing clinical trials for regenerative medicine: case studies.

BACKGROUND: Apart from haematopoietic stem cell transplantation for haematological disorders many stem cell-based therapies are experimental. However, with only 12 years between human embryonic stem cell isolation and the first clinical trial, development of stem cell products for regenerative medicine has been rapid and numerous clinical trials have begun to investigate their therapeutic potential. SOURCE OF DATA: This review summarizes key clinical trial data, current and future perspectives on stem cell-based products undergoing clinical trials, based on literature search and author research. AREAS OF AGREEMENT: It is widely recognized that the ability to stimulate stem cell differentiation into specialized cells for use as cellular therapies will revolutionize health care and offer major hope for numerous diseases for which there are limited or no therapeutic options. AREAS OF CONTROVERSY: Stem cell-based products are unique and cover a large range of disorders to be treated; therefore, there is significant potential for variation in cell source, type, processing manipulation, the bioprocessing approach and scalability, the cost and purity of manufacture, final product quality and mode of action. As such there are gaps in regulatory and manufacturing frameworks and technologies, only a small number of products are currently within late phase clinical trials and few products have achieved commercialization. GROWING POINTS: Recent developments are encouraging acceleration through the difficulties encountered en route to clinical trials and commercialization of stem cell therapies. AREAS TIMELY FOR DEVELOPING RESEARCH: The field is growing year on year with the first clinical trial using induced pluripotent stem cells anticipated by end 2013.

The relationship between medical students' learning approaches and performance on a summative high-stakes clinical performance examination.

BACKGROUND: A learning approach embeds the intention of the student when starting a task and the learning processes and strategies used to carry out a task. Student approaches to learning have been categorized as deep, strategic, and surface. AIM: To explore the relationships among medical students' learning approaches, gender, and performance on a summative high-stakes clinical performance examination (CPX). METHODS: We measured medical students' learning approaches at the beginning of year four using the Approaches and Study Skills Inventory for Students and compared results with CPX scores. RESULTS: Student scores in the top two quartiles of the CPX were significantly higher on the deep approach than student CPX scores in the bottom quartile, and student scores in the bottom quartile of the CPX were significantly higher on the surface approach than scores for the other three CPX quartiles. CPX patient-physician interaction scores showed a significant positive correlation with deep approach scores, and CPX overall patient satisfaction scores showed a significant positive correlation with deep and strategic approach scores. Surface approach scores correlated negatively with all CPX score categories. CONCLUSION: Approach to learning was associated with performance on a high-stakes CPX.

Effectiveness of a clinically integrated e-learning course in evidence-based medicine for reproductive health training: a randomized trial.

CONTEXT: For evidence-based practice to embed culturally in the workplace, teaching of evidence-based medicine (EBM) should be clinically integrated. In low-middle-income countries (LMICs) there is a scarcity of EBM-trained clinical tutors, lack of protected time for teaching EBM, and poor access to relevant databases in languages other than English. OBJECTIVE: To evaluate the effects of a clinically integrated e-learning EBM course incorporating the World Health Organization (WHO) Reproductive Health Library (RHL) on knowledge, skills, and educational environment compared with traditional EBM teaching. DESIGN, SETTING, AND PARTICIPANTS: International cluster randomized trial conducted between April 2009 and November 2010 among postgraduate trainees in obstetrics-gynecology in 7 LMICs (Argentina, Brazil, Democratic Republic of the Congo, India, Philippines, South Africa, Thailand). Each training unit was randomized to an experimental clinically integrated course consisting of e-modules using the RHL for learning activities and trainee assessments (31 clusters, 123 participants) or to a control self-directed EBM course incorporating the RHL (29 clusters, 81 participants). A facilitator with EBM teaching experience was available at all teaching units. Courses were administered for 8 weeks, with assessments at baseline and 4 weeks after course completion. The study was completed in 24 experimental clusters (98 participants) and 22 control clusters (68 participants). MAIN OUTCOME MEASURES: Primary outcomes were change in EBM knowledge (score range, 0-62) and skills (score range, 0-14). Secondary outcome was educational environment (5-point Likert scale anchored between 1 [strongly agree] and 5 [strongly disagree]). RESULTS: At baseline, the study groups were similar in age, year of training, and EBM-related attitudes and knowledge. After the trial, the experimental group had higher mean scores in knowledge (38.1 [95% CI, 36.7 to 39.4] in the control group vs 43.1 [95% CI, 42.0 to 44.1] in the experimental group; adjusted difference, 4.9 [95% CI, 2.9 to 6.8]; P < .001) and skills (8.3 [95% CI, 7.9 to 8.7] vs 9.1 [95% CI, 8.7 to 9.4]; adjusted difference, 0.7 [95% CI, 0.1 to 1.3]; P = .02). Although there was no difference in improvement for the overall score for educational environment (6.0 [95% CI, -0.1 to 12.0] vs 13.6 [95% CI, 8.0 to 19.2]; adjusted difference, 9.6 [95% CI, -6.8 to 26.1]; P = .25), there was an associated mean improvement in the domains of general relationships and support (-0.5 [95% CI, -1.5 to 0.4] vs 0.3 [95% CI, -0.6 to 1.1]; adjusted difference, 2.3 [95% CI, 0.2 to 4.3]; P = .03) and EBM application opportunities (0.5 [95% CI, -0.7 to 1.8] vs 2.9 [95%, CI, 1.8 to 4.1]; adjusted difference, 3.3 [95% CI, 0.1 to 6.5]; P = .04). CONCLUSION: In a group of LMICs, a clinically integrated e-learning EBM curriculum in reproductive health compared with a self-directed EBM course resulted in higher knowledge and skill scores and improved educational environment. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12609000198224.

A Call to Action From the California Consortium for the Assessment of Clinical Competence: Making the Case for Regional Collaboration.

The discontinuation of the United States Medical Licensing Examination Step 2 Clinical Skills Examination emphasizes the need for other reliable standardized assessments of medical student clinical skills. For 30 years, the California Consortium for the Assessment of Clinical Competence (CCACC) has collaborated in the development of clinical skills assessments and has become a valuable resource for clinicians, standardized patient educators, psychometricians, and medical educators. There are many merits to strong multi-institutional partnerships, including the integration of data across multiple schools to provide feedback to both students and curricula, pooled test performance statistics for analysis and quality assurance, shared best practices and resources, individual professional development, and opportunities for research and scholarship. The infrastructure of the CCACC allows member schools to adapt to a changing medical landscape, from emerging trends in clinical medicine to the limitations imposed by a global pandemic. In the absence of a national examination, there is now a greater need for all medical schools to develop a comprehensive, dynamic, and psychometrically sound assessment that accurately evaluates clinical skills. Medical schools working together in regional consortia have the opportunity to create and implement innovative and robust assessments that evaluate a wide range of clinical skills, ensure that medical students have met an expected level of clinical competency before graduation, and provide a framework that contributes to ongoing efforts for the development of new national clinical skills standards.

In-situ scalable manufacturing of Epstein-Barr virus-specific T-cells using bioreactor with an expandable culture area (BECA).

The ex-vivo expansion of antigen-specific T-cells for adoptive T-cell immunotherapy requires active interaction between T-cells and antigen-presenting cells therefore culture density and environment become important variables to control. Maintenance of culture density in a static environment is traditionally performed by the expansion of the culture area through splitting of culture from a single vessel into multiple vessels-a highly laborious process. This study aims to validate the use and efficacy of a novel bioreactor, bioreactor with an expandable culture area-dual chamber (BECA-D), that was designed and developed with a cell chamber with expandable culture area (12-108 cm2) and a separate media chamber to allow for in-situ scaling of culture with maintenance of optimum culture density and improved nutrient and gas exchange while minimizing disturbance to the culture. The performance of BECA-D in the culture of Epstein-Barr virus-specific T-cells (EBVSTs) was compared to the 24-well plate. BECA-D had 0.9-9.7 times the average culture yield of the 24-well plates across 5 donor sets. BECA-D was able to maintain the culture environment with relatively stable glucose and lactate levels as the culture expanded. This study concludes that BECA-D can support the culture of ex-vivo EBVSTs with lower manufacturing labour and time requirements compared to the use of the 24-well plate. BECA-D and its adaptation into a closed system with an automated platform (currently being developed) provides cell therapy manufacturers and developers with a closed scale-out solution to producing adoptive cell therapy for clinical use.

Effect of feedback from standardized patients on medical students' performance and perceptions of the neurological examination.

BACKGROUND: Feedback can have a powerful influence on the performance of learners, and has traditionally been provided by faculty. AIM: This study set out to explore whether feedback from a standardized patient (SP) can improve students' performance of the neurological examination. METHODS: A randomized controlled design was used with final year medical students. The control group did not receive any feedback. The intervention groups received either written feedback or a combination of written and verbal feedback. A written test was given prior to the intervention to assess comparability of the three groups. Pretest and post-test scores on the neurological examination were compared. Attitudinal questionnaires were administered at the time of the posttest, and 6 months later. RESULTS: Students receiving feedback from the SPs had significantly greater scores on the posttest than the control group. In the intervention groups, students receiving both verbal and written feedback scored significantly higher than those who received only written feedback. More positive perceptions of learning outcomes and the value of SP feedback were noted in the intervention groups. CONCLUSION: SP feedback was associated with a significant increase in student scores on the neurological examination, as well as more favorable perceptions of the experience.

Assessing patient-centered care: one approach to health disparities education.

BACKGROUND: Patient-centered care has been described as one approach to cultural competency education that could reduce racial and ethnic health disparities by preparing providers to deliver care that is respectful and responsive to the preferences of each patient. In order to evaluate the effectiveness of a curriculum in teaching patient-centered care (PCC) behaviors to medical students, we drew on the work of Kleinman, Eisenberg, and Good to develop a scale that could be embedded across cases in an objective structured clinical examination (OSCE). OBJECTIVE: To compare the reliability, validity, and feasibility of an embedded patient-centered care scale with the use of a single culturally challenging case in measuring students' use of PCC behaviors as part of a comprehensive OSCE. METHODS: A total of 322 students from two California medical schools participated in the OSCE as beginning seniors. Cronbach's alpha was used to assess the internal consistency of each approach. Construct validity was addressed by establishing convergent and divergent validity using the cultural challenge case total score and OSCE component scores. Feasibility assessment considered cost and training needs for the standardized patients (SPs). RESULTS: Medical students demonstrated a moderate level of patient-centered skill (mean = 63%, SD = 11%). The PCC Scale demonstrated an acceptable level of internal consistency (alpha = 0.68) over the single case scale (alpha = 0.60). Both convergent and divergent validities were established through low to moderate correlation coefficients. DISCUSSION: The insertion of PCC items across multiple cases in a comprehensive OSCE can provide a reliable estimate of students' use of PCC behaviors without incurring extra costs associated with implementing a special cross-cultural OSCE. This approach is particularly feasible when an OSCE is already part of the standard assessment of clinical skills. Reliability may be increased with an additional investment in SP training.

A cluster randomized controlled trial to evaluate the effectiveness of the clinically integrated RHL evidence -based medicine course.

BACKGROUND AND OBJECTIVES: Evidence-based health care requires clinicians to engage with use of evidence in decision-making at the workplace. A learner-centred, problem-based course that integrates e-learning in the clinical setting has been developed for application in obstetrics and gynaecology units. The course content uses the WHO reproductive health library (RHL) as the resource for systematic reviews. This project aims to evaluate a clinically integrated teaching programme for incorporation of evidence provided through the WHO RHL. The hypothesis is that the RHL-EBM (clinically integrated e-learning) course will improve participants' knowledge, skills and attitudes, as well as institutional practice and educational environment, as compared to the use of standard postgraduate educational resources for EBM teaching that are not clinically integrated. METHODS: The study will be a multicentre, cluster randomized controlled trial, carried out in seven countries (Argentina, Brazil, Democratic Republic of Congo, India, Philippines, South Africa, Thailand), involving 50-60 obstetrics and gynaecology teaching units. The trial will be carried out on postgraduate trainees in the first two years of their training. In the intervention group, trainees will receive the RHL-EBM course. The course consists of five modules, each comprising self-directed e-learning components and clinically related activities, assignments and assessments, coordinated between the facilitator and the postgraduate trainee. The course will take about 12 weeks, with assessments taking place pre-course and 4 weeks post-course. In the control group, trainees will receive electronic, self-directed EBM-teaching materials. All data collection will be online.The primary outcome measures are gain in EBM knowledge, change in attitudes towards EBM and competencies in EBM measured by multiple choice questions (MCQs) and a skills-assessing questionniare administered eletronically. These questions have been developed by using questions from validated questionnaires and adapting them to the current course. Secondary outcome measure will be educational environment towards EBM which will be assessed by a specifically developed questionnaire. EXPECTED OUTCOMES: The trial will determine whether the RHL EBM (clinically integrated e-leraning) course will increase knowledge, skills and attitudes towards EBM and improve the educational environment as compared to standard teaching that is not clinically integrated. If effective, the RHL-EBM course can be implemented in teaching institutions worldwide in both, low-and middle income countries as well as industrialized settings. The results will have a broader impact than just EBM training because if the approach is successful then the same educational strategy can be used to target other priority clinical and methodological areas. TRIAL REGISTRATION: ACTRN12609000198224.

Commercialization of Organoids.

Organoids have been successfully exploited for drug screening, disease modeling, pathogenesis, and regenerative medicine. Herein, we discuss the progress achieved in the commercialization of organoids in the last few years. We further elaborate on the concept of organoid biobank and highlight ethical and regulatory issues surrounding organoid research and commercialization.

Decellularization systems and devices: State-of-the-art.

Extracellular matrix (ECM) is a natural biomaterial scaffold that provides biochemical and structural support to its surrounding cells, forming tissue and respective organs. These ECM proteins can be extracted from organs and tissues through decellularization, which is the process of removing cellular content and nuclear material from the organs to obtain decellularized ECM (dECM). dECM is a versatile and functional biomaterial that can be used as the base component of bioinks for rebuilding tissue and organs. Intact dECM of whole organs can be used as a scaffold for recellularization with human stem cells to produce a functioning organ. As decellularization is a relatively new lab process, the associated technologies and devices are largely non-standardized and only available in small, lab-specific scales. Additionally, there is a lack of standardized protocols to analyze the quality and consistency of harvested dECM for medical applications. This review discusses the relevant decellularization systems and devices currently available to facilitate further development of this process for larger scales with the intention to commercialize dECM materials. STATEMENT OF SIGNIFICANCE: Extracellular matrix (ECM) is a natural cocktail of biomaterials that provides biochemical and structural support to its surrounding cells. ECM proteins are extracted from organs and tissues through decellularization. Being a versatile and functional biomaterial, decellularized extracellular matrix (dECM) is being used as base component of bioinks/hydrogels for rebuilding of tissue and organ constructs. Decellularization is a relatively new lab process with associated technologies/devices being largely non-standardized and only available in lab-specific scales. We discuss categories of decellularization systems and devices for the first time being used in academic and commercial settings. We highlight inherent challenges with the current systems and suggest possible solutions. We comment on further development of these processes for large-scale and commercial applications of dECM.

In situ bioprinting - Bioprinting from benchside to bedside?

Bioprinting technologies have been advancing at the convergence of automation, digitalization, and new tissue engineering (TE) approaches. In situ bioprinting may be favored during certain situations when compared with the conventional in vitro bioprinting when de novo tissues are to be printed directly on the intended anatomical location in the living body. To date, few attempts have been made to fabricate in situ tissues, which can be safely arrested and immobilized while printing in preclinical living models. In this review, we have explained the need and utility for in situ bioprinting with regard to the conventional bioprinting approach. The two main in situ bioprinting approaches, namely, robotic arm and handheld approaches, have been defined and differentiated. The various studies involving in situ fabrication of skin, bone, and cartilage tissues have been elucidated. Finally, we have also discussed the advantages, challenges, and the prospects in the field of in situ bioprinting modalities in line with parallel technological advancements. STATEMENT OF SIGNIFICANCE: In situ bioprinting may be favored during certain situations when compared with the conventional in vitro bioprinting when tissues are to be fabricated or repaired directly on the intended anatomical location in the living body, using the body as a bioreactor. However, the technology requires a lot more improvement to fabricate complex tissues in situ, which could eventually be possible through the multi-disciplinary innovations in tissue engineering. This review explains the need and utility and current approaches by handheld and robotic modes for in situ bioprinting. The latest studies involving in situ fabrication of skin, bone, and cartilage tissues have been elucidated. The review also covers the background studies, advantages, technical and ethical challenges, and possible suggestions for future improvements.