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Microtia and anotia are congenital auricular anomalies that negatively impact the psychosocial development of those affected. Because auricular cartilage is a type of elastic cartilage that lacks regenerative capacity, any notable defect in its structure requires a surgical approach to reconstructing the auricle. While there are several reconstructive options available between alloplastic and prosthetic implants, autologous rib cartilage grafts remain the most commonly used treatment modality. Still, this widely used technique is accompanied by significant patient discomfort in a young child and carries additional risks secondary to the traumatic process of rib cartilage extraction, such as pneumothorax and chest wall deformities, and the final esthetic results may not be ideal. To circumvent these limitations, tissue engineering approaches have been used to create a realistic-looking ear that mirrors the complex anatomy of the normal ear. This article reviews the biochemical and biomechanical properties of human auricular cartilage as they relate to design criteria. In addition, a variety of cell sources, biocompatible scaffolds, scaffold-free techniques, and mechanical and biological stimuli are discussed. This review aims to identify knowledge gaps in the literature related to auricular cartilage characteristics and make recommendations to drive the field of auricular tissue engineering.
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OBJECTIVE: Bioscaffolds for treating soft tissue defects have limitations. As a bioscaffold, allograft adipose matrix (AAM) is a promising approach to treat soft tissue defects. Previously, we revealed that combining superficial adipose fascia matrix with AAM, components of the hypodermis layer of adipose tissue, improved volume retention, adipogenesis, and angiogenesis in rats 8 weeks after it was implanted compared with AAM alone. Here, we modified the fascia matrix and AAM preparation, examined the tissue over 18 weeks, and conducted a deeper molecular investigation. We hypothesized that the combined matrices created a better scaffold by triggering angiogenesis and proregenerative signals. METHODS: Human AAM and fascia matrix were implanted (4 [1 mL] implants/animal) into the dorsum of male Fischer rats (6-8 weeks old; ~140 g) randomly as follows: AAM, fascia, 75/25 (AAM/fascia), 50/50, and 50/50 + hyaluronic acid (HA; to improve extrudability) (n = 4/group/time point). After 72 hours, as well as 1, 3, 6, 9, 12, and 18 weeks, graft retention was assessed by a gas pycnometer. Adipogenesis (HE), angiogenesis (CD31), and macrophage infiltration (CD80 and CD163) were evaluated histologically at all time points. The adipose area and M1/M2 macrophage ratio were determined using ImageJ. RNA sequencing (RNA-seq) and bioinformatics were conducted to evaluate pathway enrichments. RESULTS: By 18 weeks, the adipose area was 2365% greater for 50/50 HA (281.6 ± 21.6) than AAM (11.4 ± 0.9) (P < 0.001). The M1/M2 macrophage ratio was significantly lower for 50/50 HA (0.8 ± 0.1) than AAM (0.9 ± 0.1) at 6 weeks (16%; P < 0.05). This inversely correlated with adipose area (r = -0.6; P > 0.05). The RNA-seq data revealed that upregulated adipogenesis, angiogenesis, and macrophage-induced tissue regeneration genes were temporally different between the groups. CONCLUSIONS: Combining the fascia matrix with AAM creates a bioscaffold with an improved retention volume that supports M2 macrophage-mediated angiogenesis and adipogenesis. This bioscaffold is worthy of further investigation.
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Roedores , Engenharia Tecidual , Humanos , Masculino , Ratos , Animais , Obesidade , Fáscia , Tecido Adiposo , AloenxertosRESUMO
PURPOSE: Currently, no treatment corrects the contractile nature of Dupuytren myofibroblasts (DMFs) or prevents recurrence following surgery. Antifibrotic and proadipogenic growth factors are released when adipose-derived stem cells (ASCs) are cultured with platelet-rich plasma (PRP), a platelet concentration from whole blood. Reprograming myofibroblasts into adipocytes via growth factors is proposed as a powerful potential tool to target fibrosis. We aimed to assess whether the combination of ASCs and PRP reprograms DMFs into adipocytes in vitro and alters their contractile nature in vivo. METHODS: Normal human dermal fibroblasts (NHDFs) and DMFs from Dupuytren patients were isolated and cocultured with ASCs and PRP either alone or together. Adipocytes were detected by Oil Red O and perilipin staining. DMFs and NHDFs were transplanted into the forepaws of rats (Rowett Nude [rnu/rnu]) and treated with saline, PRP+ASCs, or collagenase Clostridium histolyticum (clinical comparison) 2 months later. After 2 weeks, the tissue was harvested and subjected to Masson trichrome staining, and collagen I and III and alpha-smooth muscle actin detection by immunohistochemistry. RESULTS: Myofibroblasts transform into adipocytes upon coculture with PRP+ASCs. DMFs show increased alpha-smooth muscle actin expression in vivo compared with NHDFs, which is significantly decreased after PRP+ASCs and collagenase Clostridium histolyticum treatments. DMFs induce collagen I and III expressions in rat paws compared with NHDFs, with a type III to I ratio increase. Treatment with PRP+ASC reduced the ratio, but collagenase Clostridium histolyticum did not. CONCLUSIONS: Treating DMFs with PRP+ASCs provides factors that induce myofibroblast to adipocyte transformation. This treatment reduces the contractile phenotype and fibrosis markers in vivo. Future studies should detail the mechanism of this conversion. CLINICAL RELEVANCE: The combination of PRP and ASCs to induce the differentiation of DMFs into adipocytes may serve to limit surgery to a percutaneous contracture release and biological injection, rather than a moderate or radical fasciectomy, and reduce the recurrence of Dupuytren contracture.
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Contratura de Dupuytren , Humanos , Animais , Ratos , Contratura de Dupuytren/terapia , Miofibroblastos , Colagenase Microbiana , Actinas , Colágeno Tipo IRESUMO
OBJECTIVE: This review aims to evaluate the effectiveness of the two most commonly used oxygen delivery methods for the treatment of thermal burn wound healing: hyperbaric oxygen therapy (HBOT) and topical oxygen therapy (TOT). METHOD: The PubMed database was searched for articles discussing the use of HBOT or TOT in the treatment of thermal burns. RESULTS: The search yielded 43,406 articles, of which 28 (23 HBOT, 5 TOT) met the inclusion criteria. Both experimental and clinical studies have demonstrated conflicting results after treating thermal burns with HBOT or TOT. Overall, 14/23 studies demonstrated positive results for HBOT on the healing of burn wounds and associated complications, such as oedema and pain. Findings from these studies showed it can reduce morbidity and mortality in certain high-risk groups such as those with diabetes or extensive burns. Although the five studies (one human and four animal trials) reviewing TOT showed promising outcomes, this therapeutic modality has not been well investigated. CONCLUSION: Therapeutic use of HBOT in thermal burns has been popular in the past but its use remains controversial due to inconsistent results, serious side-effects, lack of convenience and high costs. The use of TOT in the management of burns needs further exploration by scientists and clinicians alike, in addition to the implementation of a standardised treatment protocol.
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Queimaduras , Ferida Cirúrgica , Animais , Suínos , Cicatrização , Matriz Extracelular , Retalhos CirúrgicosRESUMO
BACKGROUND: Although uncertainties exist regarding implementation, artificial intelligence-driven generative language models (GLMs) have enormous potential in medicine. Deployment of GLMs could improve patient comprehension of clinical texts and improve low health literacy. OBJECTIVE: The goal of this study is to evaluate the potential of ChatGPT-3.5 and GPT-4 to tailor the complexity of medical information to patient-specific input education level, which is crucial if it is to serve as a tool in addressing low health literacy. METHODS: Input templates related to 2 prevalent chronic diseases-type II diabetes and hypertension-were designed. Each clinical vignette was adjusted for hypothetical patient education levels to evaluate output personalization. To assess the success of a GLM (GPT-3.5 and GPT-4) in tailoring output writing, the readability of pre- and posttransformation outputs were quantified using the Flesch reading ease score (FKRE) and the Flesch-Kincaid grade level (FKGL). RESULTS: Responses (n=80) were generated using GPT-3.5 and GPT-4 across 2 clinical vignettes. For GPT-3.5, FKRE means were 57.75 (SD 4.75), 51.28 (SD 5.14), 32.28 (SD 4.52), and 28.31 (SD 5.22) for 6th grade, 8th grade, high school, and bachelor's, respectively; FKGL mean scores were 9.08 (SD 0.90), 10.27 (SD 1.06), 13.4 (SD 0.80), and 13.74 (SD 1.18). GPT-3.5 only aligned with the prespecified education levels at the bachelor's degree. Conversely, GPT-4's FKRE mean scores were 74.54 (SD 2.6), 71.25 (SD 4.96), 47.61 (SD 6.13), and 13.71 (SD 5.77), with FKGL mean scores of 6.3 (SD 0.73), 6.7 (SD 1.11), 11.09 (SD 1.26), and 17.03 (SD 1.11) for the same respective education levels. GPT-4 met the target readability for all groups except the 6th-grade FKRE average. Both GLMs produced outputs with statistically significant differences (P<.001; 8th grade P<.001; high school P<.001; bachelors P=.003; FKGL: 6th grade P=.001; 8th grade P<.001; high school P<.001; bachelors P<.001) between mean FKRE and FKGL across input education levels. CONCLUSIONS: GLMs can change the structure and readability of medical text outputs according to input-specified education. However, GLMs categorize input education designation into 3 broad tiers of output readability: easy (6th and 8th grade), medium (high school), and difficult (bachelor's degree). This is the first result to suggest that there are broader boundaries in the success of GLMs in output text simplification. Future research must establish how GLMs can reliably personalize medical texts to prespecified education levels to enable a broader impact on health care literacy.
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BACKGROUND: The transition to clinical clerkships can be difficult for medical students, as it requires the synthesis and application of preclinical information into diagnostic and therapeutic decisions. ChatGPT-a generative language model with many medical applications due to its creativity, memory, and accuracy-can help students in this transition. OBJECTIVE: This paper models ChatGPT 3.5's ability to perform interactive clinical simulations and shows this tool's benefit to medical education. METHODS: Simulation starting prompts were refined using ChatGPT 3.5 in Google Chrome. Starting prompts were selected based on assessment format, stepwise progression of simulation events and questions, free-response question type, responsiveness to user inputs, postscenario feedback, and medical accuracy of the feedback. The chosen scenarios were advanced cardiac life support and medical intensive care (for sepsis and pneumonia). RESULTS: Two starting prompts were chosen. Prompt 1 was developed through 3 test simulations and used successfully in 2 simulations. Prompt 2 was developed through 10 additional test simulations and used successfully in 1 simulation. CONCLUSIONS: ChatGPT is capable of creating simulations for early clinical education. These simulations let students practice novel parts of the clinical curriculum, such as forming independent diagnostic and therapeutic impressions over an entire patient encounter. Furthermore, the simulations can adapt to user inputs in a way that replicates real life more accurately than premade question bank clinical vignettes. Finally, ChatGPT can create potentially unlimited free simulations with specific feedback, which increases access for medical students with lower socioeconomic status and underresourced medical schools. However, no tool is perfect, and ChatGPT is no exception; there are concerns about simulation accuracy and replicability that need to be addressed to further optimize ChatGPT's performance as an educational resource.