Tissue Engineering Auricular Cartilage: A Review of Auricular Cartilage Characteristics and Current Techniques for Auricular Reconstruction.

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.

ChatGPT Interactive Medical Simulations for Early Clinical Education: Case Study.

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.

Combining Allograft Adipose and Fascia Matrix as an Off-the-Shelf Scaffold for Adipose Tissue Engineering Stimulates Angiogenic Responses and Activates a Proregenerative Macrophage Profile in a Rodent Model.

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.

Targeting Myofibroblasts as a Treatment Modality for Dupuytren Disease.

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.

Hyperbaric and topical oxygen therapies in thermal burn wound healing: a review

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.