Factors influencing surgical care and outcome of pediatric burn injuries and the use of synthetic skin substitutes.

Burn trauma is one of the most common causes of inpatient treatment in children and is associated with severe physical and psychological consequences. Synthetic skin substitutes are designed to reduce the risk of infection, minimize wound pain, and reduce the frequency of dressing changes. However, data regarding premature detachment of these materials is scarce. The aim of this study was to identify factors associated with early detachment and subsequent consequences for surgical treatment. A retrospective analysis of 392 children with superficial and deep partial thickness burns undergoing inpatient treatment with application of a skin substitute (Suprathel®) was performed. Patient age, wound localization and progression as well as burned total body surface area (TBSA %) were investigated as possible risk factors for early detachment of wound dressings and surgical intervention. Premature material detachement was significantly associated with burn localization (p < 0.001) and correlated with burn depth progression (r = 0.23, < 0.001) and patient age (r = 0.22, < 0.001). Surgical revision after material detachment were required in 13 % of patients. Patient age and burn localization seem to increase the risk of premature material detachement. In addition, we observed increased premature detachment of Suprathel®in areas which elicited higher wound progression rates. Identifying these areas might prove pivotal in the improvement of pediatric burn trauma management.

Antiseptic management of critical wounds: differential bacterial response upon exposure to antiseptics and first insights into antiseptic/phage interactions - experimental studies.

BACKGROUND: With the antibiotic crisis, the topical antibacterial control including chronic wounds gains increasing importance. However, little is known regarding tolerance development when bacteria face repetitive exposure to the identical antiseptics as commonly found in clinical practice. MATERIALS AND METHODS: We exposed clinical isolates foremost of chronic wounds in vitro to dilutions of two antisepctics used for wound therapy: polyhexanide or octenidine. Adaptive response was determined by growth/kill curves, minimal inhibitory concentration (MIC), and whole genome sequencing. Antiseptic/bacteriophage combinations were studied by liquid-infection assays and bacterial plating. RESULTS: Polyhexanide acted stronger against Escherichia coli and Proteus mirabilis while octenidine was more potent against Staphylococcus aureus. Otherwise, the antiseptic efficacy varied across isolates of Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Upon repetitive exposure with constant antiseptic concentrations P. aeruginosa and P. mirabilis adaptation was evident by a reduced lag-phase and a two-fold increased MIC. Under increasing octenidine concentrations, P. aeruginosa adapted to an eightfold higher dosage with mutations in smvA, opgH and kinB affecting an efflux pump, alginate and biofilm formation, respectively. S. aureus adapted to a fourfold increase of polyhexanide with a mutation in the multiple peptide resistance factor MprF, also conferring cross-resistance to daptomycin. Antiseptic/bacteriophage combinations enhanced bacterial inhibition and delayed adaptation. CONCLUSION: Different bacterial species/strains respond unequally to low-level antiseptic concentrations. Bacterial adaptation potential at phenotypic and genotypic levels may indicate the necessity for a more nuanced selection of antiseptics. Bacteriophages represent a promising yet underexplored strategy for supporting antiseptic treatment which may be particularly beneficial for the management of critical wounds.

Integrating AI in Lipedema Management: Assessing the Efficacy of GPT-4 as a Consultation Assistant.

The role of artificial intelligence (AI) in healthcare is evolving, offering promising avenues for enhancing clinical decision making and patient management. Limited knowledge about lipedema often leads to patients being frequently misdiagnosed with conditions like lymphedema or obesity rather than correctly identifying lipedema. Furthermore, patients with lipedema often present with intricate and extensive medical histories, resulting in significant time consumption during consultations. AI could, therefore, improve the management of these patients. This research investigates the utilization of OpenAI's Generative Pre-Trained Transformer 4 (GPT-4), a sophisticated large language model (LLM), as an assistant in consultations for lipedema patients. Six simulated scenarios were designed to mirror typical patient consultations commonly encountered in a lipedema clinic. GPT-4 was tasked with conducting patient interviews to gather medical histories, presenting its findings, making preliminary diagnoses, and recommending further diagnostic and therapeutic actions. Advanced prompt engineering techniques were employed to refine the efficacy, relevance, and accuracy of GPT-4's responses. A panel of experts in lipedema treatment, using a Likert Scale, evaluated GPT-4's responses across six key criteria. Scoring ranged from 1 (lowest) to 5 (highest), with GPT-4 achieving an average score of 4.24, indicating good reliability and applicability in a clinical setting. This study is one of the initial forays into applying large language models like GPT-4 in specific clinical scenarios, such as lipedema consultations. It demonstrates the potential of AI in supporting clinical practices and emphasizes the continuing importance of human expertise in the medical field, despite ongoing technological advancements.

HER3 (ERBB3) amplification in liposarcoma - a putative new therapeutic target?

BACKGROUND: Liposarcomas are among the most common mesenchymal malignancies. However, the therapeutic options are still very limited and so far, targeted therapies had not yet been established. Immunotherapy, which has been a breakthrough in other oncological entities, seems to have no efficacy in liposarcoma. Complicating matters further, classification remains difficult due to the diversity of morphologies and nonspecific or absent markers in immunohistochemistry, leaving molecular pathology using FISH or sequencing as best options. Many liposarcomas harbor MDM2 gene amplifications. In close relation to the gene locus of MDM2, HER3 (ERBB3) gene is present and co-amplification could occur. Since the group of HER/EGFR receptor tyrosine kinases and its inhibitors/antibodies play a role in a broad spectrum of oncological diseases and treatments, and some HER3 inhibitors/antibodies are already under clinical investigation, we hypothesized that in case of HER3 co-amplifications a tumor might bear a further potential therapeutic target. METHODS: We performed FISH analysis (MDM2, DDIT3, HER3) in 56 archived cases and subsequently performed reclassification to confirm the diagnosis of liposarcoma. RESULTS: Next to 16 out of 56 cases needed to be re-classified, in 20 out of 54 cases, a cluster-amplification of HER3 could be detected, significantly correlating with MDM2 amplification. Our study shows that the entity of liposarcomas show specific molecular characteristics leading to reclassify archived cases by modern, established methodologies. Additionally, in 57.1% of these cases, HER3 was cluster-amplified profusely, presenting a putative therapeutic target for targeted therapy. CONCLUSION: Our study serves as the initial basis for further investigation of the HER3 gene as a putative therapeutic target in liposarcoma.

[Nerve Transfers in Children with Non-traumatic Amyoplasia] / Nerventransfers bei Kindern mit nicht traumatischer AmyoplasieNerve Transfers in Children with Non-traumatic Amyoplasia.

BACKGROUND: The treatment of obstetric brachial plexus palsy through primary reconstruction and nerve transfers has been established in the past decades. In the case of non-traumatic diseases that lead to flaccid paralysis and the inability to move the extremities, such as transverse myelitis (TM) or arthrogryposis multiplex congenita (AMC), which can have a wide variety of causes, the focus has been on rehabilitative therapy so far, while surgical interventions have been used to a lesser extent, e. g., in the form of osteotomies or muscle transfers. Our aim is to establish nerve transfers as a surgical option to improve mobility in non-traumatic amyoplasia. PATIENTS: This work presents the needs-adapted treatment of a total of 23 patients (aged 4 months to 64 months, 18 with AMC and 5 with TM) using nerve transfers on the upper extremity. RESULTS: We were able to show that early nerve transfers in the upper extremity enabled the reanimation of muscles in both AMC and TM. CONCLUSION: This work shows that the treatment of non-traumatic amyoplasia in children with selective nerve grafts is a successful method. Nerve transfers allow patients to gain or regain important functions for managing independent everyday life. The surgical methods have been established in the treatment of traumatic nerve injuries. They are well-known and can be carried out safely. We believe that this is an important treatment option for paediatric patients with paralysis associated with TM or AMC, which should also be known to the treating physicians.

[Contralateral C7 Nerve Transfer]. / Der kontralaterale C7 Transfer.

Complex brachial plexus injuries with multiple or complete root avulsions make intraplexic reconstruction impossible in some cases. Such cases necessitate the use of extraplexic nerve donors such as the spinal accessory nerve or intercostal nerves. The contralateral C7 root represents a donor with a high axon count and can be used as an axon source in such cases. We summarise current indications, surgical technique and functional results after a contralateral C7 transfer in cases of brachial plexus injury, describing some of our own cases and including a selective literature review.

Association between Donor Age and Osteogenic Potential of Human Adipose Stem Cells in Bone Tissue Engineering.

Adipose stem cells (ASCs) have multilineage differentiation capacity and hold great potential for regenerative medicine. Compared to bone marrow-derived mesenchymal stem cells (bmMSCs), ASCs are easier to isolate from abundant sources with significantly higher yields. It is generally accepted that bmMSCs show age-related changes in their proliferation and differentiation potentials, whereas this aspect is still controversial in the case of ASCs. In this review, we evaluated the existing data on the effect of donor age on the osteogenic potential of human ASCs. Overall, a poor agreement has been achieved because of inconsistent findings in the previous studies. Finally, we attempted to delineate the possible reasons behind the lack of agreements reported in the literature. ASCs represent a heterogeneous cell population, and the osteogenic potential of ASCs can be influenced by donor-related factors such as age, but also gender, lifestyle, and the underlying health and metabolic state of donors. Furthermore, future studies should consider experimental factors in in vitro conditions, including passaging, cryopreservation, culture conditions, variations in differentiation protocols, and readout methods.

GPR55 inhibits the pro-adipogenic activity of anandamide in human adipose stromal cells.

The endocannabinoid anandamide (AEA) stimulates adipogenesis via the cannabinoid receptor CB1 in adipose stromal cells (ASCs). However, AEA interacts also with nonclassical cannabinoid receptors, including transient receptor potential cation channel (TRPV)1 and G protein-coupled receptor (GPR)55. Their roles in AEA mediated adipogenesis of human ASCs have not been investigated. We examined the receptor-expressions by immunostaining on human ASCs and tested their functionality by measuring the expression of immediate early genes (IEGs) related to the transcription factor-complex AP-1 upon exposition to receptor agonists. Cells were stimulated with increasing concentrations of specific ligands to investigate the effects on ASC viability (proliferation and metabolic activity), secretory activity, and AEA mediated differentiation. ASCs expressed both receptors, and their activation suppressed IEG expression. TRPV1 did not affect viability or cytokine secretion. GPR55 decreased proliferation, and it inhibited the release of hepatocyte growth factor. Blocking GPR55 increased the pro-adipogenic activity of AEA. These data suggest that GPR55 functions as negative regulator of cannabinoid mediated pro-adipogenic capacity in ASCs.

ITIH5 inhibits proliferation, adipogenic differentiation, and secretion of inflammatory cytokines of human adipose stem cells-A new key in treating obesity?

Inter-α-trypsin inhibitor heavy chain 5 (ITIH5) is widely expressed in the human body, and it is detected to be particularly abundant in adipose tissue. ITIH5 expression is increased in people with obesity compared to lean persons and is decreased by diet-induced weight loss. This suggests that ITIH5 may be involved in the development of adiposity and clinical metabolic variables, although its exact function remains unknown. We measured the protein concentration of ITIH5 in adipose samples from patients undergoing abdominoplasty and tested for correlation with the subjects' BMI as well as inflammatory mediators. We stimulated human adipose stem cells (ASCs) with recombinant (r)ITIH5 protein and tested for an effect on proliferation, differentiation, and immunosuppressive properties when the cells were exposed to an artificial inflammatory environment. We found positive correlations between ITIH5 levels and the BMI (p < .001) as well as concentrations of inflammatory cytokines (TNF-α, IL-6, and MCP-1) in adipose tissue (p < .01). Application of the rITIH5 protein inhibited both proliferation (p < .001) and differentiation of ASCs. Especially, the development of mature adipocytes was reduced by over 50%. Moreover, rITIH5 decreased the release of IL-6 and MCP-1 when the cells were exposed to TNF-α and IL-1ß (p < .001). Our data suggest that ITIH5 is an adipokine that is increasingly released during human adipose tissue development, acting as a regulator that inhibits proliferation and adipogenic differentiation of ASCs. ITIH5 thus presents itself as a positive regulator of adipose tissue homeostasis, possibly protecting against both hyperplasia and hypertrophy of adipose tissue and the associated chronic inflammation.

Can AI Think Like a Plastic Surgeon? Evaluating GPT-4's Clinical Judgment in Reconstructive Procedures of the Upper Extremity.

This study delves into the potential application of OpenAI's Generative Pretrained Transformer 4 (GPT-4) in plastic surgery, with a particular focus on procedures involving the hand and arm. GPT-4, a cutting-edge artificial intelligence (AI) model known for its advanced chat interface, was tested on nine surgical scenarios of varying complexity. To optimize the performance of GPT-4, prompt engineering techniques were used to guide the model's responses and improve the relevance and accuracy of its output. A panel of expert plastic surgeons evaluated the responses using a Likert scale to assess the model's performance, based on five distinct criteria. Each criterion was scored on a scale of 1 to 5, with 5 representing the highest possible score. GPT-4 demonstrated a high level of performance, achieving an average score of 4.34 across all cases, consistent across different complexities. The study highlights the ability of GPT-4 to understand and respond to complicated surgical scenarios. However, the study also identifies potential areas for improvement. These include refining the prompts used to elicit responses from the model and providing targeted training with specialized, up-to-date sources. This study demonstrates a new approach to exploring large language models and highlights potential future applications of AI. These could improve patient care, refine surgical outcomes, and even change the way we approach complex clinical scenarios in plastic surgery. However, the intrinsic limitations of AI in its current state, together with the potential ethical considerations and the inherent uncertainty of unanticipated issues, serve to reiterate the indispensable role and unparalleled value of human plastic surgeons.

Effects of epinephrine, lidocaine, and prilocaine on viability and differentiation capacity of human adipose stem cells.

INTRODUCTION: Local anesthetics (LAs) are routinely administered in plastic and reconstructive surgery, e.g., as tumescent anesthesia adjunct in liposuction. Historically, these substances were assumed to act cytotoxically. Thus, the application of LA was avoided when handling adipose stem cells (ASCs). We recently determined that most LAs are not cytotoxic when ASCs are exposed to concentrations used for tumescent liposuction. However, there is limited information when combining LA with epinephrine and about the effects of prilocaine on ASCs. METHODS: We analyzed the effects of prilocaine or lidocaine in co-exposure with epinephrine on the viability of primary human ASCs, i.e., proliferation, metabolic activity, and cytotoxicity, using crystal violet-staining, PrestoBlue®-, and WST-1 assay. We quantified the impact of short-term incubation of lidocaine and epinephrine on the differentiation of ASCs into the adipogenic, chondrogenic, and osteogenic lineage. RESULTS: After 2 h, prilocaine (10 mM) significantly reduced metabolic activity and cell numbers, whereas lidocaine only inhibited metabolic activity. After 6 h, prilocaine (10 mM) and lidocaine significantly decreased metabolic activity as well as cell numbers. The application of high concentrations of epinephrine did not affect cell numbers but diminished metabolic activity. Combining lidocaine with epinephrine had no additional cytotoxic effect. Differentiation into the chondrogenic lineage was significantly inhibited by epinephrine. CONCLUSIONS: Deducing from our data, neither lidocaine combined with epinephrine nor prilocaine has a cytotoxic impact on ASCs in vitro at concentrations equivalent to those in tumescent anesthesia and has no long-lasting effect on the differentiation capacity of ASCs into the osteogenic and adipogenic lineage.

Hyperbaric oxygen treatment in carbon monoxide poisoning - Does it really matter?

Carbon monoxide (CO) is an odorless and colorless gas that can lead to fulminant and life-threatening intoxications. Besides an early diagnosis, an appropriate treatment of the intoxication is important. In this context the reduction of CO concentration in blood and tissues is crucial revealing hyperbaric oxygen treatment (HBO) as a highly promising tool. However, the benefit of HBO in CO intoxications is still considered controversial. In this review, we discuss the evidence of the role of HBO treatment in isolated CO intoxication.

Three-Dimensional Bioprinting in Soft Tissue Engineering for Plastic and Reconstructive Surgery.

Skeletal muscle tissue engineering (TE) and adipose tissue engineering have undergone significant progress in recent years. This review focuses on the key findings in these areas, particularly highlighting the integration of 3D bioprinting techniques to overcome challenges and enhance tissue regeneration. In skeletal muscle TE, 3D bioprinting enables the precise replication of muscle architecture. This addresses the need for the parallel alignment of cells and proper innervation. Satellite cells (SCs) and mesenchymal stem cells (MSCs) have been utilized, along with co-cultivation strategies for vascularization and innervation. Therefore, various printing methods and materials, including decellularized extracellular matrix (dECM), have been explored. Similarly, in adipose tissue engineering, 3D bioprinting has been employed to overcome the challenge of vascularization; addressing this challenge is vital for graft survival. Decellularized adipose tissue and biomimetic scaffolds have been used as biological inks, along with adipose-derived stem cells (ADSCs), to enhance graft survival. The integration of dECM and alginate bioinks has demonstrated improved adipocyte maturation and differentiation. These findings highlight the potential of 3D bioprinting techniques in skeletal muscle and adipose tissue engineering. By integrating specific cell types, biomaterials, and printing methods, significant progress has been made in tissue regeneration. However, challenges such as fabricating larger constructs, translating findings to human models, and obtaining regulatory approvals for cellular therapies remain to be addressed. Nonetheless, these advancements underscore the transformative impact of 3D bioprinting in tissue engineering research and its potential for future clinical applications.

First Series of Free Flap Reconstruction Using a Dedicated Robotic System in a Multidisciplinary Microsurgical Center.

Robotic microsurgery is a novel technology for microsurgical free flap transplantation in reconstructive surgery. Recently, the first free flap transplantation using a dedicated robotic system for microsurgery (Symani Surgical System; Medical Microinstruments) was published for a single reconstructive case. For broader future application, evaluating its potential benefits in different anatomical regions, anastomotic configurations, and clinical scenarios is necessary. In this world-wide first free flap series using this robotic system, we describe our experience with this new technology in a multidisciplinary microsurgical center. The robotic system was used for different free flaps in a range of reconstructive applications in plastic surgery, oral and maxillofacial surgery, and head and neck surgery. A total of 23 flaps were performed, with all 23 arterial and a selection of two venous anastomoses being performed with the robotic system. Time for anastomoses was significantly longer than commonly. Five of the arterial robotic anastomoses had to be redone. All but one flap survived. We could show that this new dedicated microsurgical robotic system is feasible for carrying out robot-assisted anastomoses in end-to-end, as well as end-to-side fashion under varying clinical conditions and in different microsurgical subspecialties. However, some drawbacks still need to be overcome, which are partly related to individual and institutional learning curves, to finally estimate the potential benefit for robotic free flap surgery. Multidisciplinary application of the robotic system may accelerate this process by putting together different microsurgical backgrounds, while economic burden of establishing this new technology is spread among several departments.

Nerve Transfers Using a Dedicated Microsurgical Robotic System.

Microsurgical demands in peripheral nerve surgery are increasing. Because of the development of multiple simultaneous selective nerve transfers, the transposition of very small nerves and even single fascicles has evolved. Coaptation of these increasingly smaller structures require high skills in microsurgical techniques. In addition, the surgical situs often has very limited access and is difficult to reach with conventional microsurgical options. Robot technology, the Symani Surgical System (Medical Microinstruments, S.p.A, Calci, Pisa, Italy), was used for epineural coaptation of three donor nerves (intercostal nerves 4-6) to the long thoracic nerve and the thoracodorsal nerve as recipient nerves in a patient with brachial plexus palsy. The coaptations could be carried out successfully with the microsurgical robot technology. In combination with a high-magnification (up to 26×) 3D-exoscope, the epineural sutures could be placed very precisely and accurately. Using this new microsurgical robotic system, successful coaptation of very small nerve structures is possible. This opens possibilities for the microsurgeon to carry out even finer, more targeted and more complex nerve transfers, including procedures in anatomical regions that are difficult to reach.

Prospective analysis of grip strength and load distribution after surgical treatment of common diseases of the hand with novel's manugraphy® system.

BACKGROUND: Carpal tunnel syndrome, A1 annular pulley stenosis and Dupuytren's contracture are among the most common conditions of the hand. In this study, we investigated the impact of surgical procedure on hand grip strength and high-resolution spatial load distribution in individuals suffering from those diseases over a follow-up period of one year. MATERIALS AND METHODS: In this prospective study, data of 9 patients with carpal tunnel syndrome, 12 patients with A1 annular pulley stenosis and 7 patients with Dupuytren's contracture were evaluated. Only patients with unilateral disease were included providing the contralateral hand as an intra-individual control. Grip strength was measured with cylindrical instruments in two different sizes with respect to the hand size of the patients. Maximum and average values of grip strength as well as spatial load distribution in each finger, thenar, hypothenar and palm were analyzed. Data of the affected patients were collected preoperatively and 6 weeks, 6 months and 1 year postoperatively. Grip strength and spatial load distribution were compared preoperatively to postoperatively. In addition, DASH score, Levine score, 2-point discrimination and degree of flexion contracture were assessed. RESULTS: The patients with A1 annular pulley stenosis showed a significant increase in grip strength 6 months and one year postoperatively. Patients with carpal tunnel syndrome and Dupuytren's contracture showed no significant difference in grip strength over the course of time. An increase in the percentual grip strength of the thenar in patients with carpal tunnel disease and within the affected finger in A1 annular pulley stenosis was observed over the course of time. The DASH score was significantly lower in all patient cohorts one year postoperatively. CONCLUSION: Surgical procedure in carpal tunnel syndrome, A1 annular ligament stenosis and Dupuytren's contracture improves the functionality of the hand in everyday life. Some areas of the hand seem to compensate other weaker areas in grip strength.

Reconstructive and Aesthetic Surgeries on the Female Genitalia. Guideline of the DGGG, DGPRÄC, OEGGG and SGGG (S2k-Level, AWMF Registry No. 009/019, May 2022).

Aim This official guideline was coordinated and published by the German Society for Gynaecology and Obstetrics (DGGG), the German Society for Plastic, Reconstructive and Aesthetic Surgery (DGPRÄC), the Austrian Society for Gynaecology and Obstetrics (OEGGG), and the Swiss Society for Gynaecology and Obstetrics (SGGG). The guideline aims to provide a consensus-based overview of reconstructive and aesthetic surgeries on female genitalia based on an evaluation of the relevant literature. Methods This S2k-guideline was developed by representative members from different medical professions on behalf of the guidelines commission of the DGGG, DGPRÄC, OEGGG and SGGG using a structured consensus process. Recommendations Statements and recommendations on the epidemiology, aetiology, classification, symptoms, diagnosis, and treatment of acquired changes of the external genitalia are presented and special situations are discussed.

Myogenic differentiation of human myoblasts and Mesenchymal stromal cells under GDF11 on NPoly-ɛ-caprolactone-collagen I-Polyethylene-nanofibers.

BACKGROUND: For the purpose of skeletal muscle engineering, primary myoblasts (Mb) and adipogenic mesenchymal stem cells (ADSC) can be co-cultured and myogenically differentiated. Electrospun composite nanofiber scaffolds represent suitable matrices for tissue engineering of skeletal muscle, combining both biocompatibility and stability Although growth differentiation factor 11 (GDF11) has been proposed as a rejuvenating circulating factor, restoring skeletal muscle function in aging mice, some studies have also described a harming effect of GDF11. Therefore, the aim of the study was to analyze the effect of GDF11 on co-cultures of Mb and ADSC on poly-ε-caprolactone (PCL)-collagen I-polyethylene oxide (PEO)-nanofibers. RESULTS: Human Mb were co-cultured with ADSC two-dimensionally (2D) as monolayers or three-dimensionally (3D) on aligned PCL-collagen I-PEO-nanofibers. Differentiation media were either serum-free with or without GDF11, or serum containing as in a conventional differentiation medium. Cell viability was higher after conventional myogenic differentiation compared to serum-free and serum-free + GDF11 differentiation as was creatine kinase activity. Immunofluorescence staining showed myosine heavy chain expression in all groups after 28 days of differentiation without any clear evidence of more or less pronounced expression in either group. Gene expression of myosine heavy chain (MYH2) increased after serum-free + GDF11 stimulation compared to serum-free stimulation alone. CONCLUSIONS: This is the first study analyzing the effect of GDF11 on myogenic differentiation of Mb and ADSC co-cultures under serum-free conditions. The results of this study show that PCL-collagen I-PEO-nanofibers represent a suitable matrix for 3D myogenic differentiation of Mb and ADSC. In this context, GDF11 seems to promote myogenic differentiation of Mb and ADSC co-cultures compared to serum-free differentiation without any evidence of a harming effect.

Comprehensive Analysis of Local Anesthetics Affecting Adipose Stem Cells In Vitro.

BACKGROUND: Adipose stem cells (ASCs) hold a great regenerative capacity because of their differentiation capability and their secretory activity. Thus, ASC survival is of great significance during perioperative harvesting. Various local anesthetics are commonly applied during fat grafting procedures. These substances are known to impair cellular viability, which would affect graft survival and final outcomes, but the exact extent of their impact on ASC biology is unknown. METHODS: The authors analyzed the short- and long-term effects of lidocaine, mepivacaine, ropivacaine, and bupivacaine at increasing concentrations (0.1 to 10 mM) on primary human ASC proliferation and metabolic activity. Trilinear differentiation was assessed by oil red O stain (adipogenesis), safranin O (chondrogenesis), and cresolphthalein (osteogenesis) labeling. In supernatants, cytokine [interleukin (IL)-6/IL-8, vascular endothelial growth factor, hepatocyte growth factor] secretion was analyzed by enzyme-linked immunosorbent assay. RESULTS: Bupivacaine at greater than 100 µM demonstrated the strongest anti proliferative effects, whereas lidocaine and ropivacaine did not affect cell numbers. Mepivacaine evoked reciprocal results regarding cell count at greater than 1 mM. Each compound impaired trilinear differentiation. Secretion of hepatocyte growth factor and IL-8 was reduced significantly by local anesthetic exposure; levels were restored after substances were washed out. CONCLUSIONS: In vitro data show that lidocaine, mepivacaine, and ropivacaine could be applied at concentrations of 1 to 10 mM without affecting ASC survival. In contrast, bupivacaine at concentrations greater than 100 µM should be administered with great caution. The differentiation of ASCs and the ASC's secretome might already be decreased by each local anesthetic at 1 mM. CLINICAL RELEVANCE STATEMENT: The authors' experimental data can be of great significance to the clinical practice, as local anesthetics are routinely administered during liposuction as a tumescent anesthesia adjunct. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.