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1.
Clin Exp Med ; 24(1): 82, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38653874

ABSTRACT

PURPOSE: Vascularized lymph node transfer (VLNT) entails the autologous relocation of lymph nodes to a lymphedematous region of the body, whereas lymphaticovenous anastomosis (LVA) creates a direct bypass between the lymphatic and venous system. Both techniques are meant to lastingly bolster the local lymphatic drainage capacity. This study compared safety and effectiveness of VLNT and LVA in patients with chronic breast cancer related lymphedema (BCRL). METHODS: A retrospective cohort study was conducted using data from our encrypted database composed of patients with chronic BCRL who were treated with either VLNT or LVA and had a minimum follow-up of two years. Patient-specific variables analyzed included pre- and postoperative arm circumferences, lymphedema stages and postoperative complications. RESULTS: A total of 105 patients met the inclusion criteria, of which 96 patients demonstrated a complete follow-up period of two years. The VLNT group displayed larger preoperative circumferential measurements, evident in both in the isolated examination of the affected arm, as well as when adjusted for the contralateral unaffected arm. Significant reduction in arm volume was achieved by both groups. However, VLNT demonstrated superior relative reduction rates than LVA, neutralizing any significant arm size disparities after 24 months. Surgery duration was slightly longer for VLNT than LVA. Postoperative complications, predominantly minor, were exclusively observed in the VLNT group. CONCLUSIONS: Both VLNT and LVA offer significant improvement for patients suffering from chronic BCRL. VLNT shows an even greater potential for improvement in more severe cases of BCRL, but involves a higher risk for (mostly minor) complications.


Subject(s)
Breast Cancer Lymphedema , Microsurgery , Quality of Life , Humans , Female , Middle Aged , Retrospective Studies , Breast Cancer Lymphedema/surgery , Microsurgery/methods , Aged , Adult , Anastomosis, Surgical , Lymph Nodes/pathology , Lymph Nodes/surgery , Treatment Outcome , Breast Neoplasms/surgery , Breast Neoplasms/complications , Postoperative Complications , Lymphedema/surgery , Lymphedema/etiology
2.
Cancer Immunol Res ; 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38631025

ABSTRACT

Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is effective in melanoma patients, although long-term responses seem restricted to patients who have complete remissions. Many patients develop secondary resistance to TIL-ACT but the involved mechanisms are unclear. Here, we describe a case of secondary resistance to TIL-ACT likely due to intratumoral heterogeneity and selection of a resistant tumor cell clone by the transferred T cells. To our knowledge, this is the first case of clonal selection of a pre-existing non-dominant tumor cell clone and it demonstrates a mechanism involved in secondary resistance to TIL-ACT that could potentially change current clinical practice, because it advocates for T-cell collection from multiple tumor sites and analysis of tumor heterogeneity before the treatment with TIL-ACT.

3.
Plast Reconstr Surg Glob Open ; 12(4): e5708, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38596574

ABSTRACT

Background: Recalcitrant bone nonunion and osseous defect treatment is challenging and often requires vascularized bone transfer. The medial femoral condyle flap has become an increasingly popular option for reconstruction. The study aims at reviewing its different applications and synthesizing its surgical outcomes. Method: A systematic review including all studies assessing surgical outcomes of free medial femoral condyle flap for bone reconstruction in adults was conducted on January 31, 2023. Flap failure and postoperative complications were synthesized with a proportional meta-analysis. Results: Forty articles describing bony reconstruction in the head and neck, upper limb, and lower limb areas were selected. Indications ranged from bony nonunion and bone defects to avascular bone necrosis. Multiple flaps were raised as either pure periosteal, cortico-periosteal, cortico-cancellous-periosteal, or cortico-chondro-periosteal. A minority of composite flaps were reported. Overall failure rate was 1% [95% confidence interval (CI), 0.00-0.08] in head & neck applications, 4% in the lower limb (95% CI, 0.00-0.16), 2% in the upper limb (95% CI, 0.00-0.06), and 1% in articles analyzing various locations simultaneously (95% CI, 0.00-0.04). Overall donor site complication rate was 4% (95% CI, 0.01-0.06). Major reported complications were: femoral fractures (n = 3), superficial femoral artery injury (n = 1), medial collateral ligament injury (n = 1), and septic shock due to pace-maker colonization (n = 1). Conclusion: The medial femoral condyle flap is a versatile option for bone reconstruction with high success rates and low donor site morbidity.

4.
J Plast Reconstr Aesthet Surg ; 91: 24-34, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38401274

ABSTRACT

BACKGROUND: Limited data exist regarding the effect of adjuvant radiochemotherapy on free flap volume in head and neck reconstruction. However, an adequate free flap volume is an important predictor of functional and patient-reported outcomes in head and neck reconstruction. METHODS: A systematic review of Medline, Embase, and the Cochrane Central Register of Controlled Trials was conducted using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. A total of 6710 abstracts were screened, and 36 full-text papers were reviewed. Nineteen studies met the inclusion criteria and were used to extract data for this analysis. RESULTS: A meta-analysis of 14 two-arm studies comparing the impact of adjuvant radiotherapy versus no adjuvant radiotherapy was performed. The main analysis revealed that 6 months postoperatively, irradiated flaps showed a significant reduction of volume (average, 9.4%) compared to nonirradiated flaps. The average interpolated pooled flap volumes 6 months postoperatively were 76.4% in irradiated flaps and 81.8% in nonirradiated flaps. After a median postoperative follow-up of 12 months, the total flap volume was 62.6% for irradiated flaps and 76% for nonirradiated flaps. Four studies reported that chemotherapy had no significant impact on free flap volume. CONCLUSIONS: Compared to nonirradiated flaps, irradiated flaps were significantly reduced in volume (range, 5% to 15.5%). Clinicians should take this into account when planning the surgical reconstruction of head and neck defects. Conducting large-scale prospective studies with standardized protocols and well-defined follow-up measurements could contribute to defining the ideal, personalized free flap volume for optimal function and patient-reported outcomes.


Subject(s)
Free Tissue Flaps , Head and Neck Neoplasms , Plastic Surgery Procedures , Humans , Chemoradiotherapy, Adjuvant , Prospective Studies , Head and Neck Neoplasms/surgery , Retrospective Studies
5.
Spinal Cord ; 62(1): 34-41, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38123748

ABSTRACT

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To identify risk factors associated with major complications after flap surgery in people with spinal cord injury or disorder (SCI/D) and stage III and IV pressure injury (PI). SETTING: Swiss hospital specialized in the treatment of people with SCI/D using the Basel Decubitus Approach. METHODS: We examined 60 risk factors for major postoperative complications in PIs over sacrum/coccyx, ischium or trochanter between 01/2016 and 12/2021. We performed descriptive analysis and computed global p-values using likelihood ratio tests adjusted for clustering of PIs in individuals. RESULTS: We included 220 PI treatment procedure from 149 individuals. The study population consisted of 163 (74%) men, 133 (60%) traumatic SCI, 136 (58%) stage IV PI, 198 (90%) individuals with paraplegia, 93 (42%) with osteomyelitis, and 85 (39%) with recurrent PI. Major complications 42 (19%) occurred more often in individuals with stage IV PI (p < 0.01), individuals without osteomyelitis (p < 0.03), and individuals with pathological blood concentrations of cystatin c (p < 0.028), calcium (p < 0.048), and vitamin B12 (p < 0.0049) as well as normal blood concentrations of HbA1c (p < 0.033). Immobilization (p < 0.0089) and hospital stay (p < 0.0001) of individuals with major complications was longer. CONCLUSION: In the Basel Decubitus Approach, stage IV PI, absence of osteomyelitis, reduced vitamin B12 and calcium, elevated cystatin c, and normal HbA1c should be addressed to reduce major complications.


Subject(s)
Osteomyelitis , Pressure Ulcer , Spinal Cord Injuries , Male , Humans , Female , Spinal Cord Injuries/complications , Spinal Cord Injuries/epidemiology , Spinal Cord Injuries/surgery , Retrospective Studies , Pressure Ulcer/etiology , Pressure Ulcer/complications , Calcium , Cystatin C , Glycated Hemoglobin , Risk Factors , Osteomyelitis/complications , Vitamin B 12
6.
Biomaterials ; 303: 122387, 2023 12.
Article in English | MEDLINE | ID: mdl-37977007

ABSTRACT

Endochondral ossification (ECO), the major ossification process during embryogenesis and bone repair, involves the formation of a cartilaginous template remodelled into a functional bone organ. Adipose-derived stromal cells (ASC), non-skeletal multipotent progenitors from the stromal vascular fraction (SVF) of human adipose tissue, were shown to recapitulate ECO and generate bone organs in vivo when primed into a hypertrophic cartilage tissue (HCT) in vitro. However, the reproducibility of ECO was limited and the major triggers remain unknown. We studied the effect of the expansion of cells and maturation of HCT on the induction of the ECO process. SVF cells or expanded ASC were seeded onto collagen sponges, cultured in chondrogenic medium for 3-6 weeks and implanted ectopically in nude mice to evaluate their bone-forming capacities. SVF cells from all tested donors formed mature HCT in 3 weeks whereas ASC needed 4-5 weeks. A longer induction increased the degree of maturation of the HCT, with a gradually denser cartilaginous matrix and increased mineralization. This degree of maturation was highly predictive of their bone-forming capacity in vivo, with ECO achieved only for an intermediate maturation degree. In parallel, expanding ASC also resulted in an enrichment of the stromal fraction characterized by a rapid change of their proteomic profile from a quiescent to a proliferative state. Inducing quiescence rescued their chondrogenic potential. Our findings emphasize the role of monolayer expansion and chondrogenic maturation degree of ASC on ECO and provides a simple, yet reproducible and effective approach for bone formation to be tested in specific clinical models.


Subject(s)
Chondrogenesis , Osteogenesis , Mice , Animals , Humans , Mice, Nude , Proteomics , Reproducibility of Results , Stromal Cells , Cell Differentiation , Cells, Cultured
7.
BMC Infect Dis ; 23(1): 730, 2023 Oct 26.
Article in English | MEDLINE | ID: mdl-37884860

ABSTRACT

BACKGROUND: The BioFire® FilmArray® Blood Culture Identification Panel 1 (BF-FA-BCIP) detects microorganisms with high accuracy in positive blood cultures (BC) - a key step in the management of patients with suspected bacteraemia. We aimed to compare the time to optimal antimicrobial therapy (OAT) for the BF-FA-BCIP vs. standard culture-based identification. METHODS: In this retrospective single-centre study with a before-after design, 386 positive BC cases with identification by BF-FA-BCIP were compared to 414 controls with culture-based identification. The primary endpoint was the time from BC sampling to OAT. Secondary endpoints were time to effective therapy, length of stay, (re-)admission to ICU, in-hospital and 30-day mortality. Outcomes were assessed using Cox proportional hazard models and logistic regressions. RESULTS: Baseline characteristics of included adult inpatients were comparable. Main sources of bacteraemia were urinary tract and intra-abdominal infection (19.2% vs. 22.0% and 16.8% vs. 15.7%, for cases and controls, respectively). Median (95%CI) time to OAT was 25.5 (21.0-31.2) hours with BF-FA-BCIP compared to 45.7 (37.7-51.4) hours with culture-based identification. We observed no significant difference for secondary outcomes. CONCLUSIONS: Rapid microorganism identification by BF-FA-BCIP was associated with a median 20-h earlier initiation of OAT in patients with positive BC. No impact on length of stay and mortality was noted. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04156633, registered on November 5, 2019.


Subject(s)
Anti-Infective Agents , Bacteremia , Adult , Humans , Anti-Bacterial Agents/therapeutic use , Bacteremia/diagnosis , Bacteremia/drug therapy , Blood Culture , Controlled Before-After Studies , Polymerase Chain Reaction , Retrospective Studies
8.
J Clin Med ; 12(15)2023 Jul 28.
Article in English | MEDLINE | ID: mdl-37568383

ABSTRACT

Congenital pseudarthrosis of forearm fractures is rare and is strongly associated with neurofibromatosis type 1 (NF1). Our case report illustrates the progression of a non-union of the ulna after minor trauma in a twelve-year-old boy, newly diagnosed with NF1, and presents the technique of microsurgical bone reconstruction, including the growth plate. More than seven years after the first operation, follow-up presents a favorable outcome with a pain-free patient and unrestricted function of the forearm after a secondary correction of the remaining radial bowing. This treatment is discussed with a comprehensive review of the current literature on ulnar congenital pseudarthrosis in PubMed and Google Scholar and free fibular growth plate transfer in PubMed and Google Scholar. Nine publications reporting on 20 cases of congenital ulnar non-unions were identified. With this reconstructive option, favorable outcomes were achieved in all cases with the union after primary surgery and complications requiring further surgeries in nine cases. The benefit of vascularized growth plate bone transfer in congenital ulna non-union seems to be significant compared to other therapies such as open reduction internal fixation (ORIF), non-vascularized bone grafts, or one-bone-forearms and beneficial when growth reconstruction is needed. Other techniques might be necessary to improve insufficient long-term results.

9.
Int J Mol Sci ; 24(9)2023 Apr 25.
Article in English | MEDLINE | ID: mdl-37175506

ABSTRACT

Cell-therapy-based nerve repair strategies hold great promise. In the field, there is an extensive amount of evidence for better regenerative outcomes when using tissue-engineered nerve grafts for bridging severe gap injuries. Although a massive number of studies have been performed using rodents, only a limited number involving nerve injury models of large animals were reported. Nerve injury models mirroring the human nerve size and injury complexity are crucial to direct the further clinical development of advanced therapeutic interventions. Thus, there is a great need for the advancement of research using large animals, which will closely reflect human nerve repair outcomes. Within this context, this review highlights various stem cell-based nerve repair strategies involving large animal models such as pigs, rabbits, dogs, and monkeys, with an emphasis on the limitations and strengths of therapeutic strategy and outcome measurements. Finally, future directions in the field of nerve repair are discussed. Thus, the present review provides valuable knowledge, as well as the current state of information and insights into nerve repair strategies using cell therapies in large animals.


Subject(s)
Mesenchymal Stem Cells , Peripheral Nerve Injuries , Peripheral Nervous System Diseases , Trauma, Nervous System , Humans , Animals , Rabbits , Dogs , Swine , Tissue Engineering , Schwann Cells/physiology , Stem Cells , Nerve Regeneration/physiology , Peripheral Nerve Injuries/therapy , Sciatic Nerve/injuries
10.
J Pers Med ; 13(4)2023 Mar 31.
Article in English | MEDLINE | ID: mdl-37108996

ABSTRACT

Thread carpal tunnel release (TCTR) has been reported to be safe and effective for the treatment of carpal tunnel syndrome. The aim of this study is to evaluate the modified TCTR for safety, efficacy, and postoperative recovery. Seventy-six extremities in 67 patients undergoing TCTR were analyzed pre- and postoperatively using clinical parameters and patient-reported outcome measures. Twenty-nine men and 38 women with a mean age of 59.9 ± 18.9 years underwent TCTR. The mean postoperative time to resume activities of daily living was 5.5 ± 5.5 days, analgesia was completed after 3.7 ± 4.6 days, and return to work was achieved after a mean of 32.6 ± 15.6 days for blue-collar workers and 4.6 ± 4.3 days for white-collar workers. The Boston Carpal Tunnel Questionnaire (BCTQ) and Disability of Arm, Shoulder, and Hand (DASH) scores were comparable with previous studies. Overall, two persistent compressions and one recurrence required open reoperation (3.9%). All three had been operated in the initial phase, and none required reoperation after an additional safety step was introduced. No other complications occurred. TCTR surgery appears to be a safe and reliable technique with almost no wound and scarring and a potentially faster recovery time than open techniques. Although our technical modifications may reduce the risk of incomplete release, TCTR requires both ultrasound and surgical skills and has a considerable learning curve.

11.
NPJ Regen Med ; 8(1): 15, 2023 Mar 13.
Article in English | MEDLINE | ID: mdl-36914692

ABSTRACT

Vascular endothelial growth factor-A (VEGF) physiologically regulates both angiogenesis and osteogenesis, but its application in bone tissue engineering led to contradictory outcomes. A poorly understood aspect is how VEGF dose impacts the coordination between these two processes. Taking advantage of a unique and highly tunable platform, here we dissected the effects of VEGF dose over a 1,000-fold range in the context of tissue-engineered osteogenic grafts. We found that osteo-angiogenic coupling is exquisitely dependent on VEGF dose and that only a tightly defined dose range could stimulate both vascular invasion and osteogenic commitment of progenitors, with significant improvement in bone formation. Further, VEGF dose regulated Notch1 activation and the induction of a specific pro-osteogenic endothelial phenotype, independently of the promotion of vascular invasion. Therefore, in a therapeutic perspective, fine-tuning of VEGF dose in the signaling microenvironment is key to ensure physiological coupling of accelerated vascular invasion and improved bone formation.

12.
Breast Cancer Res Treat ; 197(1): 83-92, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36287309

ABSTRACT

PURPOSE: We investigated whether a one-stage combination of vascularized lymph node transfer (VLNT) with water jet-assisted liposuction (WAL) can be safely performed and results in improved patient outcomes such as a greater reduction in arm volume when treating chronic breast cancer-related lymphedema (BCRL). METHODS: In this retrospective cohort study, we included all patients from our encrypted lymphedema database treated for chronic BCRL with VLNT or VLNT + WAL who had a minimum follow-up of two years. We analyzed patient-specific variables including arm circumferences as well as patient-reported outcomes before and after surgery as well as surgery time, surgery-related complications and patient satisfaction. RESULTS: Only the mean preoperative differences of the circumferences between the lymphedematous and the unaffected arm in individual patients showed a statistically significant difference between treatment groups (p < 0.05). Indeed, patients treated with VLNT + WAL had consistently larger differences in individual sets of arms and therefore more pronounced chronic BCRL. The mean surgery time was significantly longer in the VLNT + WAL group (p < 0.05). Complications were seldom and similar in both groups. Using a numeric rating scale, the level of patient satisfaction following treatment did not differ significantly between groups (p = 0.323). CONCLUSIONS: Our findings suggest that a one-stage combination of VLNT with WAL does not result in more complications even though it also entails a longer surgery time. This is acceptable as secondary interventions resulting in overall longer surgery times and higher costs can be avoided. A one-stage combination might be especially favourable for patients suffering from more severe chronic BCRL.


Subject(s)
Breast Cancer Lymphedema , Breast Neoplasms , Lymphedema , Humans , Female , Retrospective Studies , Breast Neoplasms/complications , Breast Neoplasms/surgery , Breast Cancer Lymphedema/etiology , Breast Cancer Lymphedema/surgery , Lymphedema/etiology , Lymphedema/surgery , Arm , Lymph Nodes
13.
J Spinal Cord Med ; 46(5): 705-715, 2023 09.
Article in English | MEDLINE | ID: mdl-36129337

ABSTRACT

CONTEXT: The treatment of pressure injury (PI) stage III and IV in people with spinal cord injury or spinal cord disorder (SCI/D) requires a multidisciplinary and surgical involvement. OBJECTIVES: This scoping review aims to identify published relevant surgical multidisciplinary treatment approaches, describe the elements and evaluate the effectiveness of the approaches. METHODS: We searched PubMed and Medline databases for studies about treatment approaches for people aged ≥18 years with chronic SCI/D and PI stage III or IV over ischium, trochanter or sacrum published between January 1990 and December 2021 in English or German language. Two independent reviewers screened the articles. One reviewer extracted information on study author(s), year of publication, study title, study design, country of origin, sample size as well as data on elements and effectiveness of the approaches. RESULTS: 10 different approaches were described in two retrospective cohort studies, three case series, five discussion papers, one review and one guideline. All approaches included debridement, flap surgery, pressure relief and immobilization as well as infection control. Some approaches described elements such as risk screening (7/10), osteomyelitis treatment (8/10), nutritional therapy (8/10), physiotherapy, occupational therapy and psychology (6/10), spasticity control (7/10), and prevention and education (6/10). Only one study reported on the effectiveness of the approaches. CONCLUSION: There are key elements for surgical multidisciplinary treatment approaches. However, due to differences in the content of some of these elements and missing elements in some approaches, comparability is difficult and the effectiveness of the complex approaches remains uncertain.


Subject(s)
Occupational Therapy , Pressure Ulcer , Spinal Cord Injuries , Humans , Adolescent , Adult , Spinal Cord Injuries/complications , Spinal Cord Injuries/therapy , Pressure Ulcer/therapy , Pressure Ulcer/prevention & control , Retrospective Studies
14.
J Invest Dermatol ; 143(2): 273-283.e12, 2023 02.
Article in English | MEDLINE | ID: mdl-36116506

ABSTRACT

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurring suppurating lesions of the intertriginous areas, resulting in a substantial impact on patients' QOL. HS pathogenesis remains poorly understood. An autoimmune component has been proposed, but disease-specific autoantibodies, autoantigens, or autoreactive T cells have yet to be described. In this study, we identify a high prevalence of IgM, IgG, and IgA antibodies directed against Nε-carboxyethyl lysine (CEL), a methylglyoxal-induced advanced glycation end-product, in the sera of patients with HS. Titers of anti-CEL IgG and IgA antibodies were highly elevated in HS compared with those in healthy controls and individuals with other inflammatory skin diseases. Strikingly, the majority of anti-CEL IgG was of the IgG2 subclass and correlated independently with both disease severity and duration. Both CEL and anti-CEL‒producing plasmablasts could be isolated directly from HS skin lesions, further confirming the disease relevance of this autoimmune response. Our data point to an aberration of the methylglyoxal pathway in HS and support an autoimmune axis in the pathogenesis of this debilitating disease.


Subject(s)
Hidradenitis Suppurativa , Humans , Autoantibodies , Lysine , Quality of Life , Pyruvaldehyde , Immunoglobulin G
15.
J Clin Med ; 13(1)2023 Dec 29.
Article in English | MEDLINE | ID: mdl-38202224

ABSTRACT

In autologous breast reconstruction, a sufficient flap volume is fundamental to restore breast shape and ensure an aesthetic outcome. After mastectomy, postoperative irradiation is regularly indicated in the oncological treatment algorithm. When administering radiation therapy after autologous reconstruction, the tissue transferred is inherently irradiated. Although there is evidence that points to a reduction in flap volume after adjuvant radiotherapy, the data have been contradicting and inconclusive. To address this anecdotal evidence, we performed a scoping review of the current literature that addresses the effect of radiotherapy on breast flap volume. Six two-armed studies, comprising a total of 462 patients, reported on the effect of adjuvant radiotherapy on free flap volume changes. Of those, two studies found a significant negative impact of radiotherapy on free flap volume, while the other four studies did not. Reported flap volume changes ranged from no change to a reduction of 26.2%, measured up to two years postoperatively. The selected studies contain varying patient numbers, follow-up timepoints, types of flaps, and measuring methods, contributing to a relatively high heterogeneity. While we present some evidence suggesting a significant impact of adjuvant radiotherapy on breast flap volume, future studies are needed to further investigate this potential correlation.

16.
Ann Plast Surg ; 89(6): 593-594, 2022 12 01.
Article in English | MEDLINE | ID: mdl-36416681

ABSTRACT

ABSTRACT: Modern medicine tends to provide comprehensive medical services based on disease or pathological features. As a result, the overlap between plastic surgery and other surgical departments greatly deepened. What was exclusively done by plastic surgeons are nowadays frequently practiced by other surgeons as well. Thus, generating confusion as to whether plastic surgery is an independent subject or a tool. Therefore, in this new era of modern medicine, it is necessary to reconsider the definition of plastic surgery.


Subject(s)
Plastic Surgery Procedures , Surgeons , Surgery, Plastic , Humans
17.
Acta Biomater ; 154: 641-649, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36261107

ABSTRACT

We previously described an immortalized, genetically-engineered human Mesenchymal stromal cell line to generate BMP2-enriched Chondrogenic Matrices (MB-CM), which after devitalization and storage could efficiently induce ectopic bone tissue by endochondral ossification. In order to increase the efficiency of MB-CM utilization towards engineering scaled-up bone structures, here we hypothesized that MB-CM can retain osteoinductive properties when combined with an osteoconductive material. We first tested different volumetric ratios of MB-CM:SmartBone® (as clinically used, osteoconductive reference material) and assessed the bone formation capacity of the resulting composites following ectopic mouse implantation. After 8 weeks, as little as 25% of MB-CM was sufficient to induce bone formation and fusion across SmartBone® granules, generating large interconnected bony structures. The same composite percentage was then further assessed in a scaled-up model, namely within an axially-vascularized, confined, ectopically prefabricated flap (0.8 cm3) in rats. The material efficiently induced the formation of new bone (31% of the cross-sectional area after 8 weeks), including bone marrow and vascular elements, throughout the flap volume. Our findings outline a strategy for efficient use of MB-CM as part of a composite material, thereby reducing the amount required to fill large spaces and enabling utilization in critically sized grafts, to address challenging clinical scenarios in bone reconstruction. STATEMENT OF SIGNIFICANCE: Most bone repair strategies rely either on osteconductive properties of ceramics and devitalized bone, or osteoinductive properties of growth factors and extracellular matrices (ECM). Here we designed a composite material made of a clinically accepted osteoconductive material and an off-the-shelf tissue engineered human cartilage ECM with strong osteoinductive properties. We showed that low amount of osteoinductive ECM potentiated host cells recruitment to form large vascularized bone structures in two different animal models, one being a challenging prefabricated bone-flap model targeting challenging clinical bone repair. Overall, this study highlights the use of a promising human off-the-shelf material for accelerated healing towards clinical applications.


Subject(s)
Osteogenesis , Tissue Engineering , Rats , Mice , Humans , Animals , Tissue Engineering/methods , Cartilage , Bone Regeneration , Chondrogenesis
18.
Bioengineering (Basel) ; 9(9)2022 Aug 24.
Article in English | MEDLINE | ID: mdl-36134958

ABSTRACT

Nerve injuries remain clinically challenging, and allografts showed great promise. Decellularized nerve allografts possess excellent biocompatibility and biological activity. However, the vast majority of decellularization protocols were established for small-size rodent nerves and are not suitable for clinical application. We aimed at developing a new method of decellularizing large-diameter nerves suitable for human transplantation. Repeated rounds of optimization to remove immunogenic material and preserve the extracellular structure were applied to the porcine sciatic nerve. Following optimization, extensive in vitro analysis of the acellular grafts via immunocytochemistry, immunohistology, proteomics and cell transplantation studies were performed. Large segments (up to 8 cm) of the porcine sciatic nerve were efficiently decellularized and histology, microscopy and proteomics analysis showed sufficient preservation of the extracellular matrix, with simultaneous consistent removal of immunogenic material such as myelin, DNA and axons, and axonal growth inhibitory molecules. Cell studies also demonstrated the suitability of these acellular grafts for 3D cell culture studies and translation to future large animal studies and clinical trials. By using non-human donors for peripheral nerve transplantation, significant drawbacks associated with the gold standard can be eliminated while simultaneously preserving the beneficial features of the extracellular matrix.

19.
Arch Plast Surg ; 49(4): 494-500, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35919555

ABSTRACT

Background Seroma formation is the most common donor site complication following autologous breast reconstruction, along with hematoma. Seroma may lead to patient discomfort and may prolong hospital stay or delay adjuvant treatment. The aim of this study was to compare seroma rates between the deep inferior epigastric perforator (DIEP), transverse musculocutaneous gracilis (TMG), and superior gluteal artery perforator (SGAP) donor sites. Methods The authors conducted a retrospective single-center cohort study consisting of chart review of all patients who underwent microsurgical breast reconstruction from April 2018 to June 2020. The primary outcome studied was frequency of seroma formation at the different donor sites. The secondary outcome evaluated potential prognostic properties associated with seroma formation. Third, the number of donor site seroma evacuations was compared between the three donor sites. Results Overall, 242 breast reconstructions were performed in 189 patients. Demographic data were found statistically comparable between the three flap cohorts, except for body mass index (BMI). Frequency of seroma formation was highest at the SGAP donor site (75.0%), followed by the TMG (65.0%), and DIEP (28.6%) donor sites. No association was found between seroma formation and BMI, age at surgery, smoking status, diabetes mellitus, neoadjuvant chemotherapy, or DIEP laterality. The mean number of seroma evacuations was significantly higher in the SGAP and the TMG group compared with the DIEP group. Conclusion This study provides a single center's experience regarding seroma formation at the donor site after microsurgical breast reconstruction. The observed rate of donor site seroma formation was comparably high, especially in the TMG and SGAP group, necessitating an adaption of the surgical protocol.

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