Functional Recellularization of Acellular Rat Liver Scaffold by Induced Pluripotent Stem Cells: Molecular Evidence for Wnt/B-Catenin Upregulation.

BACKGROUND: Liver transplantation remains the only viable therapy for liver failure but has a severely restricted utility. Here, we aimed to decellularize rat livers to form acellular 3D bio-scaffolds suitable for seeding with induced pluripotent cells (iPSCs) as a tool to investigate the role of Wnt/ß-catenin signaling in liver development and generation. METHODS: Dissected rat livers were randomly divided into three groups: I (control); II (decellularized scaffolds) and III (recellularized scaffolds). Liver decellularization was established via an adapted perfusion procedure and assessed through the measurement of extracellular matrix (ECM) proteins and DNA content. Liver recellularization was assessed through histological examination and measurement of transcript levels of Wnt/ß-catenin pathway, hepatogenesis, liver-specific microRNAs and growth factors essential for liver development. Adult rat liver decellularization was confirmed by the maintenance of ECM proteins and persistence of growth factors essential for liver regeneration. RESULTS: iPSCs seeded rat decellularized livers displayed upregulated transcript expression of Wnt/ß-catenin pathway-related, growth factors, and liver specification genes. Further, recellularized livers displayed restored liver-specific functions including albumin secretion and urea synthesis. CONCLUSION: This establishes proof-of-principle for the generation of three-dimensional liver organ scaffolds as grafts and functional re-establishment.

Adipose mesenchymal stem cells combined with platelet-rich plasma accelerate diabetic wound healing by modulating the Notch pathway.

BACKGROUND: Diabetic foot ulceration is a serious chronic complication of diabetes mellitus characterized by high disability, mortality, and morbidity. Platelet-rich plasma (PRP) has been widely used for diabetic wound healing due to its high content of growth factors. However, its application is limited due to the rapid degradation of growth factors. The present study aimed to evaluate the efficacy of combined adipose-derived mesenchymal stem cells (ADSCs) and PRP therapy in promoting diabetic wound healing in relation to the Notch signaling pathway. METHODS: Albino rats were allocated into 6 groups [control (unwounded), sham (wounded but non-diabetic), diabetic, PRP-treated, ADSC-treated, and PRP+ADSCs-treated groups]. The effect of individual and combined therapy was evaluated by assessing wound closure rate, epidermal thickness, dermal collagen, and angiogenesis. Moreover, gene and protein expression of key elements of the Notch signaling pathway (Notch1, Delta-like canonical Notch ligand 4 (DLL4), Hairy Enhancer of Split-1 (Hes1), Hey1, Jagged-1), gene expression of angiogenic marker (vascular endothelial growth factor and stromal cell-derived factor 1) and epidermal stem cells (EPSCs) related gene (ß1 Integrin) were assessed. RESULTS: Our data showed better wound healing of PRP+ADSCs compared to their individual use after 7 and 14 days as the combined therapy caused reepithelialization and granulation tissue formation with a marked increase in area percentage of collagen, epidermal thickness, and angiogenesis. Moreover, Notch signaling was significantly downregulated, and EPSC proliferation and recruitment were enhanced compared to other treated groups and diabetic groups. CONCLUSIONS: These data demonstrated that PRP and ADSCs combined therapy significantly accelerated healing of diabetic wounds induced experimentally in rats via modulating the Notch pathway, promoting angiogenesis and EPSC proliferation.

Oncoplastic Volume Replacement for Breast Cancer: Latissimus Dorsi Flap versus Thoracodorsal Artery Perforator Flap.

BACKGROUND: Volume replacement oncoplastic breast techniques have become one of the standard lines in the treatment of early breast cancer. They have better cosmetic outcome and patient satisfaction. Latissimus dorsi (LD) flap is one of the most commonly used flaps for these techniques. Although it shows satisfactory surgical outcomes, postoperative shoulder dysfunction is an obvious drawback. The aim of this study was to compare LD flap with thoracodorsal artery perforator (TDAP) flap after breast-conserving surgery regarding surgical outcomes, patient satisfaction, and impact on shoulder function. METHODS: The study included 42 adult female patients with early breast cancer who were eligible for conservative breast surgery and immediate breast reconstruction. Patients were divided into 2 equal groups: group A where patients underwent immediate reconstruction using LD flap and group B where patients underwent reconstruction using TDAP flap. Follow-up was designed for 12 months for early outcome, patient satisfaction, and shoulder functions. RESULTS: The mean age of the included patients in group A and group B was 40.95 ± 5.06 and 40.33± 5.25 years, respectively. There was no significant difference in flap dimensions, postoperative complications, or cosmetic outcome in both groups. However, significantly less shoulder dysfunction was documented in cases of TDAP compared to LD flap at 3, 6, and 12 months postoperatively. CONCLUSIONS: TDAP flap is as reliable a technique as LD flap regarding the feasibility, postoperative complications, and the cosmetic outcome with significantly better functional outcome of the shoulder.

Functional and Aesthetic Outcomes of Reconstruction of Soft-Tissue Defects of the Heel with Free Flap.

OBJECTIVE: To evaluate functional and aesthetic outcomes of the reconstruction of soft-tissue defects of the heel with microsurgical techniques using a free radial forearm flap and an anterolateral thigh flap. PATIENTS AND METHODS: The study included 25 patients, 15 males and 10 females, with a mean age of 34.3 ± 10.4 years, with soft-tissue defects of the heel. Of them, 11 patients whose defects were of size between 5 and 10 cm in their largest dimension were treated using a free radial forearm flap, and 14 patients whose defects were of size larger than 10 cm in their largest dimension were treated using a free anterolateral thigh flap.Post-operatively, avoidance of weight-bearing and walking was required for 8 to 10 weeks. At the end of the follow-up, all patients underwent functional, aesthetic and sensation evaluation in addition to assessment of patient satisfaction. RESULTS: The median follow-up period was 24 months. The causes of the defect were trauma (14 patients), neuropathic ulcer (8 patients) and neoplasia (3 patients). The size of the defect ranged from 5 × 6 cm to 14 × 24 cm. Four patients had calcaneal fracture. By the end of the follow-up period, 21 cases showed complete success, whereas 2 flaps failed, one in each flap type, and the remaining two flaps showed partial loss of the edges (anterolateral thigh flaps). Failure was due to venous congestion (one patient) and ischaemia (one patient). Eighteen patients were satisfied with their aesthetic appearance, functional outcome and flap sensation. CONCLUSION: Reconstruction of large heel defects, using radial forearm and anterolateral thigh free flaps, provides acceptable functional and aesthetic outcomes.

Outcome of Pedicled Thoracodorsal Artery Perforator Flap in the Surgical Treatment of Stage II and III Hidradenitis Suppurativa of Axilla.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory disease affecting the apocrine glands of the axillary, groin, and mammary regions with significant physical and psychosocial sequelae. Surgical excision of the affected tissue is the criterion standard treatment. Advanced cases of axillary HS are associated with high rates of recurrence and require extensive surgical resection with challenging reconstruction associated with risk of postoperative complications. The most effective method for reconstruction of the axilla after excision of HS is yet to be identified. OBJECTIVES: The aim of the study was to evaluate the results of the use of pedicled thoracodorsal artery perforator (TDAP) flap as a method of reconstruction for axillary efect result from wide surgical excision as a line of treatment for stage II and III HS of the axilla. PATIENT AND METHODS: The study included 20 patients with stage II and III (Hurley staging system) HS of the axilla, 18 male and 2 women treated by wide local excision and reconstruction by rotational TDAP flap. At the end of follow-up, outcome is judged by complete remission of disease, comparing preoperative shoulder function (using Constant-Murley shoulder outcome score), and quality of life (using dermatology life quality index) with postoperative results after 1 year, plus durability of reconstruction, donor site morbidity, overall aesthetic outcome, and patient's satisfaction. RESULTS: The mean ± SD follow-up period was 30 ± 5.2 months (range = 12-60 months). Four patients (20%) were treated for their right side, 8 patients (40%) for their left side, and 8 patients (40%) were treated bilaterally, so we perform 28 operations for 20 patients. The treated patients with stage II disease were 16 (57.14%) and with stage III disease were 12 (42.85%). The size of the defects was usually approximately 10 × 15 cm. By the end of follow-up period, all patient showed complete remission of the disease with improvement in both shoulder function and quality of life, whereas 1 flap (3.57%) was complicated by bleeding treated by reoperation, 2 flaps (7.14%) complicated by wound infection that was treated conservatively, 3 other flaps (10.71%) showed wide scare at insight of the flaps, and 1 flap (3.57%) developed hypertrophic scare at donor site of the flap. CONCLUSIONS: Surgical treatment of stage II and III HS of axilla and reconstruction by rotational TDAP flap provides good aesthetic and functional results with 100% success rate in eradicating and complete remission of the disease during follow-up period and accepted complication rate.