Vasculogenic Potency of Bone Marrow- and Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells Results in Differing Vascular Network Phenotypes in a Microfluidic Chip.

The vasculature is an essential, physiological element in virtually all human tissues. Formation of perfusable vasculature is therefore crucial for reliable tissue modeling. Three-dimensional vascular networks can be formed through the co-culture of endothelial cells (ECs) with stromal cells embedded in hydrogel. Mesenchymal stem/stromal cells (MSCs) derived from bone marrow (BMSCs) and adipose tissue (ASCs) are an attractive choice as stromal cells due to their natural perivascular localization and ability to support formation of mature and stable microvessels in vitro. So far, BMSCs and ASCs have been compared as vasculature-supporting cells in static cultures. In this study, BMSCs and ASCs were co-cultured with endothelial cells in a fibrin hydrogel in a perfusable microfluidic chip. We demonstrated that using MSCs of different origin resulted in vascular networks with distinct phenotypes. Both types of MSCs supported formation of mature and interconnected microvascular networks-on-a-chip. However, BMSCs induced formation of fully perfusable microvasculature with larger vessel area and length whereas ASCs resulted in partially perfusable microvascular networks. Immunostainings revealed that BMSCs outperformed ASCs in pericytic characteristics. Moreover, co-culture with BMSCs resulted in significantly higher expression levels of endothelial and pericyte-specific genes, as well as genes involved in vasculature maturation. Overall, our study provides valuable knowledge on the properties of MSCs as vasculature-supporting cells and highlights the importance of choosing the application-specific stromal cell source for vascularized organotypic models.

Comparison of Different Techniques in Latissimus Dorsi Breast Reconstruction: Plain, Immediately Lipofilled, and Implant Enhanced.

BACKGROUND: The latissimus dorsi (LD) flap is still a popular choice for breast reconstruction. Plain LD provides a good option for women with small breasts, but with bigger breasts, the problem is insufficient volume. Traditionally, implants have been inserted to improve the volume, but because of problems associated with them, the use of fat grafting has gained popularity. Increased numbers of reports considering also immediate lipofilling have been published. This study aimed to evaluate and compare different techniques in LD reconstruction in association with complications, number of further operations, and duration of reconstructive process. METHODS: A retrospective review of patients who had undergone LD reconstruction between 2008 and 2019 was performed. Demographic and operative features, complications, and the duration of reconstruction process were analyzed. RESULTS: A total of 291 LD flaps were performed in 283 women, including 161 (55%) implant enhanced, 73 (25%) immediate lipofilled, and 57 (20%) plain flaps. Of these, 84% were delayed reconstructions. The median volume of immediately injected fat was 155 mL (range, 50-296 mL) and inserted implant 185 mL (range, 80-420 mL). Of plain LDs, 75% did not need further operations compared with 63% of implant and 49% of lipofilling groups (P < 0.001). The median duration of reconstructive process was 10 months (range, 4-86 months) in plain, 13 months (range, 5-58 months) in implant, and 18 months (range, 5-80 months) in lipofilling group (P < 0.002). No significant differences were observed in overall complication rates between groups (P = 0.228). Most of the complications were minor, seroma being the most common. Of major complications, plain flaps were most commonly associated with donor site problems, lipofilling group with partial flap necrosis, and implant enhanced with deep infections in the breast. Shoulder problem was observed in 21 patients (7%) with no significant difference between groups (P = 0.395). CONCLUSIONS: Latissimus dorsi flap is a versatile and safe breast reconstruction method, because it is associated most commonly only with minor complications. Careful patient selection is important when choosing between different techniques. This can have an impact on the number of further operations needed and the duration of reconstruction process. Immediate lipofilling is a safe technique to avoid the use of implant and allow fully autologous reconstruction.

Is there any difference in perioperative characteristics or postoperative complications between overweight, normal-weight and obese patients in delayed DIEP reconstructions?

Increased number of overweight and obese women are seeking breast reconstruction. Studies have demonstrated that obese experience increased rates of complications, but less data is available considering overweight patients. We analyzed the impact of body mass index (BMI) on perioperative characteristics and complications in unilateral delayed deep inferior epigastric perforator flap (DIEP) reconstructions. The records of patients with DIEP reconstruction performed between 2014 and 2020, were retrospectively analyzed. Patients were categorized into obese (BMI ≥30), overweight (BMI 25.0-29.9), and normal-weight groups (BMI <25). Patient characteristics (age, comorbidity, radiation, abdominal surgery, ASA category, and smoking), perioperative characteristics (length of operation, blood loss, vasoactive drugs, fluid administration, and urine output), and postoperative complications were recorded. The study included 308 patients. Of these, 104 (34%) were normal-weighted, 142 (46%) overweight and 62 (20%) obese. Among patients with BMI ≥ 25, blood loss increased (p = 0.002) and the length of operation tended to be longer (p = 0.072). No between-groups difference existed in fluid administration (p = 0.319), urine output (p = 0.425), or use of vasoactive drugs (p = 0.815). There was no statistically significant difference in overall complications (p = 0.122) between BMI groups. Blood loss >150ml was associated with both minor and major complications (p = 0.022). Greater BMI moderated with the radiation therapy for higher risk of minor complications (OR 42.0, 95%CI 3.54-49.7, p = 0.003). We conclude that greater BMI alone is not associated with a higher overall complication rate, but both overweight and obesity may be moderators for other risk factors.

Myocardin-Related Transcription Factor A (MRTF-A) Regulates the Balance between Adipogenesis and Osteogenesis of Human Adipose Stem Cells.

Previous studies have demonstrated that myocardin-related transcription factor A (MRTF-A) generates a link between the dynamics of the actin cytoskeleton and gene expression with its coregulator, serum response factor (SRF). MRTF-A has also been suggested as a regulator of stem cell differentiation. However, the role of MRTF-A in human mesenchymal stem cell differentiation remains understudied. We aimed to elucidate whether MRTF-A is a potential regulator of human adipose stem cell (hASC) differentiation towards adipogenic and osteogenic lineages. To study the role of MRTF-A activity in the differentiation process, hASCs were cultured in adipogenic and osteogenic media supplemented with inhibitor molecules CCG-1423 or CCG-100602 that have been shown to block the expression of MRTF-A/SRF-activated genes. Our results of image-based quantification of Oil Red O stained lipid droplets and perilipin 1 staining denote that MRTF-A inhibition enhanced the adipogenic differentiation. On the contrary, MRTF-A inhibition led to diminished activity of an early osteogenic marker alkaline phosphatase, and export of extracellular matrix (ECM) proteins collagen type I and osteopontin. Also, quantitative Alizarin Red staining representing ECM mineralization was significantly decreased under MRTF-A inhibition. Image-based analysis of Phalloidin staining revealed that MRTF-A inhibition reduced the F-actin formation and parallel orientation of the actin filaments. Additionally, MRTF-A inhibition affected the protein amounts of α-smooth muscle actin (α-SMA), myosin light chain (MLC), and phosphorylated MLC suggesting that MRTF-A would regulate differentiation through SRF activity. Our results strongly indicate that MRTF-A is an important regulator of the balance between osteogenesis and adipogenesis of hASCs through its role in mediating the cytoskeletal dynamics. These results provide MRTF-A as a new interesting target for guiding the stem cell differentiation in tissue engineering applications for regenerative medicine.

Differences in Risk Factors for Melanoma in Young and Middle-aged Higher-risk Patients.

BACKGROUND/AIM: Differences in risk factors for melanoma between young adults (18-39 years) and middle-aged (40-60 years) are not well documented. In this study, we aimed to determine differences in risk factors and characteristics of melanoma between these groups. PATIENTS AND METHODS: This retrospective study is a review on 330 patients, including 250 middle-aged and 80 young adults, during the period 2006-2016 in the Tampere university hospital, in Finland. RESULTS: Forty-one per cent of middle-aged and 47% of young adults were defined as higher-risk patients. High nevus count was the most common host risk factor in both groups. Young were more likely to have a family history of melanoma. Middle-aged had more often excessive intermittent sun exposure and a history of sunburn. Host risk characteristics were less commonly associated with thicker melanomas. CONCLUSION: A high number of patients have host risk factors for melanoma. Several differences exist in risk factors and characteristics of melanomas between young adults and middle-aged patients.

Bioactive glass ions for in vitro osteogenesis and microvascularization in gellan gum-collagen hydrogels.

Lack of bone grafts appeals for bone augmentation solutions. We aimed at osteogenic differentiation of human adipose stem cells (hASCs) and microvascularization in coculture with human umbilical vein endothelial cells (HUVECs) embedded in three-dimensional (3D) gellan gum (GG) and collagen type I (COL) hydrogel mixture. We compared endothelial growth medium-2 (EGM-2) and bioactive glass extract-based endothelial and osteogenic medium (BaG EM-OM) for vascularized bone-like graft development in vitro. Cell viability, cell number, and osteogenic and endothelial gene expression were analyzed. Mineralized hydroxyapatite residues, immunocytochemical staining of endothelial marker CD31 production and late osteogenic marker osteocalcin were imaged. With both media, good cell viability was observed within 3D hydrogel. EGM-2 condition induced significantly higher cell number compared to BaG EM-OM condition at both 7 and 14 days. Interestingly, both media supported osteogenic as well as endothelial marker gene expression. Moreover, formation of reticulated cellular structures was observed in both EGM-2 and BaG EM-OM conditions. However, hydroxyapatite mineralization and strong osteocalcin staining were detected only in BaG EM-OM condition. Importantly, strong production of CD31 and elongated tube-like structures were apparent in EGM-2 culture alone. In conclusion, we demonstrated efficient hASC osteogenic differentiation and microvessel-like network formation in coculture with HUVECs.

Nanofibrillar cellulose wound dressing supports the growth and characteristics of human mesenchymal stem/stromal cells without cell adhesion coatings.

BACKGROUND: In the field of regenerative medicine, delivery of human adipose-derived mesenchymal stem/stromal cells (hASCs) has shown great promise to promote wound healing. However, a hostile environment of the injured tissue has shown considerably to limit the survival rate of the transplanted cells, and thus, to improve the cell survival and retention towards successful cell transplantation, an optimal cell scaffold is required. The objective of this study was to evaluate the potential use of wood-derived nanofibrillar cellulose (NFC) wound dressing as a cell scaffold material for hASCs in order to develop a cell transplantation method free from animal-derived components for wound treatment. METHODS: Patient-derived hASCs were cultured on NFC wound dressing without cell adhesion coatings. Cell characteristics, including cell viability, morphology, cytoskeletal structure, proliferation potency, and mesenchymal cell and differentiation marker expression, were analyzed using cell viability assays, electron microscopy, immunocytochemistry, and quantitative or reverse transcriptase PCR. Student's t test and one-way ANOVA followed by a Tukey honestly significant difference post hoc test were used to determine statistical significance. RESULTS: hASCs were able to adhere to NFC dressing and maintained high cell survival without cell adhesion coatings with a cell density-dependent manner for the studied period of 2 weeks. In addition, NFC dressing did not induce any remarkable cytotoxicity towards hASCs or alter the morphology, proliferation potency, filamentous actin structure, the expression of mesenchymal vimentin and extracellular matrix (ECM) proteins collagen I and fibronectin, or the undifferentiated state of hASCs. CONCLUSIONS: As a result, NFC wound dressing offers a functional cell culture platform for hASCs to be used further for in vivo wound healing studies in the future.

Tibial shaft fractures in Finland between 1997 and 2014.

INTRODUCTION: Tibial shaft fracture is common, accounting for 2% of all adult fractures. Large epidemiological follow ups are lacking and previous studies have shown great variation in incidence rates and trends. The aim of this population-based nationwide study was to analyze all tibial shaft fractures in Finland in 1997-2014 and to provide an update on current epidemiological data. PATIENTS AND METHODS: Patient data was collected from the Finnish National Hospital Discharge Register (NHDR) from 1997 to 2014. The study covered the entire adult (18 years and older) population. The primary outcome was the annual number of hospitalization due to a fresh tibial shaft fracture. RESULTS: A total of 14,150 patients with a fresh tibial shaft fracture were identified during the 18-year study period. The total fracture incidence decreased from 27.3 per 100,000 person-years in 1997 to 13.5 per 100,000 person-years in 2014. In men, the incidence was 34.9 in 1997 vs. 15.6 in 2014, while in women the corresponding numbers were 20.2 in 1997 vs. 11.5 in 2014. CONCLUSIONS: The incidence of tibial shaft fractures has markedly decreased in Finland between 1997 and 2014, mainly because of a declining trend in the incidence of fall-induced low-energy fractures. Reasons for this development are uncertain and therefore more comprehensive population-based epidemiological studies are needed to reveal the factual reasons behind the decrease.

Bioactive glass ions induce efficient osteogenic differentiation of human adipose stem cells encapsulated in gellan gum and collagen type I hydrogels.

BACKGROUND: Due to unmet need for bone augmentation, our aim was to promote osteogenic differentiation of human adipose stem cells (hASCs) encapsulated in gellan gum (GG) or collagen type I (COL) hydrogels with bioactive glass (experimental glass 2-06 of composition [wt-%]: Na2O 12.1, K2O 14.0, CaO 19.8, P2O5 2.5, B2O3 1.6, SiO2 50.0) extract based osteogenic medium (BaG OM) for bone construct development. GG hydrogels were crosslinked with spermidine (GG-SPD) or BaG extract (GG-BaG). METHODS: Mechanical properties of cell-free GG-SPD, GG-BaG, and COL hydrogels were tested in osteogenic medium (OM) or BaG OM at 0, 14, and 21 d. Hydrogel embedded hASCs were cultured in OM or BaG OM for 3, 14, and 21 d, and analyzed for viability, cell number, osteogenic gene expression, osteocalcin production, and mineralization. Hydroxyapatite-stained GG-SPD samples were imaged with Optical Projection Tomography (OPT) and Selective Plane Illumination Microscopy (SPIM) in OM and BaG OM at 21 d. Furthermore, Raman spectroscopy was used to study the calcium phosphate (CaP) content of hASC-secreted ECM in GG-SPD, GG-BaG, and COL at 21 d in BaG OM. RESULTS: The results showed viable rounded cells in GG whereas hASCs were elongated in COL. Importantly, BaG OM induced significantly higher cell number and higher osteogenic gene expression in COL. In both hydrogels, BaG OM induced strong mineralization confirmed as CaP by Raman spectroscopy and significantly improved mechanical properties. GG-BaG hydrogels rescued hASC mineralization in OM. OPT and SPIM showed homogeneous 3D cell distribution with strong mineralization in BaG OM. Also, strong osteocalcin production was visible in COL. CONCLUSIONS: Overall, we showed efficacious osteogenesis of hASCs in 3D hydrogels with BaG OM with potential for bone-like grafts.

Clinical results and quality of life after reconstruction following sacrectomy for primary bone malignancy.

BACKGROUND: Sacrectomy is a rare and demanding surgical procedure that results in major soft tissue defects and spinopelvic discontinuity. No consensus is available on the optimal reconstruction algorithm. Therefore, the present study evaluated the results of sacrectomy reconstruction and its impact on patients' quality of life (QOL). METHODS: A retrospective chart review was conducted for 21 patients who underwent sacrectomy for a primary bone tumour. Patients were divided into groups based on the timing of reconstruction as follows: no reconstruction, immediate reconstruction or delayed reconstruction. QOL was measured using the EQ-5D instrument before and after surgery in patients treated in the intensive care unit. RESULTS: The mean patient age was 57 (range 22-81) years. The most common reconstruction was gluteal muscle flap (n = 9) and gluteal fasciocutaneous flap (n = 4). Four patients required free-tissue transfer, three latissimus dorsi flaps and one vascular fibula bone transfer. No free flap losses were noted. The need for unplanned re-operations did not differ between groups (p = 0.397), and no significant differences were found for pre- and post-operative QOL or any of its dimensions. DISCUSSION: Free flap surgery is reliable for reconstructing the largest sacrectomy defects. Even in the most complex cases, surgery can be safely staged, and final reconstruction can be carried out within 1 week of resection surgery without increasing peri­operative complications. Sacrectomy does not have an immoderate effect on the measured QOL.

Modern postoperative monitoring of free flaps.

PURPOSE OF REVIEW: Flap failure in microvascular reconstruction is a costly complication with total flap loss being the worst-case scenario. With the aim to rapidly identify a postoperative circulatory problem, some susceptible flaps can be saved by careful clinical monitoring or by various technical monitoring methods. In head and neck surgery, where the flaps are often buried and difficult to monitor clinically, a reliable technical monitoring method would be useful. A broad range of different techniques are in use varying according to practical and personal preferences among clinics and surgeons. However, no evidence for any particular technique being superb has emerged. We review reports of some frequently used and modern free flap monitoring techniques. RECENT FINDINGS: Clinical monitoring is still the gold standard to which other techniques are compared to. Laser Doppler flowmetry and near-infrared spectroscopy have been reported to identify early circulatory problems, but both techniques are not well suited for buried flaps. Implantable Doppler, flow coupler, partial tissue oxygen pressure and microdialysis are invasive monitoring methods suitable for buried flaps. SUMMARY: More research with practical and clinically relevant parameters, that is flap salvage rate, false positive rate and cost-efficiency are needed before objective comparisons between different monitoring techniques can be made.

The Effect of Norepinephrine and Dopamine on Radial Forearm Flap Partial Tissue Oxygen Pressure and Microdialysate Metabolite Measurements: A Randomized Controlled Trial.

BACKGROUND: Patients undergoing ablative and reconstructive head and neck surgery with a microvascular flap have multiple factors that potentially decrease postoperative mean arterial pressure, which may endanger flap survival. The safety of vasopressor use has long been a topic of discussion. The authors analyzed the effect of vasopressors on microvascular flap perfusion after head and neck cancer reconstruction. METHODS: A total of 27 patients were enrolled in a randomized, controlled, clinical trial. A microvascular radial forearm flap was used for reconstruction. Patients were allocated into one of three groups: dopamine, norepinephrine, and control. The intervention groups received the vasoactive drug, aiming to maintain the mean arterial pressure between 80 and 90 mmHg. Normovolemia was maintained according to central venous pressure. Flap perfusion was monitored with continuous tissue partial pressure of oxygen and microdialysate metabolite (lactate-to-pyruvate ratio) measurements. RESULTS: No adverse effects were observed, and postoperative recovery was free of complications in all groups. Neither the lactate-to-pyruvate ratio nor continuous tissue partial pressure of oxygen values differed significantly between groups during the first 24 hours of the vasoactive drug infusion period or during the 72-hour follow-up. CONCLUSIONS: Norepinephrine and dopamine are safe and effective vasopressors for use during the postoperative period following head and neck cancer surgery with microvascular reconstruction. Dopamine should be used with caution, however, because of the risk of side effects. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Utilization of Three-Dimensional Computer-Aided Preoperative Virtual Planning and Manufacturing in Maxillary and Mandibular Reconstruction with a Microvascular Fibula Flap.

BACKGROUND: The aim of this study was to analyze the effects of computer-aided three-dimensional virtual planning and the use of customized cutting guides in maxillary and mandibular reconstruction with a microvascular fibula flap. METHODS: Patients (n = 17) undergoing free fibula flap (n = 18) reconstruction of the maxilla (n = 2) or mandible (n = 15) from January 2012 through March 2014 were enrolled in the study. Preoperatively, patients underwent high-resolution computed tomography of the maxillofacial and lower leg regions. Three-dimensional virtual planning of the resection and reconstruction was performed. Customized cutting guides for maxillary/mandibular resections and fibular osteotomies, and prebend plates were manufactured. Demographic data, surgical factors, and perioperative and postoperative results were evaluated. RESULTS: Sixteen patients had malignant disease and one had benign disease. Sixteen of the flaps were osteomuscular and two were osteomusculocutaneous. Mean ischemia time was 99 minutes and mean operative time was 542 minutes. The flaps fitted into the defects precisely and no bone grafts were needed. Mean length of the fibula flap was 74 mm and the mean number of segments in the flap was 2.1. CONCLUSION: Three-dimensional computer-aided preoperative virtual planning allowed for precise planning of the tumor resection and size of the fibula flap, the number and placement of the osteotomies needed, and the manufacture of customized cutting guides. Fibular shaping is easier and faster, which may decrease the ischemia time and total operative time. Exact placement of the flap in the defect may facilitate restoration of the anatomic shape and ossification.

[Surgery of the breast on transgender persons]. / Transsukupuolisten rintaleikkaukset.

For a female-to-male transgender person, mastectomy is the most important procedure making the social interaction easier. Along with the size of the breasts, the quantity and quality of skin will influence the selection of surgical technique. Although complications are rare, corrective surgery is performed for as many as 40% of the patients. Of male-to-female transsexual persons, 60 to 70% opt for breast enlargement. Breast enlargement can be carried out by using either silicone implants or fat transplantation. Since the surgical procedures on breasts are irreversible, their implementation requires confirmation of the diagnosis of transsexualism by a multidisciplinary team.

Primary flap reconstruction of tissue defects after sarcoma surgery enables curative treatment with acceptable functional results: a 7-year review.

BACKGROUND: Sarcomas, a heterogeneous group of tumors, are challenging to treat and require multidisciplinary cooperation and planning. We analyzed the efficacy of flap reconstruction in patients with bone and soft tissue sarcoma. METHODS: Patient charts and operative records were retrospectively reviewed from January 2006 through October 2013 to identify sarcoma patient characteristics, postoperative complications, revisions, recurrences, and survival. Pedicled and/or free flap reconstruction was performed in 109 patients. Flap selection was based on defect size, and exposure of anatomically critical structures or major orthopedic implants. RESULTS: Of 109 patients, 71 (65.1 %) were men, and mean age was 56.4 years. Tumors most frequently located in a lower extremity (38.7 %). Primary sarcomas comprised 79.2 % and recurrences occurred in 18.9 %. Wide resection was performed for 65.7 %, and there were 10 planned amputations combined with flap reconstruction. A total of 111 tumors received 128 flaps: 76 pedicled flaps, 42 free flaps, and 5 combined (10 total) pedicled + free-flaps. The success rate was 94 % for the pedicled flap group, 97 % for the free-flap group, and 100 % for the pedicle + free-flap group. Of 35 patients, 5 developed deep prosthetic infections. Only one amputation due to disease progression was performed. Satisfactory functional outcome was achieved in 69 %. Survival rate during a mean (standard deviation) 3(2) year follow-up was 83.5 %. CONCLUSIONS: Primary flap reconstruction after sarcoma surgery satisfies oncologic goals. Large tumors in difficult areas can be removed and complete tumor resection achieved. Our findings indicate a high survival rate after sarcoma surgery utilizing flap reconstruction and a low recurrence rate.

No need to cut the nerve in LD reconstruction to avoid jumping of the breast: a prospective randomized study.

BACKGROUND AND AIM: It has been shown that the myocutaneous latissimus dorsi flap volume and consistency remain mainly the same regardless the nerve is cut or not in breast reconstruction. It is controversial how big an impact the flap innervation has on the muscle activity of the flap. The aim of the study was to prospectively evaluate the influence of latissimus dorsi flap innervation on the functional and aesthetic outcome of delayed breast reconstruction. METHODS: Between 2007 and 2008, 28 breast reconstructions were performed and randomly divided into denervation group (surgical denervation by excision of 1 cm of proximal thoracodorsal nerve, n=14) and innervation group (thoracodorsal nerve saved intact, n=14). Patients were clinically evaluated and a questionnaire considering functional and aesthetic outcome was filled 1-year after operation. Muscular twitching, pain, tightness, shape and symmetry of the breasts were evaluated. In addition, the mobility of the shoulder joint on the operated side was evaluated and the patients self-estimated the activities of daily living. RESULTS: There was no significant difference in latissimus dorsi flap twitching, pain and tightness of the breast and symmetry and shape of the breasts between denervated and innervated groups. The shoulder joint mobility was not found to be changed significantly in either of the groups and there were no limitations in activities of daily living. CONCLUSIONS: Thoracodorsal nerve division or preservation does not significantly affect muscle contraction activity of the latissimus dorsi flap and distortion of the breast when latissimus dorsi muscle humeral insertion is also detached. Therefore, both cutting and saving the nerve are justified in latissimus dorsi flap breast reconstruction depending on whether the humeral insertion of the muscle is preserved intact or divided and the flap islanded. The study shows that there is no tangible benefit in dividing the nerve when the flap is islanded. Clinical trial has been registered in public trials registry. Trial registry name is 'The significance of latissimus dorsi flap innervation in delayed breast reconstruction'. Registration number is NCT01239524 and URL is https://register.clinicaltrials.gov.

Skeletal muscle injury and repair: the effect of disuse and denervation on muscle and clinical relevance in pedicled and free muscle flaps.

Skeletal muscle is prone to injury upon trauma or nerve damage. In reconstructive surgery, it is an interesting spare part. Fortunately, skeletal muscle is capable of extensive regeneration. Satellite cells, quiescent myogenic precursor cells, become activated following muscle injury: they divide and form myoblasts, fuse into myotubes, and finally mature to myofibers. Denervation in muscle or muscle flaps leads to myofiber atrophy, fibrosis, and fatty tissue infiltration. Experiments show that muscle flaps that are reinnervated also display a fair amount of atrophy. Muscle mass is better preserved after motor innervation than sensory innervation. Clinical data imply that innervation of the muscle flap does not improve volume preservation significantly compared with denervated flaps. In addition, the softness of the flap remains the same whether the flap is innervated or not. Innervation of the flap seems to be needed only if functional muscle reconstruction is the goal. If reinnervation is successful but the muscle is kept short, disuse atrophy will still proceed. Muscle flaps should therefore be placed into their original length.