Pre-expanded Muscle-sparing Latissimus Dorsi Flaps for Reconstruction of Severe Scar Contractures on the Anterior Chest

Objective To investigate the utility of pre-expanded muscle-sparing latissimus dorsi flaps in the reconstruction of deformities secondary to severe scar contractures on the anterior chest.Methods The function of the latissimus dorsi was preserved with blood supply from the main or lateral branch of the thoracodorsal artery.The entire treatment period was divided into two stages,during which segmental latissimus dorsi flaps were pre-expanded in stage I and anterior chest scar deformities were reconstructed in stage II.During stage I,the musculocutaneous perforators arising from the lateral branch of the thoracodorsal artery were determined by ultrasound preoperatively;the flap design included the anterior segment of the latissimus dorsi supplied by the musculocutaneous perforators from the lateral branch;and a tissue expander was placed following flap dissection and then infused with saline intermittently for 4–6 months.In stage II,the chest scars were excised,and breast tissues were repositioned;the continuity of the medial branch of the thoracodorsal nerve to the muscle was preserved when reconstruction was performed using the segmental latissimus dorsi flaps supplied by the main or lateral branch of the thoracodorsal artery.Results From October 2010 to October 2019,21 patients(on 24 sides)underwent reconstructive procedures for extensive scar contractures on the anterior chest.All flaps survived,and their donor sites were sutured directly.During a follow-up of 3 months to 8 years,the flaps became soft and exhibited color similar to that of the adjacent tissues.The limited neck and shoulder movements improved,and postoperatively,all female patients were satisfied with the shape of their breasts.Additionally,neither apparent weakening on the adduction,internal rotation,or extension strength of the shoulder joint on the affected side nor marked depression deformity in the back was observed.Conclusion Pre-expanded muscle-sparing latissimus dorsi flaps with blood supply from the main or lateral branch of the thoracodorsal artery proved to be a desirable option for the reconstruction of extensive scar contractures on the anterior chest.

Matrix Softening Induces Inflammatory Signals of Endothelial Cells

Vascular diseases such as atherosclerosis involve the change of the rigidity in the blood vessel wall. There is evidence that the changes in the blood vessel rigidity may affect the various functions of the cells in the blood vessel, including endothelial cells (ECs) and the smooth muscle cells. On the other hand, blood vessel-on-a-chip has become an emerging research field for dis-ease modeling. However, the effect of material rigidity on blood vessel remodeling is not well understood. Hereby, an in vitro culture system with the culture substrates matching the rigidity of vessel wall mimicking the condition of healthy (normal) or lipid deposition (soft) were prepared. The stiffness of the substrates was confirmed by atomic force microscope. Although no significant difference was observed in EC morphology, the expression levels of the pro-inflammatory cytokines, including interleukin 6 (IL6), tumor necrosis factor α (TNF-α) and interleukin 1β (IL1β), were dramatically induced by soft substrate. Consistently, the inflammation-related JNK signaling was also activated. In addition, the expression level of microRNA-146a (miR-146a) was significantly decreased. Accordingly, mRNA expression level of TNF receptor associated factor 6 (TRAF6), the direct target of miR-146a, was significantly increased. In summary, these findings provide new insight into the matrix rigidity effect on ECs;while engineering the blood vessel model in vitro, matrix with proper rigidity can be carefully tailor to mimic ECs either in a quiescent or an inflammation state.

Functionalized Asymmetric Poly (Lactic Acid)/Gelatin Composite Membrane for Guided Periodontal Tissue Regeneration

Aim: Periodontitis is caused by chronic gingival inflammation and affects a large population in the world. Although guided tissue regeneration (GTR) therapy has been proven to be an effective treatment, the deficiency in the symmetrical design of all the GTR membrane in the market leaves large space for improvement. Therefore, we designed a novel asymmetrical bi-layer PLA/gelatin composite membrane for treating periodontitis. Methods: The PLA side was fabricated by electrospinning with metronidazole (MNA) pre-mixed with the PLA solution. The gelatin side containing bioglass (BG) 45S5 was fabricated with freeze-drying process and cross-linked with PLA membrane. The bio-compatibility of the membrane was evaluated in vitro using NIH3T3 cells. The releasing of MNA was measured by spectrophotometer. The bioactivity of the membrane was evaluated by hydroxyapatite (HA) deposit and determined by FTIR spectrometer. The ionic concentration of Ca2+ and was measured by ICPOES. The expression of the osteogenesis makers was determined by qRT-PCR. Results: The bi-layer PLA/gelatin composite membrane is biocompatible and bioactive. The releasing of MNA can rapidly reach the anti-bacterial effective concentration. Interestingly, the incorporation of MNA modulated the degradation rate of PLA scaffold to meet the requirement of tissue regeneration. Meanwhile, the embedding of the BG powder in the gelatin porous layer provided a favorable Ca2+ and ion environment for the regeneration of the alveolar bone tissue. Conclusions: Taken together, this bi-layer GTR membrane is closer to the physiological structure of the periodontal. The addition of MNA and BG makes it more powerful in treating periodontitis. Moreover, this research provides an example of biomimetic design in fabricating biomaterial for clinical applications.

Biomaterial Surface Can Modify HUVEC Morphology and Inflammatory Response by Regulating MicroRNA Expression

Vascular inflammation is an important process which contributes to the pathogenesis of many cardiovascular diseases, such as atherosclerosis. MicroRNAs (miRNAs) have been revealed as novel regulators of vascular inflammation. Prior researches had shown that alterations in gene expression of human umbilical vein endothelial cells (HUVECs) associated with topo-graphic cues. Here, we showed that poly (dimethyl siloxane) (PDMS) substrate of 10 μm width and 3 μm depth parallel microgrooves on the surface could significantly upregulate the expression of anti-inflammatory microRNAs, miR-146a and miR-181b. In addition, the results also showed that TRAF6 and importin-α3, target of miR-146a and miR-181b, respectively, were both down-regulated (P < 0.05 and P < 0.001, respectively). The expression levels of the inflammation related proteins were all significantly decreased, including VCAM-1 (P < 0.05), ICAM-1 (P < 0.001), E-selectin (P < 0.001), and MCP-1 (P < 0.05). The adhesion of the mononuclear cell line, THP-1, was significantly decreased (P < 0.05). The results revealed that morphology modified HUVEC can modulate miR-146a and miR-181b and their downstream biological functions such as decreasing inflammation, suggesting that surface microtopology may affect vascular inflammation in the setting of cardiovascular disease. These interesting findings will facilitate the optimal design of microstructured materials in tissue engineering.