Objective To report the anatomical study and clinical application of the medial sural artery pertorator flaps. Methods The anatomical study involved 12 fresh adult cadaver lower legs, the arteries of which were perfused with suspensions of lead oxide and gelatine. The bifurcation, location, length, diameter and blood territories of the medial sural artery and its perforating vessels were recorded by dissection, angiography and photography. The integument of the leg was dissected and ridiographed. The tendency of the vessels was analyzed, the surface areas of cutaneous territories and perforator zones were measured and calculated with Photoshop and Scion Image. With the aid of anatomic study, a series of five clinical cases was reported, including five free medial sural flaps for ipsilateral hand reconstruction. Results There was at least one perforating vessel in the medial sural areas of the specimen. A mean of 2.1 perforators was noted over the medial gastrocnemius muscle. The perforating vessels from the medial sural artery clustered about 9 to 18 cm from the popliteal crease, 1 to 5 cm from the posterior medial line. Their diameter was (1.03±0.22)mm at the deep fascial level. The average vascular territory on the sural area was (107.5±23.9)cm2, and the average supplying area of single perforator was (58.3±17.0)cm2. All the transferred free flaps taken in the 5 clinical cases survived uneventfully. All the patients were followed-up from 6 months to 12 months. The appearance of flaps and the function of the limbs were satisfied. Conclusion The standard method for the study of perforator flap is the lead oxide-gelatin technique. It is the anatomic basis that there are perforating musculocutaneous vessels on the medial gastrocnemius muscles constantly. The free medial sural perforator flap has the advantage of good appearance. It is the safe and suitable choice in the cases when a medium or small-sized flap is required for resurfacing hand injuries.

Objective To report the anatomical study and clinical application of the vascularized composite fibula perforating osteoseptocutaneous flap. Methods Latex injection studies were performed on 24 adult cadaveric lower limbs. The presence, prevalence, and location of the peronel artery and its perforators in the distal leg were documented. 16 vascularized fibul osteoseptocutaneous flaps were performed for reconstruction of composite soft-tissue defect of limbs. The flap areas ranged from 6 cm×4 cm to 16 cm× 8 cm. Results A mean of 5.3 perforating vessels of the peroneal artery was noted in the specimen. 40.6% of them were muscularcutanous perforators, and the other were septacutanous perforators. The perforating vessels were all located within 3.1 cm from the postlateral fibula. The average diameter was 1.1 mm at the deep fascial level, and the interval of them was 4-8 cm. There were two constant perforators which located about 15-25 cm and 4-7 cm from the lateral maleolar respectively. All of the 16 clinical cases survived uneventfully and the time to union of the graft-host junction site were 3 to 5 months. The appearance of flaps and the function of the limbs were satisfied during 10 to 36 months following up. Conclusion It is the anatomic basis that there are pedorating vessels of the peroneal constantly. The vnscularized compound fibula perforating osteoseptocutaneous flap has the advantage of flexible design. It is the safe and suitable choice in the cases when compound bone and soft tissue defects of the limbs are required for reconstruction.

Objective To reports to anatomy and clinical application of the medialis pedis perforator flap. Methods The origin, course, distribution and out diameter of medial plantar perforators, which were located at the septums between the abductor hallucis muscle and the flexor digitorum brevis, and between the abductor hallucis muscle and the skeleton, were observed on 10 sides adult feet specimens perfused with red latex. 11 free medialis pedis perforator flaps were transferred for soft-tissue defect in hand. The areas of tissue defect ranged from 2 cm x 2 cm - 9 cmx 4 cm. Results The medial plantar artery sends 2 perforators with regular anatomy through the septum between the abductor hallucis muscle and the flexor digitomm bre-vis, and 2 perforators with regular anatomy through the septum between the abductor hallucis muscle and nav-icluar bone and the medial cuneiform bone. These perforators supply the medial plantar flap and medialis pedis flap respectively. All of the 11 cases of free medialis pedis perforator flap survived uneventfully. The flap areas ranged from 2 cm × 3 cm - 11 cm× 5 cm. The appearance and functional results were satisfactory with following up for 6 to 24 months. Conclusion The free medialis pedis perforator flap is a good method in repairing soft-tissue defect in hand.

Some of the recombinant protein therapeutics with short half-life requires high frequent dose or injection, which results in poor patient compliance. This challenge has prompted the development of long-acting recombinant proteins in recent years. Four strategies and methods, including chemical modification, protein engineering, fusion proteins and protein glycosylation are used to modify protein molecule and finally obtain improved pharmacokinetics (PK) properties. This article reviews the four strategies of half-life extension and presents a detailed list of long-acting therapeutics on US, EU and China markets.

When the size of a neurosphere cultured in vitro reaches a certain critical value, a necrotic core will appear inside the neurosphere because of the limitation of oxygen or other nutrients transport from medium to the cells in the neurasphere. Large necrotic core will greatly reduce the expansion of NSCs. The cellular automaton (CA) model is applied in this article to model the growth of NSCs in sphere state. The appearance and enlargement of the necrotic core in a neurosphere is calculated by coupling the CA model with the nutrient diffusion analysis in bioreactors. The calculation results indicate that the culture conditions, such as seeding density, the concentration of nutrients in medium and the mass transfer coefficient between a neurosphere and medium, have some effects on the appearance of the necrotic core. However, the necrotic core mainly depends on the inner diffusion. It will certainly appear if the size of the neurosphere is large enough even the outside mass transfer is in a good condition in bioreactors. Additionally, the appearance of the necrotic core resulting from the shortage of oxygen is earlier than that caused by the limitation of glucose. And the growth of the necrotic core is very fast after its appearance, and the whole neurosphere may become necrotic. The model developed with cellular automaton and mass transfer is a good qualitative representation of NSCs growth in bioreactors.
Bioreactors ; Cell Culture Techniques ; methods ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Computer Simulation ; Models, Biological ; Neurons ; cytology ; Spheroids, Cellular ; Stem Cells ; cytology ; Tissue Engineering ; methods

Objective To investigate the effect of prevascularized tissue-engineered bone graft on regeneration of femoral bone defects in rats.Methods Models of femoral bone defect were created at the bilateral hind limbs of 20 healthy female 10 week-old rats which were divided into 2 even groups randomly (n =10).In group A,conventional tissue-engineered bone grafts were transplanted into the femoral bone defects;in group B,tissue-engineered bone grafts and vascular bundles were implanted into the femoral defects.At 1,4 and 8 weeks after operation,3 rats were sacrificed each time in each group to harvest samples.The remaining one in each group served as a spare animal.Regeneration of bone defects and degradation of scaffolds were assessed by radiologic modality and hematein eosin staining.Results At week 1,the new bone ratio (BV/TV) was 5.47％ ± 1.90％ in group A and 8.49％ ± 1.26％ in group B,showing no significant difference (P ＞ 0.05);at weeks 4 & 8,the BV/TV were 17.54％ ±2.04％ and 39.73％ ± 4.01％ in group A,significantly lower than those in group B (25.32％ ± 2.15％ and 53.22％ ± 2.94％) (P ＜ 0.05).At weeks 1 & 4,the scaffold degradation ratios (RSV/SV) were 97.33％ ± 2.52％ and 80.60％ ±4.00％,showing no significant differences from those in group B (95.67％ ±3.51％ and 75.22％ ±6.20％) (P ＞ 0.05).At week 8,the scaffold degradation ratio in group A (65.46％ ±4.51％) was significantly higher than that in group B (50.19％ ±4.91％) (P ＜ 0.05).At week 8,hematein eosin staining showed better integration of scaffolds with the femur,faster degradation of the interior scaffolds and greater osteogenetic activity in group B.Conclusion Prevascularization of tissue-engineered bone graft may increase new bone volume and scaffold degradation rate,promoting repair of femoral bone defects in rats.

Objective To systematically evaluate the biomechanical recovery of drilled holes in the femur in SD rats.Methods Eighteen female SD rats were randomized into 3 even groups (n =6).Models of 2-mm drilled holes in bilateral femurs were established in groups A and B with 2 holes on each side while no drilling was performed in group C.Samples were harvested in group A at postoperative 4 weeks,in group B at postoperative 8 weeks while at both 4 and 8 weeks in group C.The samples were evaluated in terms of linear elasticity (compression test),viscoelasticity (relaxation and creep tests) and durability (fatigue failure test).Micro-CT scan was performed to measure the bone volume fraction (BV/TV) and bone mineral density (BMD) of new bone.Sirus red staining was performed to measure regeneration of type Ⅰ collagen of new bone.Results The elasticity modulus,maximum load,compression strength and conditional yield limit in groups A were significantly lower than those in group B which were also significantly lower than those in group C (P ＜ 0.05).At 7,200 s,the relaxation (14.56 ±0.69 MPa) and creep variation (11.37％ ± 0.70％) in group A were significantly higher than those in group B (11.06 0.63 MPa and 8.98％ ± 0.40％) which were also significantly higher than those in group C (6.99 ±0.56 MPa and 5.10％ ±0.23％) (P ＜ 0.05).At the constant amplitude loads from 20 N to 200 N,from 20 N to 300 N and from 20 N to 400 N,the recycling numbers in group A (6,044.3 ±879.7,4,093.3 ±628.5 and 1,919.3 ±847.5) were significantly lower than those in group B (10,192.3 ± 1,109.1,6,750.6 ± 818.0 and 3,376.6 ± 671.3) which were also significantly lower than those in group C (28,068.3 ±2,702.6,11,788.3 ± 1,141.6 and 5,296.3 ± 735.0) (P ＜ 0.05).By micro-CT scan,the BVT and BMD in group A were significantly lower than those in group B which were also significantly lower than those in group C (P ＜ 0.05).The sirus red staining showed the type Ⅰ collagen in the bone defect area was completely regenerated in group B.Conclusion Systematic biomechanical measurements may actually detect the characteristics of biomechanical recovery of bone holes in SD rats,enriching the basic research on the bone damage repairing progress.

Breast cancer is the most common cancer in women and one of the deadliest cancers worldwide.According to the distribution of tumor tissue,breast cancer can be divided into invasive and non-invasive forms.The cancer cells in invasive breast cancer pass through the breast and through the immune system or systemic circulation to different parts of the body,forming metastatic breast cancer.Drug resistance and distant metastasis are the main causes of death from breast cancer.Research on breast cancer has attracted extensive attention from researchers.In vitro construction of tumor models by tissue engineering methods is a common tool for studying cancer mechanisms and anticancer drug screening.The tumor microenvironment consists of cancer cells and various types of stromal cells,including fibroblasts,endothelial cells,mesenchymal cells,and immune cells embedded in the extracellular matrix.The extracellular matrix contains fibrin proteins(such as types Ⅰ,Ⅱ,Ⅲ,Ⅳ,Ⅵ,and Ⅹcollagen and elastin)and glycoproteins(such as proteoglycan,laminin,and fibronectin),which are involved in cell signaling and binding of growth factors.The current traditional two-dimensional(2D)tumor models are limited by the growth environment and often cannot accurately reproduce the heterogeneity and complexity of tumor tissues in vivo.Therefore,in recent years,research on three-dimensional(3D)tumor models has gradually increased,especially 3D bioprinting models with high precision and repeatability.Compared with a 2D model,the 3D environment can better simulate the complex extracellular matrix components and structures in the tumor microenvironment.Three-dimensional models are often used as a bridge between 2D cellular level experiments and animal experiments.Acellular matrix,gelatin,sodium alginate,and other natural materials are widely used in the construction of tumor models because of their excellent biocompatibility and non-immune rejection.Here,we review various natural scaffold materials and construction methods involved in 3D tissue-engineered tumor models,as a reference for research in the field of breast cancer.