OBJECTIVE: Polylactic acid (PLA) is a biodegradable polymer possessing good biocompatibility and biodegradability, and approved as a biomaterial for in vivo implantation by American Food and Drug Administration (FDA). The role of cytokines in promoting osteogenesis and vascularization for constructing tissue-engineered bones has received increasing attention.But exogenous cytokine has shorter half-life in vivo and can not reach and maintain relatively high local level for bone repair. This article reviews the present researches and analyzes the application prospect of PLA and its derivatives in bone tissue engineering to serve as the carrier for polypeptide and protein medicines with controlled release through its degradation.DATA SOURCES: Related articles published between 1993 and 2004were searched in Medline database with key words of "polylactic acid,bone morphogenetic protein, vascular endothelial growth factor, TGF- beta", limiting the language to English; meanwhile the related medical papers between 1993 and 2004 were also searched in the Chinese Periodical Database, limiting the language to Chinese.STUDY SELECTION: Related researches on PLA and its derivatives for constructing bone tissue-engineering Scaffolds and study of PLA scaffolds carrying cytokines were included with the obsolete literature and repetitive researches eliminated.DATA EXTRACTION: Altogether 96 related literatures on PLA and its derivatives for constructing bone tissue-engineering scaffolds were collected, 23 of which were included in this review.DATA SYNTHESIS: PLA/PLA-polyglycolic acid copolymer is a good biodegradable scaffold for controlled drug release, having the dual functions as scaffolds and sustained-release drug carrier. PLA is the earliest scaffold material in bone and cartilage tissue-engineering, and also the most widely used tissue-engineering material at present. BMP is the most frequently adopted cytokine in bone tissue-engineering, and PLA scaffolds carrying sustained-release BMP is studies most thoroughly, but researches on PLA scaffolds carrying vascular endothelia growth factor has not been conducted.CONCLUSION: Development and application of PLA scaffolds carrying various sustained-release cytokines has become the new interest in bone tissue-engineering researches.

ObjectiveTo discuss the clinic application and surgical technique of the free flap by inverted-Y-shape microvascular anastomosis in tissue defect repair and functional reconstruction of the limb.Methods Twenty-two flaps in 18 patients were involved in the study between June 2006 and September 2010( 12 cases for soft tissue defect repair with exposure of the tendons, bones or joints, and 6 cases for functional reconstruction;five cases were around the elbows and 13 cases were around the extremity of the lower limb). Before free flap graft, twelve cases with infective tissue defect were debrided extensively and covered with vacuum sealing drainage from 1 to 2 times and each time last 5 to 7 days until the granulation tissue growing well.Designed the free anterolateral thigh flaps with the transverse and descending branches of the lateral femoral circumflex vessels or free latissimus dorsi flaps with the subscapular and circumflex scapular vessels forming a inverted-Y-shape pedicle to repair the tissue defect or to reconstruct the limb function.The recipient artery was sectioned and the arterial tree of the flap was anastomosed to the recipient vessel by two end-to-end anastomoses.This inverted-Y-shape microvascular anastomosis could supply blood for both the free flap and the extremity of the limb.Not all of the veins of the recipient limb need to be cut off.Observed the circulation of the limb extremity, and evaluated the quality of flaps'survival.ResultsComplete flap survival was achieved in 21 flaps and without vaso-occlusive crisis;while partial flap loss in 1 case, which healed after changing dressings.The mean follow-up was 16.2 (6-36) months postoperatively,appearance of the flaps and the functions of limbs were satisfactory,and no obvious complication was found in the donor site.ConclusionThe free flap by inverted-Y-shape microvascular anastomosis is a new choice for the tissue defect repair and functional reconstruction of the limb,especially for the wound around elbow or extremity of the lower limb with one major artery destroyed.

Objective To investigate the effect of a kind of tissue engineered bone implants on healing of segmental bone defects. Methods A 15 mm bone defect experimental model at the right radius of New Zealand white rabbit was made. 24 animals of this model were divided into three groups at random. PLGA scaffords loaded with 5 mg BMP and about 1?106 BMSCs were implanted in Group 1(n=10); PLGA scaffords loaded with 2.5 mg BMP and about 1?106 BMSCs were implanted in Group 2(n=7); PLGA scaffords loaded with 1 mg BMP and about 1?106 BMSCs were implanted in Group 3(n=7). The osteogenesis at the defect area was observed by regular roentgenography and X-ray analysis, histological changes at the bone defects at 4th, 8th, 12th weeks after operation were studied and the new bone formation was measured by image analysis. Biomechanical analysis was done 12 weeks after operation. Results A large quantity of callus was found in all the 3 groups 4 weeks after repair. At the 12th week, the complete bone healing rate was 7/8, 3/5, 3/5, respectively in Group 1, 2 and 3. Group 1 had the largest quantity of new bone measured by histopathological study and X-ray analysis, and at the 12th week, the medullary cavity in this group became united. The compress stiffness, torsion stiffness and the maximal load in Group 1 were better than those in other groups. Conclusion The tissue engineered bone contructed by PLGA scaffords that are loaded with 5 mg BMP and BMSCs is capable of repairing segmental bone defects.

BACKGROUND:The poly-lactic acid and its ramifications have many advantages, such as eligible biocompatibility,nontoxicity of degradation product, easy procession and suitable intensity. Thus, they have been widely used in bone tissue engineering.OBJECTIVE: To study the cellular biocompatibility and in vitro adhesion of poly(lactic-co-glycolic acid) (PLGA) scaffold and bone marrow stromal stem cells (BMSCs) so as to provide a basis for preparation a PLGA scaffold that can load many cytokines.DESIGN: Contrast observation.SETTING: Department of Orthopaedics and Traumatology in Nanfang Hospital of Southern Medical University.MATERIALS: The experiment was carried out in Key Laboratory of Tissue Construction and Detection of Guangdong Province from September 2004 to June 2005. One New Zealand healthy male rabbit (2 months old, 1.5-2.0 kg weight)was adopted in this study. Experimental materials: PLGA scaffold was obtained from Institute of Polymer Science in Sun Yat-sen University); beta-tricalcium phosphate (β-TCP) was supplied by AO Company (Switzerland).METHODS: Bone marrow was aspirated from the New Zealand rabbit. Mononuclear cells were harvested using whole bone marrow culturing, then were induced and amplified in the conditional culture medium. BMSCs were inoculated onto the PLGA and β-TCP at a concentration of 1 ×109 L-1, while those in the medium without materials were taken as blank control group. The development of implanted cells and the adhesion between cells and materials were observed with phase contrast microscope and scanning electron microscope. The proliferation and cycle of cells were tested with MTT method and flow cytometry.MATN OUTCOME MEASURES: ①Phase contrast microscope was used to observe the development of cells and the adherence between cells and materials at a fixed time every day. ②Cellular development on days 1, 3, 6 was observed by scanning electron microscope. ③Cellular proliferation was detected by MTT method. ④Alkaline phosphatase (ALP) activity was determined by chemical colorimetry.⑤Flow cytometer test: The effects of PLGA and β-TCP on the cellular cycle, content of DNA and polyploid levels of BMSCs were investigated. The DNA index of the candidate cells was also calculated.RESULTS: ①Phase contrast microscope observation: In the blank control group, cells culture for 7-10 days presented a larger number of shuttle-shaped, and no contact inhibition effect was observed. The time of cells beginning adherence in PLGA group was obviously later than that in β-TCP group. Cells began to develop on the circumambience and surface of the materials, with the prolonging of culture time. Most of the cells were multangular. The cells in both PLGA and β-TCP groups were similar to those in control group in items of cellular development and shape. ②Scanning electron microscope observation: On the seventh day of culture, the cells of control group remained a monolayer and amalgamated to be a patch with multangular-shaped ones increasing. There were substances in granule shape on the surface of the cells and micro-silk links between cells. In PLGA group, the cells After 7 days' cultivation proliferated sharply, and the compressed-shaped ones were inosculated to be a patch through integrations among cells, resulting in a large number of matrixes. While in β-TCP group, the number of cells increased from the 7th day. The cells were combined together to be a monolayer and moved to pores with matrixes creating out of cells.③Cellular proliferation: The number of the cells in each group all increased to some extents. However, there was no significant difference between the PLGA group and the control group, as well as the PLGA group and the β-TCP group (P ＞ 0.05).④ALP activity: The　content of ALP in all the groups enhanced without exception, while the activities between the PLGA group and the Both control group, as well as the PLGA group and the β-TCP group had no significant difference (P ＞ 0.05).⑤Cellular cycle:Both PLGA and β-TCP had slight effects on cellular cycle of BMSCs. The cells in each group were all normal diploid,and no heteroploid cells were discovered.CONCLUSION: This type of PLGA scaffold possesses good cellular biocompatibility, and can be used as a carrier of many factors in bone tissue engineering.

Objective To explore the surgical technique and the efficacy of free descending genicular artery perforator flap without saphenous vein for tissue defect. Methods 18 cases of extremity tissue defect were involved in this study from Au?gust 2010 to April 2014, including 16 males and 2 females with an average age of 32.4 years (8 plantar or heel soft tissue defect, 10 back of hand or palm soft tissue defect). 2 old injury cases that had soft tissue defect after scar release were treated by free flaps and the other 16 were open injury with infection, among which 5 cases were combined with fractures or bone defect. Sizes of the skin and soft tissue defect were 2.0 cm × 8.0 cm to 9.0 cm × 12.0 cm. All wounds were treated by free descending genicular artery perforator flap from the contralateral limb. Medial femoral cutaneous nerve was kept in flaps as far as possible. The projection points of descending genicular artery perforator and saphenous vein were detected by Doppler, then the flaps were cut with reverse approach, and saphenous vein and saphenous nerve were preserved. Results All 18 flaps were survived and all cases were fol?lowed up for 3 to 30 months (average, 10.3 months). The flap sizes varied from 2.5 cm×9.0 cm-9.5 cm×13.0 cm. 2 cases with bone defect were healed 3 months later without infection, and the other 3 cases with fractures were healed 2-3 months after operation. The two point’s discrimination distance was 7.0-12.0 mm on the flap. The disabilities of the arm, shoulder, and hand question?naire score averaged 51, and the mean Japanese Orthopaedic Association's foot rating scale was 70.5. Most patients were satisfied with appearance of the recipient and donor sites, among which 5 cases had skin?graft on the donor sites, and the other 12 cases had small scars on the donor sites. Poor healing was detected in 1 case on the thigh which was healed 3 weeks later. There was no par?esthesia and rash on the donor sites. The mean distance between projection points of descending genicular artery perforator and sa?phenous vein was 3.7 cm. Conclusion Free descending genicular artery perforator flap without saphenous vein is an optimal therapy for the extremity tissue defect, which has the advantage of covert donor site, less invasion, less variation of perforator, and could recover the skin sense of recipient site.

Objective:To investigate the effect of transforming growth factor (TGF- β) signal in muscle fiber itself during inflammation/immunity response on intramuscular inflammation. Methods:Sixteen wild C57BL/6 mice (wild group) and sixteen mice with skeletal muscle-specific deficiency of T βRⅡ (knock-out group) between 4-8 weeks of age were selected for this study. Acute muscle injury in mice was induced by injection of myotoxin cardiotoxin (CTX) into gastrocnemius. The differences in intramuscular inflammation were compared between the wild and knock-out groups on 0, 4, 7 and 10 d after CTX injection by observing exudation of mononuclear phagocytes, macrophages, M1 type macrophages, CD4 +T cells and helpers T cells (Th1, 2&17). Two newborn C57BL/6 wild mice and 2 SM TGF- βr2-/- knock-out mice were selected to culture primary myoblasts in vitro which were divided into 2 groups: an interferon group subjected to interferon simulation and a control group subjected to addition of an equal amount of solvent. The differences in expression of IL-6, IL-10, MCP-1, MIP-1α, H-2K b, H2-Ea, Toll-like receptor (TLR)3 and TLR7 were compared between the interferon and control groups, as well as between the wild and knock-out groups. Results:On 4&7 d after CTX injection, the ratios of mononuclear/macrophage (75.73%±3.62%, 45.27%± 2.32%), macrophages (38.67%±2.76%, 24.87%±2.19%), M1 macrophages (43.21%±0.11%, 30.43%±2.19%), CD4 +T cells (20.13%±1.62%, 5.67%±0.32%) in the muscle tissue from the knock-out mice were significantly higher than those from the wild mice (58.52%±2.43%, 29.21%±2.45%; 20.63%±2.32%, 16.23%±1.25%; 24.98%±0.35%, 14.23%±1.69%; 10.70%±0.43%, 2.50%±0.45%), with a majority of Th1&Th17 ( P<0.05). In vitro results showed that the levels of IL-6, MCP-1, MIP-1α, H-2K b, H2-Ea and TLR3 were significantly upregulated in the interferon group compared with the control group and that such upregulation in the nock-out mice was more significant than in the wild mice ( P<0.05). Conclusions:Endogenous TGF- β signal activation plays a role in the functional recovery after muscle trauma, because it is involved in the regulation of immune behavior of muscle fibers, thus affecting intramuscular inflammation and muscle regeneration.

Objective To evaluate the surgical technique and clinical significance of the therapy for ankle soft tissue defect with 2 different flee perforator flaps.Methods Twenty-five cases of ankle soft tissue defect with exposed bone of the ankle were involved in this study from August 2006 to April 2012.and the wound sizes varied from 4.0 cm × 5.5 cm to 11.0 cm × 23.0 cm.Twenty cases with acrotarsium soft tissue defect were repaired by free anterolateral thigh perforator flap,five cases with pelma soft tissue defect were repaired by free saphenous artery perforator flap.Results All Twenty-five flaps survived.At 3 to 50 months follow-up [on an average of (18.0 ± 0.8) months] postoperatively,appearance of the flaps was satisfactory,with 10 to 22 mm in 2-PD,and the sensation percentage beyond S2+ was 13/20 cases and 5/5 cases at 3 months follow-up,respectively.Conclusion The optimal therapy for the acrotarsium soft tissue defect is the free perforator anterolateral thigh flap,and free saphenous artery perforator flap should be used for pelma soft tissue defect.Avoid secondary orthopaedic surgery,pay more attention to the donor site of the flap.VSD can significantly promoting the survival rates of the free perforator flaps if the soft defects are caused by open injury.

Objective To explore the clinical efficacy of medial iliosciatic plating via the Stoppa approach for complex acetabular fractures involving the posterior column.Methods Between February 2015 and February 2016,a total of 16 complex acetabular facture cases treated by the medial iliosciatic plate via the Stoppa approach were retrospectively analyzed in this study.This approach provided good exposure to a large region of the pelvis and acetabulum including pubis symphysis,pubic ramus,anterior and inner wall of acetabulum,quadrilateral surface,inner surface of posterior column,true pelvic margin,greater sciatic notch and sacroiliac articulation.The anterior and column was reduced and fixed by the anterior column plate and the medial ilioseiatie plate.The screw direction and angle were adjusted according to the intraoperative X-ray.Surgical time,amount of bleeding,and relevant complications were recorded.The reduction of the posterior column fracture was evaluated by Matta scoring system on the plain X-ray of the pelvic post-surgery,and functional outcomes of the hip joint affected were evaluated one year post-surgery by the Merle d'Aubigne-Postel scoring system.All the cases were followed for at least 12 months.Results The reduction and fixation of the posterior column was accomplished in all the 1 6 patients.The average surgical time was 165.5 min (range,130-270 min).The average blood loss was 1 245.6 ml (range,600-5 600 ml).Thc intraoperative infusionof concentrated red blood cells averaged 6 units.According to the Matta scoring system,anatomical reduction was achieved in 12 cases,satisfactory reduction in 3,and poor reduction in one.The patients were followed from 12 to 22 months.According to the Merle d'Aubigne-Postel scoring system,there were 11 cases of excellent and 3 cases of good,yielding a good or excellent rate of 87.5％.The average Merle d'Aubigne-Postel score was 15.8 (range,8-18).There were 1 case of external iiiac vein rupture and 1 case of bladder rupture.Both were repaired during surgery.Superior gluteal artery rupture was found in 1 case and surgical ligation of the artery was performed during surgery.Conclusion In the treatment of complicated acetabular fractures involving the posterior column,the medial iliosciatic plating via the Stoppa approach is safe and effective,because it can provide a safe and sufficient operative field for surgeons to reduce and fix the posterior column fractures,and it leads to satisfactory recovery of the patients with limited complications.

Objective To explore the clinical effects of variable angle locking plate ( VLP ) in the treatment of pediatric subtrochanteric femoral fractures. Methods Between January 2012 and November 2014, 9 pre-school children were treated at our department for subtrochanteric femoral fractures. They were 6 boys and 3 girls, with an average age of 4. 8 years ( from 4 to 6 years ) . By the Seinsheimer classification, 5 cases were of typeⅡB and 2 of typeⅡC and 2 of typeⅢA. The intervals between injury and surgery averaged 3 days ( from 2 to 5 days ) . All of them were treated with open reduction and VLP internal fixation. Results All the wounds healed well without any infection. All the stitches were removed within 12 days. They were followed up for 8 to 26 months ( average, 16 months ) . All the fractures united within 3 months after operation. Follow-ups revealed no plate or screw loosening, or refracture at the same site. According to the Beaty imaging criteria, the early outcomes were all satisfactory. At the final follow-ups, all the children gained normal gait after full-weight rehabilitation. The affected and normal hips are nearly identical in range of motion and muscle strength. All the children recovered their pre-injury status. By the Sanders scoring for function of the affected hip, 7 cases were rated as excellent and 2 as good. Conclusion VLP can be an effective option for treatment of subtrochanteric femoral fractures in preschool children patients.

As the descending genicular artery supplies multiple perforating branches around the knee joint,it can be used in corticocancellous,osteomusculocutaneous and other composite tissue flaps to repair composite tissue defects at one stage.Consequently it plays a very important role in the field of reconstruction surgery.At present,however,there has been no systematic review of its clinical applications.Having reviewed all the recent reports available on the free tissue perforator flaps with descending genicular artery,we classified them into five major forms.In this paper,we comment on their anatomical mechanisms,variations and clinical applications.Additionally,we predict that digital technology will be used in the future clinical application of the perforator tissue flaps with descending genicular artery.