Aiming at the problem of scaffold degradation in bone tissue engineering, we studied the feasibility that controlls bone defect repair effect with the inhomogeneous structure of scaffold. The prediction model of bone defect repair which contains governing equations for bone formation and scaffold degradation was constructed on the basis of analyzing the process and main influence factors of bone repair in bone tissue engineering. The process of bone defect repair and bone structure after repairing can be predicted by combining the model with finite element method (FEM). Bone defect repair effects with homogenous and inhomogeneous scaffold were simulated respectively by using the above method. The simulation results illustrated that repair effect could be impacted by scaffold structure obviously and it can also be controlled via the inhomogeneous structure of scaffold with some feasibility.
Oral carcinoma；Platysma myocutaneous flap；Defect repair
Objective To report 4 methods of reconstructing soft tissue defects in oral and maxillofacial regions after tumors resection using cervical pedicle tissue flaps. Methods One hundred seventy-two soft tissue defects were repaired with cervical myocutaneous flaps after resection of oral and facial cancer( 165 cases of squamous cell carcinoma and 7 cases of salivary carcinoma). The clinical stage of the tumors was stage Ⅰ in 21 cases, stage Ⅱ in 116 cases and stage Ⅲin 35 cases. Primary sites of the lesions were the tongue (59 cases), buccal mucosa (55 cases), lower gingiva (26 cases), floor of the mouth (25 cases), parotid gland (4 cases) and oropharynx (3 cases). Infrahyoid myocutaneous flaps were used in 60 cases, platysma flaps in 45 cases, sternocleidomastoid flaps in 59 cases and submental island flaps in 8 cases. The sizes of skin paddle ranged from 2.5 cm×5.0 cm to 5.0 cm ×8.0 cm. Results Among 153 survival flaps, there were55 infrahyoid myocutaneous flaps, 40 platysma flaps, 52 sternocleidomastoid flaps and 6 submental island flaps. There were 11 cases of total flap necrosis and8 cases of partial flap necrosis. The success rates were 91.67%(55/60) for infrahyoid myocutaneous flap, 88.89%(40/45) for platysma flap, 88.14% (52/59) for sternocleidomastoid flap and 75%(6/8) for submental island flap. After a follow-up of 3 11 years(5.7 years on average) among 101 cases local reccurence in 18 cases, cervical reccurence in 4 cases, distance metastasis in 2 cases. The survical rate at 3 years were 83.17%(84/101). Conclusion Cervical pedicle tissue flaps haveclinical value in reconstruction of small and medium-sized soft tissue defects after resection of oral and maxillofacial tumors.
Objective To discuss the role of heparan sulfate (HS) in bone formation and bone remodeling and summarize the research progress in the osteogenic mechanism of HS. Methods The domestic and abroad related literature about HS acting on osteoblast cell line in vitro, HS and HS composite scaffold materials acting on the ani-mal bone defect models, and the effect of HS proteoglycans on bone development were summarized and analyzed. Results Many growth factors involved in fracture healing especially heparin-binding growth factors, such as fibroblast growth factors, bone morphogenetic protein, and transforming growth factor β, are connected noncovalently with long HS chains. HS proteoglycans protect these proteins from protease degradation and are directly involved in the regulation of growth factors signaling and bone cell function. HS can promote the differentiation of stem cells into osteoblasts and enhance the differentiation of osteoblasts. In bone matrix, HS plays a significant role in promoting the formation, maintaining the stability, and accelerating the mineralization. Conclusion The osteogenesis of HS is pronounced. HS is likely to become the clinical treatment measures of fracture nonunion or delayed union, and is expected to provide more choices for bone tissue engineering with identification of its long-term safety.
ObjectiveTo investigate the feasibility of tissue engineered periosteum (TEP) constructed by porcine small intestinal submucosa (SIS) and bone marrow mesenchymal stem cells (BMSCs) of rabbit to repair the large irregular bone defects in allogenic rabbits. MethodsThe BMSCs were cultivated from the bone marrow of New Zealand white rabbits (aged, 2 weeks-1 month). SIS was fabricated by porcine proximal jejunum. The TEP constructed by SIS scaffold and BMSCs was prepared in vitro. Eighteen 6-month-old New Zealand white rabbits whose scapula was incompletely resected to establish one side large irregular bone defects (3 cm×3 cm) model. The bone defects were repaired with TEP (experimental group,n=9) and SIS (control group,n=9), respectively. At 8 weeks after operation, the rabbits were sacrificed, and the implants were harvested. The general condition of the rabbits was observed; X-ray radiography and score according to Lane-Sandhu criteria, and histological examination (HE staining and Masson staining) were performed. ResultsAfter operation, all animals had normal behavior and diet; the incision healed normally. The X-ray results showed new bone formation with normal bone density in the defect area of experimental group; but no bone formation was observed in control group. The X-ray score was 6.67±0.32 in experimental group and was 0.32±0.04 in control group, showing significant difference (t=19.871,P=0.001). The general observation of the specimens showed bone healing at both ends of the defect, and the defect was filled by new bone in experimental group; no new bone formed in the control group. The histological staining showed new bone tissue where there were a lot of new vessels and medullary cavity, and no macrophages or lymphocytes infiltration was observed in the defect area of experimental group; only some connective tissue was found in the control group. ConclusionTEP constructed by porcine SIS and BMSCs of rabbit can form new bone in allogenic rabbit and has the feasibility to repair the large irregular bone defects.
Objective To find out an effective technique torepair large segmental infected bony defect.Methods Calcium phosphate cement(CPC) incorporated with bone morphogenetic protein and gentamycin was embedded in the massive reconstituted bovine xenograft(MRBX), then CPC-MRBX was obtained after CPC’s solidification. In vivo test was applied to test the drug delivery capability of CPC-MRBX, in which it was implanted in the dorsal muscle pouch of 18 rabbits. The drug concentration of animal blood and surrounding soft tissue of the CPC-MRBX in the muscle pouch was measured 1, 2, 5, 10, 15, 20, 25, 30 and 35 d after operation, 2 rabbits each time. Large segmental infected femur defect in the rabbit model was created to test the repairing capability of CPC-MRBX. External fixation was done 1.5~2.0 cm above the knee, the most adjacent nail to fracture site was 0.5～0.8 cm away, and proper pressure was applied to the graft. In experimental group(n=25), the bony defect was replaced by CPC-MRBX, while in the control group(n=15) dissected bone block was re-implanted in original position. The animal was subjected to radiographic, histological examination at 4, 8, 16 and 24 weeks. The general condition was observed after the operation.Results CPC-MRBX was easily made under normal temperature and pressure. In viro drug delivery test showed that the drug concentration of the tissue remainedabove the minimal inhibitory concentration of staphylococcus 30 d after operation and no significant increase of blood drug concentration was observed. In experimental group, no adverse influence was observed. Four weeks after operation, the animal could bear load, bony callus around the graft was observed by X-ray, and abundant chondral tissues that grew into CPC-MRBX were observed by histological method. Eight weeks after operation, progressively increasing bony callus around the graft was observed, external fixation could be removed, normal function was restored, and CPC was degenerated dramatically while new bone tissues were growing. Sixteen weeks after the operation, more new bone tissues grew and CPC was degenerated furtherly while marrow tissues were taking shape. Twenty-four weeks after the operation, femur healed completely and CPC was degenerated completely. In the control group, the autograft remained unhealedon X-ray at 4 weeks, and osteomyelitis manifestation such as inflammatory cells infiltration and osteolysis was detected at 4 weeks. All the animals in the control group died before the 8th week, 4 of which showed positive hemoculture. Conclusion CPC-MRBX is readily available and can be applied to repairing large segmental infected bony defect.30 d after operation and no significant increase of blood drug concentration was observed. In experimental group, no adverse influence was observed. Four weeks after operation, the animal could bear load, bony callus around the graft was observed by X-ray, and abundant chondral tissues that grew into CPCMRBX were observed by histological method. Eight weeks after operation, progressively increasing bony callus around the graft was observed, external fixation could be removed, normal function was restored, and CPC was degenerated dramatically while new bone tissues were growing. Sixteen weeks after the operation, more new bone tissues grew and CPC was degenerated furtherly while marrow tissues were taking shape. Twenty-four weeks after the operation, femur healed completely and CPC was degenerated completely. In the control group, the autograft remained unhealedon X-ray at 4 weeks, and osteomyelitis manifestation such as inflammatory cells infiltration and osteolysis was detected at 4 weeks. All the animals in the control group died before the 8th week, 4 of which showed positive hemoculture.Conclusion CPC-MRBX is readily available and can be applied to repairing large segmental infected bony defect.
【Abstract】 Objective To investigate the effectiveness of the medical calcium sulfate—OsteoSet bone graft substitute in the treatment of defect after excision of jaw cyst. Methods Between December 2009 and May 2010, 15 cases of jaw cystic lesion were treated，including 9 males and 6 females with an average age of 36.6 years (range, 15-75 years). Orthopantomography (OPT) method was used to measure the cyst size before operation, and the size ranged from 1.5 cm × 1.5 cm to 8.0 cm × 3.0 cm. The range of bone defect was from 1.5 cm × 1.5 cm × 1.5 cm to 8.0 cm × 3.0 cm × 3.0 cm after cyst excision intraoperatively. The patients underwent cyst curettage and OsteoSet bone graft substitutes implantation (2-15 mL). Radiological method was used to evaluate the repair effect of OsteoSet pellets. Results The pathology biopsy was periapical cyst in 7 cases, odontogenic keratocyst in 5 cases, and dentigerous cyst in 3 cases. Fifteen patients were followed up 6-12 months. Thirteen patients achieved wound healing by first intention; 2 cases had longer drainage time (5 and 7 days, respectively), the incision healed after the pressure bandage. Swelling occurred in 1 case after 1 month with no symptom of infection. No postoperative infection and rejection was found. The X-ray examination showed that the materials filled the bone defect well after 1 day of operation. OsteoSet bone graft substitutes were absorbed by one-half after 1 month of operation and totally after 3 months by OPT. The low density area was smaller in the original cysts cavity, and high density in the cysts increased significantly with fuzzy boundaries of cysts. At 6 months after operation， there was no obvious difference in image density between the original cavity and normal bone, and the capsule cavity boundary disappeared, and defect area was full of new bone. Conclusion The medical calcium sulfate—OsteoSet bone graft substitute is an ideal filling material for bone defect.
ObjectiveTo explore the feasibility and technical essentials of soft tissue defect reconstruction following malignant tumor removal of limbs using perforator propeller flaps. MethodBetween July 2008 and July 2015, 19 patients with malignant limb tumor underwent defect reconstruction following tumor removal using the perforator propeller flaps. There were 13 males and 6 females with an average age of 53.4 years (range, 20-82 years). The disease duration ranged from 1 to 420 months (mean, 82 months). The tumors located at the thigh in 10 cases, at the leg in 2 cases, at the arm in 1 case, at the forearm in 1 case, around the knee in 2 cases, and around the elbow joint in 3 cases. Totally 23 flaps (from 8 cm×3 cm to 30 cm×13 cm in size) were used to reconstruct defects (from 4 cm×4 cm to 24 cm×16 cm in size). The potential source arteries included the femoral artery (n=2) , profunda femoral artery (n=3) , superficial circumflex iliac artery (n=1) , lateral circumflex femoral artery (n=6) , superior lateral genicular artery (n=2) , peroneal artery (n=2) , anterior tibial artery (n=1) , brachial artery (n=4) , and radial artery (n=1) . The remaining one was a free style perforator flap. ResultsPartial distal flap necrosis occurred in 3 cases after surgery with rotation angles of 180, 150, and 100° respectively, which were reconstructed after debridement using a free-style perforator flap in 1 case and using free skin grafting in the other 2 cases. The other 20 flaps survived completely after surgery. Primary healing of incisions was obtained at the donor and recipient sites. There was no severe complication such as infection, hematoma, and total flap failure. All patients were followed up 3 months to 5 years (mean, 19 months). One patient with malignant melanoma around the elbow joint had tumor recurrence, and underwent secondary tumor resection. The appearance, texture, and color of the flaps were similar to those at the recipient site. ConclusionsFor patients with malignant tumor of the limb, the perforator propeller flap can be an alternative option for soft tissue defect reconstruction after tumor resection, with the advantages of relatively simple operation and remaining the main vessels.
Objective To investigate the role and regulatory mechanism of ring finger protein 11 (RNF11) on Akt signaling pathway in the process of osteogenesis of bone marrow mesenchymal stem cells (BMSCs) to provide ideas for further clarifying its osteogenesis mechanism and its use in clinical treatment in the future. Methods BMSCs were isolated and cultured from fresh bone marrow of healthy donors and subcultured. The 4th generation cells were used in experiments after identification by flow cytometry, and osteogenic, chondrogenic, and adipogenic induction. BMSCs were cultured in osteogenic differentiation medium for 0-14 days. The degree of osteogenic differentiation was detected by Alizarin red staining and alkaline phosphatase (ALP) staining, and the protein expression of RNF11 was detected by Western blot. The 4th generation BMSCs were divided into blank control group (group A), empty lentivirus (Lv-NC) group (group B), and knockdown RNF11 (Lv-ShRNF11) group (group C). Osteogenesis was induced and cultured for 0-14 days. The expression of RNF11 protein was detected by Western blot, the degree of osteogenic differentiation was detected by Alizarin red staining and ALP staining, and the relative mRNA expressions of Runx2, osteocalcin (OCN), and osteopontin (OPN) were detected by real-time fluorescence quantitative PCR (qRT-PCR). The protein relative expressions of Akt, Smad1/5/8, and β-catenin signaling pathway were detected by Western blot, expressed as the ratio before and after phosphorylation. In order to study the effect mechanism of RNF11 on Akt signaling pathway, the 4th generation BMSCs were divided into Lv-NC transfection group (group A1), Lv-ShRNF11 transfection group (group B1), and Lv-ShRNF11 transfection supplemented with Akt signaling pathway activator SC79 group (group C1). The protein relative expressions of RNF11 and Akt signaling pathway were detected by Western blot, the related osteogenesis indexes were detected by Alizarin red staining, ALP staining, and qRT-PCR. ResultsThe flow cytometry, and osteogenic, chondrogenic, adipogenic induction culture identification showed that the isolated and cultured cells were BMSCs. The protein relative expression of RNF11 increased gradually with the extension of osteogenic differentiation time (P<0.05); after knockdown RNF11, Alizarin red and ALP stainings showed that the degree of osteogenic differentiation of BMSCs in group C were significantly lower than those in groups A and B, and qRT-PCR detection showed that the relative expression of Runx2, OCN, and OPN mRNA significantly decreased (P<0.05). The protein relative expressions of RNF11 and Akt signaling pathway significantly increased with the extensions of osteogenic differentiation time (P<0.05). After knockdown RNF11, the protein relative expression of Akt signaling pathway in group C was significantly lower than that in groups A and B (P<0.05), while Smad1/5/8 and β-catenin signaling pathway had no significant effect (P>0.05). Compared with group A1, the protein relative expression of RNF11 in groups B1 and C1 significantly decreased (P<0.05). Compared with groups A1 and C1, the protein relative expression of Akt signaling pathway in group B1 was significantly lower (P<0.05); Alizarin red and ALP stainings showed that the degree of osteogenic differentiation of BMSCs in group C1 were slightly lower than that of group A1 (P>0.05), but significantly higher than that of group B1 (P<0.05); qRT-PCR detection showed that the relative expressions of Runx2, OCN, and OPN mRNA in group C1 were slightly lower than those of group A1 (P>0.05), but were significantly higher than those of group B1 (P<0.05). ConclusionRNF11 promotes the differentiation of BMSCs into osteoblasts by positively regulating the activation level of Akt signaling pathway. RNF11 can be used as a potential target to improve the bone repair efficacy of BMSCs and treat bone metabolic diseases.
ObjectiveTo compare the effectiveness of complex defects repair between using chimeric anterolateral thigh flap and series-wound flaps after resection of oral and maxillofacial cancer. MethodAfter resection of oral and maxillofacial cancer, defect was repaired with chimeric anterolateral thigh flap in 39 patients between January 2011 and July 2014 (chimeric anterolateral thigh flap group); and defect was repaired with series-wound flaps in 35 patients between January 2009 and December 2010 (series-wound flaps group). There was no significant difference in gender, age, duration of disease, tumor type, tumor staging, defect location, and defect area between 2 groups (P>0.05) . The operation time, flap harvesting and microvascular anastomosis time, stomach tube extraction time, and oral feeding time were recorded and compared between 2 groups, and postoperative complications were observed; the effectiveness was evaluated according to clinical efficacy evaluation table of bone and soft tissue defects reconstruction surgery in oral and maxillofacial region. ResultsVascular crisis occurred in 2 cases of chimeric anterolateral thigh flap group, and 4 cases of series-wound flaps group. Partial necrosis appeared at distal end of a series-wound flaps, and oral fistula and infection developed in 3 series-wound flaps. The other flaps and the grafted skin at donor site survived; wounds at recipient site healed by first intention. The operation time, stomach tube extraction time, and oral feeding time of chimeric anterolateral thigh flap group were significantly shorter than those of series-wound flaps group (P<0.05) , while the flap harvesting and microvascular anastomosis time was significantly longer than that of series-wound flaps group (P<0.05) . The patients were followed up 1-5 years (mean, 2.5 years). At 3 months after operation, the appearance, patients' satisfaction, working conditions, oral closure function, chew, language performance, and swallowing scores of the chimeric anterolateral thigh flap group were significantly better than those of the series-wound flaps group (P<0.05) , while there was no significant difference in diet, mouth opening degree, oral cavity holding water test, and occlusion scores between the 2 groups (P>0.05) . ConclusionsUsing chimeric anterolateral thigh flap for defect repair after resection of oral and maxillofacial cancer can significantly shorten the operation time, accelerate postoperative rehabilitation, and help the functional recovery of oral closure, chewing, language performance, swallowing function when compared with the series-wound flaps.