The chitosan thermosensitive hydrogel is liquid at room temperature but gels rapidly when heated to body temperature. This hydrogel are wildly used for cell encapsulation, drug delivery or tissue-engineered scaffolds. The system can sustain the release of macromolecules over a period of several hours to a few days. However, with low-molecular-weight compounds, the release is generally completed within 24 h. To prepare a functional chitosan thermosensitive hydrogel for slow release both broad-spectrum antibiotic chlorhexidine and growth factor recombined human bone morphogenetic protein-2 (rhBMP-2), The beta-cyclodextrin was used to prepare an inclusion complex with chlorhexidine, and then the latter was incorporated into the chitosan thermosensitive hydrogel system. Simultaneously, rhBMP-2 was added into the hydrogel system. By HAAKE viscosity measuring instrument, we contrasted the viscoelastic properties of system with or without objective factors. And the in vitro release kinetics of chlorhexidine and rhBMP-2 was investigated by HPLC (high performance liquid chromatography) and ELISA (enzyme-linked immunosorbent assay) respectively. The results showed that the addition of chlorhexidine/beta-cyclodextrin inclusion complex to the thermosensitive solution did not change the gelling behavior of the thermosensitive system. Further, the in vitro release profiles demonstrated that the release rate of chlorhexidine and rhBMP-2 from hydrogel became slower, controlled delivery over at least 1 month. By first preparing chlorhexidine/beta-cyclodextrin inclusion complex, and then mixing the IC and rhBMP-2 into the chitosan thermosensitive hydrogel, a functional chitosan thermosensitive hydrogel system with ability of slow release both rhBMP-2 and chlorhexidine is successfully made.
Bone Morphogenetic Protein 2 ; Bone Morphogenetic Proteins ; administration & dosage ; Chitosan ; chemistry ; Chlorhexidine ; administration & dosage ; Delayed-Action Preparations ; chemical synthesis ; Drug Carriers ; chemistry ; Drug Combinations ; Hydrogels ; chemistry ; Recombinant Proteins ; administration & dosage ; Temperature ; Transforming Growth Factor beta ; administration & dosage

Tissue engineering has been applied to various tissues, and particularly significant progress has been made in the areas of skin, cartilage, and bone regeneration. Inclusion of bioactive factors into the synthetic scaffolds has been suggested as one of the possible tissue engineering strategies. The growth factors are polypeptides that transmit signals to modulate cellular activities. They have short half-lives, for example, platelet-derived growth factor (PDGF), isolated from platelets, has a half life of less than 2 minutes when injected intravenously. Extended biological activity and the controlled release of growth factor are achieved by incorporating growth factor into the polymeric device. This review will focus on growth factor delivery for tissue engineering. Particular examples will be given whereby growth factors are delivered from a tissue-engineered device to facilitate wound healing and tissue repair.
Animal ; Biomedical Engineering/methods* ; Bone Morphogenetic Proteins/administration & dosage ; Cytokines/therapeutic use ; Cytokines/administration & dosage* ; Growth Substances/physiology

OBJECTIVETo evaluate the effect of autologous bone marrow mesenchymal stem cells (BMSCs) seeded bio-derived bone materials (BBM) combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) in repairing defect of osteonecrosis of femoral head (ONFH).

METHODSEarly-stage osteonecrosis in the left hip was induced in 36 adult New Zealand white rabbits (provided by the Animal Center of Guangxi Medical University, Nanning, China) after core decompression and delivery of liquid nitrogen into the femoral head. Then the animals were divided into three groups according to the type of implants for bone repair: 12 rabbits with nothing (Group I, the blank control group), 12 with BBM combined with rhBMP-2 (Group II), and 12 with BMSCs-seeded BBM combined with rhBMP-2 (Group III). At 4, 8, and 12 weeks after surgery, X-ray of the femoral head of every 4 rabbits in each group was taken, and then they were killed and the femoral heads were collected at each time point, respectively. Gross observation was made on the femoral heads. After hematoxylin and eosin staining, Lane-sandhu scores of X-ray and bone densitometry were calculated and the histomorphometric measurements were made for the new bone trabeculae.

RESULTSAt 12 weeks after surgery, two femoral heads collapsed in Group I, but none in Group II or Group III. X-ray examination showed that the femoral heads in Group I had defect shadow or collapsed while those in Group II had a low density and those in Group III presented with a normal density. Histologically, the defects of femoral heads were primarily filled with no new bone but fibrous tissues in Group I. In contrast, new bone regeneration and fibrous tissues occurred in Group II and only new bone regeneration occurrd in Group III. Lane-sandhu scores of X-ray, bone mineral density and rate of new bone in trabecular area in Group III were higher significantly than those of the other two groups.

CONCLUSIONSOur findings indicate a superior choice of repairing the experimental defect of ONFH with BMSCs- seeded BBM combined with rhBMP-2.

Animals ; Bone Morphogenetic Protein 2 ; Bone Morphogenetic Proteins ; administration & dosage ; Female ; Femur Head Necrosis ; pathology ; therapy ; Male ; Mesenchymal Stem Cell Transplantation ; methods ; Rabbits ; Recombinant Proteins ; administration & dosage ; Tissue Engineering ; methods ; Transforming Growth Factor beta ; administration & dosage

OBJECTIVETo study the effect of poly D,L-lactic acid (PDLLA) screws with PDLLA-rhBMP compound on bone regeneration in the screw holes and fracture ends of dog mandibles.

METHODSA self-control study was carried out in 4 dogs. PDLLA/rhBMP-2 compound screws were implanted to fix the mental fractures and PDLLA screws were used as control. The samples from mandibles were collected at 4, 8, 12, 16 weeks after implantation and observed by radiography and histology.

RESULTSAll dogs showed a greater degree of bone regeneration around PDLLA/rhBMP-2 screws than PDLLA ones and all fractures were fixed and healed well.

CONCLUSIONThe PDLLA-rhBMP screw has a better effect of inducing osteogenesis than PDLLA screw, and is able to exert a good fixation to fracture.

Animals ; Biocompatible Materials ; administration & dosage ; Bone Morphogenetic Protein 2 ; Bone Morphogenetic Proteins ; administration & dosage ; biosynthesis ; genetics ; Bone Screws ; Dogs ; Fracture Fixation, Internal ; methods ; Fracture Healing ; Lactic Acid ; administration & dosage ; Male ; Mandibular Fractures ; surgery ; Polyesters ; Polymers ; administration & dosage ; Recombinant Proteins ; administration & dosage ; biosynthesis ; genetics ; Transforming Growth Factor beta

The aim of this study was to develop a bioactive membrane for inducing bone regeneration. The membrane was composed of polylactic acid, collagen, recombinant human bone morphogenetic protein-2 (rhBMP-2). The PLA + collagen + rhBMP-2 membrane was fabricated by solvent-casting and cool-drying. The mechanic properties of this compound membrane were tested. The two surfaces of membrane were observed by SEM. Degradability of PLA was evaluated by SEM observation and molecular weight measure in vitro and in vivo. The compound membranes were implanted in rabbit muscles. The samples were obtained when animals were sacrificed at different periods: 2 weeks, 1, 2, 3, 6 months after surgery. The biodegradability and biocompatibility of the membrane were evaluated. The heterotopic bone inducing activity of BMP was identified. The results indicated that the strength at extension to failure of the compound membrane was 36.4MPa at 2.3% strain. The compound membrane was found bearing active factor on its coarse side, which can induce bone regeneration. After implantation in vivo, the membrane maintained the structure for three months and degraded in 6 months. Based on histological analysis, there was no obvious inflammation. Heterotopic bone was induced. We could conclude that the PLA + collagen + rhBMP-2 membrane is an absorbable compound membrane that possesses good biocompatibility, adequate mechanic properties and excellent property of bone induction. It could be applied as an ideal membrane for inducing bone regeneration.
Animals ; Biocompatible Materials ; Biodegradation, Environmental ; Bone Morphogenetic Protein 2 ; Bone Morphogenetic Proteins ; administration & dosage ; pharmacology ; Bone Regeneration ; drug effects ; Collagen ; administration & dosage ; pharmacology ; Guided Tissue Regeneration ; Lactic Acid ; administration & dosage ; pharmacology ; Male ; Membranes, Artificial ; Polyesters ; Polymers ; administration & dosage ; pharmacology ; Rabbits ; Transforming Growth Factor beta ; administration & dosage ; pharmacology

OBJECTIVETo study the effects of rhBMP-2 on bone formation of mandibular distraction osteogenesis in rabbits.

METHODSBilateral mandibular osteotomies were performed in 12 mature rabbits. 5 mg rhBMP-2 with the collagen carrier was implanted in the osteotomy site of one side of the mandibles. Only the collagen sponge was placed in the contra-lateral side as control. The mandibles of 8 rabbits were lengthened by 6mm using a custom-made distractor. At 4 weeks after the end of distraction, all animals were killed and the distracted calluses were harvested and processed for histological, scanning electron microscopic, as well as Ca/P ratio analysis.

RESULTSThe regenerated bone was found in the distraction gap after mandibular lengthening. The mandibular side treated with rhBMP-2 had greater amounts of new bone formation and earlier mineralization than contra-lateral side (non-rhBMP-2 treated).

CONCLUSIONRecombinant human BMP-2 appears to be able to accelerate bone formation of mandibular distraction osteogenesis in rabbits.

Animals ; Bone Morphogenetic Protein 2 ; Bone Morphogenetic Proteins ; administration & dosage ; pharmacology ; Bone Regeneration ; drug effects ; Calcification, Physiologic ; drug effects ; Collagen ; metabolism ; Female ; Male ; Mandible ; diagnostic imaging ; drug effects ; ultrastructure ; Osteogenesis ; Osteogenesis, Distraction ; Rabbits ; Radiography ; Recombinant Proteins ; administration & dosage ; pharmacology ; Transforming Growth Factor beta ; administration & dosage ; pharmacology

PURPOSE: To compare the efficacy and safety of recombinant human bone morphogenetic protein (rhBMP) and iliac crest autograft in the fusion treatment of lumbar spondylolisthesis. METHODS: The studies using randomized controlled trials to compare the rhBMP with iliac crest autograft in the treatment of lumbar spondylolisthesis were retrieved from Embase, Pubmed, ProQuest dissertations & theses (PQDT), China national knowledge infrastructure (CNKI), Chinese Biomedical Database, Wanfang Data, Cochrane Library (from March 1998 to March 2018). Postoperative fusion rate, clinical success rate, postoperative intervertebral height, complications, operation time, blood loss and duration of hospitalization were chosen as the outcome indicators. Methodological quality of the trials was critically assessed, and relevant data were extracted. Statistical software Revman 5.3 was used for data-analysis. RESULTS: Eleven articles were included in the meta-analysis. The results showed that, comparing the efficacy of rhBMP with iliac crest autograft, statistical significance was found in the 24-month fusion rate post operation [95% CI (1.38, 24.70), p = 0.02] and operation time [95% CI (-14.22, -2.08), p = 0.008]. There is not sufficient evidence for statistical differences in the remaining indicators. CONCLUSION The current literature shows rhBMP is a safe and effective grafting material in the treatment of lumbar spondylolisthesis. Further evidence is dependent on the emergence of more randomized controlled trials with higher quality and larger sample sizes in the future.
Autografts ; Bone Morphogenetic Proteins ; administration & dosage ; Databases, Bibliographic ; Humans ; Ilium ; transplantation ; Lumbar Vertebrae ; surgery ; Randomized Controlled Trials as Topic ; Recombinant Proteins ; administration & dosage ; Spinal Fusion ; methods ; Spondylolisthesis ; surgery ; Time Factors ; Treatment Outcome

This research sought to asses the efficacity of a new type of tissue engineering bone developed by PDLLA/ PLA-PEG-PLA and BMP as a kind of bone graft substitute in the rabbit model of mandibular defects; 15 mm x 6 mm bilateral mandibular periosteum bone defects were made surgically in 20 New Zealand adult rabbits. The porous scaffolds impregnated with rhBMP-2 were used for the purpose, and the scaffolds without rhBMP-2 were used as control. The methods adopted in this research were: macroscopy, histomorphologic exam, X-ray exam, SEM micrography, computer-aided analysis and graphics. The experimental group was shown to have an earlier inception of bone forming. New bone formation was seen along the border of the original mandibular bone and in the middle. At 12 weeks after surgery,the defects were almost filled with new bone. In the control group, the defects could not be repaired in its entirety, and there was no new bone in the middle. The porous scaffold is a promising carrier for BMP. This kind of bone graft substitute can serve as an osteoconductive and osteoinductive matrix.
Animals ; Bone Morphogenetic Protein 2 ; administration & dosage ; Bone Substitutes ; metabolism ; Female ; Implants, Experimental ; Lactic Acid ; administration & dosage ; Male ; Mandibular Injuries ; surgery ; Osteogenesis ; Polyesters ; administration & dosage ; Polyethylene Glycols ; administration & dosage ; Polymers ; administration & dosage ; Rabbits ; Recombinant Proteins ; administration & dosage ; Tissue Engineering ; Tissue Scaffolds

OBJECTIVETo investigate the incidence and variation of tunnel enlargement after anterior cruciate ligament (ACL) reconstruction with peroneus longus muscle combined with BMP and allogeneic bone.

METHODSACL reconstructions with peroneus longus muscle combined with BMP and allogeneic bone were performed in 18 patients (18 knees)in the study from March 2007 to July 2009. Among the patients,14 patients were male and 4 patients were female, ranging in age from 21 to 47 years, with an average of 35.5 years. Twelve patients had the injuries in the right knee and 6 patients in the left knee. The CT scans were taken in a consistent manner at the 1st week and the 3rd, 6th, 12th months after surgery to measure tibial and femoral tunnel expansion.

RESULTSTunnel enlargement didn't happen in 18 knees. The average enlargement of 18 cases of femoral tunnel was (1.10 +/- 0.42) mm; and the average enlargement of 18 cases of tibial tunnel was (1.00 +/- 0.51) mm. There was statistical significance of femoral tunnel between the 1st week and the 3rd month after surgery (P < 0.05); and there were no significant difference of the tunnel diameters among the 3rd, 6th, and the 24th months postoperatively (P > 0.05). There was statistical significance of tibial tunnel between the 1st week and the 3rd month after surgery (P < 0.05); there were no significant differences of the tunnel diameters among the 3rd, 6th, and 24th months postoperatively (P > 0.05).

CONCLUSIONAnterior cruciate ligament reconstruction with peroneus longus muscle combined with BMP and allogeneic bone could obviously reduce the incidence of tunnel enlargement. The tunnel diameter obviously increase in 3 months after surgery,and it remains basically unchanged later.

Adult ; Anterior Cruciate Ligament ; surgery ; Bone Morphogenetic Proteins ; administration & dosage ; Bone Transplantation ; Female ; Femur ; pathology ; Humans ; Knee Injuries ; surgery ; Male ; Middle Aged ; Muscle, Skeletal ; surgery ; Postoperative Complications ; pathology ; Reconstructive Surgical Procedures ; adverse effects ; Tibia ; pathology ; Transplantation, Homologous

OBJECTIVE: To investigate the effects of low-dose decitabine on levels of soluble CD44 and GDF11, and hematopoietic function in elderly patients with myelodysplastic syndrome (MDS). METHODS: Ninety-nine patients with senile myelodysplastic syndrome (MDS) admitted to our hospital from October 2015 to October 2017 were divided into group A, B and C according to their treatment, each with 33 cases.The patients in group A were treated with low-dose decitabine, the patients in group B were treated with usual dose of decitabine, and the patients in group C were treated with low-dose decitabine plus G-GSF, cytarabine, and aclarithromycin. The changes of soluble CD44, GDF11 levels and hematopoietic function (sTfR/E) were compared before and after treatment. The clinical remission rate and adverse reaction rate in 3 groups were analyzed. RESULTS: Before treatment, the levels of CD44, GDF11 and sTfR/E were not significantly different between the 3 groups (P＞0.05). After treatment, the levels of CD44 and GDF11 were significantly decreased in these groups, while the serum levels of sTfR/E were significantly increased, and there was no significant difference between the 3 groups (P＞0.05). After treatment, the total effective rates of A, B, and C 3 group were 82.3%, 81.8%, and 78.8%, respectively, without statistically significant difference (P＞0.05). During the treatment, the incidence of non-hemotoxic adverse reactions in group A was 8.8%, significantly lower than that in group B and C (30.3%, 27.3%) (P＜0.05, P＜0.05), the incidence of hemotoxic adverse reactions in group A was 39.4%, significantly lower than that 63.6% and 66.7% in group B and C (P＜0.05, P＜0.05). CONCLUSION Low-dose decitabine alone is effective in treating elderly patients with MDS as compared with conventional dose and combination therapy, moreover can significantly reduce the levels of CD44 and GDF11, improve hematopoietic function and low the adverse reactions. Thereby the low dose of decitabine may be a new choice for clinical treatment of MDS.
Aged ; Antineoplastic Combined Chemotherapy Protocols ; Azacitidine ; Bone Morphogenetic Proteins ; Decitabine ; administration & dosage ; therapeutic use ; Growth Differentiation Factors ; Hematopoietic Stem Cell Transplantation ; Humans ; Hyaluronan Receptors ; Myelodysplastic Syndromes ; drug therapy ; Treatment Outcome