ObjectiveTo study the ectopic osteogenesis and biocompatibility of bone morphogenetic protein 2 (BMP-2)-derived peptide P24 loaded chitosan-4-thio-butylamidine (CS-TBA) hydrogel.MethodsFirst, the CS-TBA/hydroxyapatite (HA) solution was prepared by using chitosan, 2-iminothiolane hydrochloride, and HA. Then, the different amount of P24 peptides were added to the CS-TBA/HA to prepare the CS-TBA/5%P24/HA and CS-TBA/10%P24/HA solutions. Finally, β-glycerophosphate disodium (β-GP) was added to the CS-TBA/HA, CS-TBA/5%P24/HA, and CS-TBA/10%P24/HA to prepare the CS-TBA/HA/β-GP, CS-TBA/5%P24/HA/β-GP, and CS-TBA/10%P24/HA/β-GP hydrogels, respectively. Eighteen Sprague Dawley female rats were randomly divided into 3 groups (n=6), which were injected into the back muscle pouches with equal volume CS-TBA/HA/β-GP hydrogel (group A), CS-TBA/5%P24/HA/β-GP hydrogel (group B), and CS-TBA/10%P24/HA/β-GP hydrogel (group C). The animals were sacrificed at 4 and 8 weeks and conducted micro-CT. The ability of biodegradation and osteogenesis of hydrogl was detected by trabecular thickness (Tb.Th), trabecular number (Tb.N), bone mineral density (BMD), and histological staining (HE and Masson).ResultsAll the rats survived to the time point of the harvest. Micro-CT results showed that the new bones gradually increased in each group after operation. At the same time, the new bone formation was more obvious in groups B and C than in group A, and with the increase of P24 concentration, new bone formation in group C was much more than that in group B. The Tb.Th, Tb.N, and BMD increased gradually in 3 groups, and the differences between 4 and 8 weeks were significant (P<0.05) except the Tb.Th in group A. At different time points, the Tb.Th, Tb.N, and BMD were significantly higher in groups B and C than in group A (P<0.05), and in group C was higher than in group B (P<0.05), showing significant differences between groups. Histological staining showed that the materials of groups B and C were biodegradable, and the osteogenic effect was increased with the increase of P24 concentration.ConclusionP24 peptide can improve the ectopic osteogenesis of CS-TBA hydrogel, and the 10% concentration is more effective.
OBJECTIVE: To establish the animal models of mandibular distraction osteogenesis in rabbits and study its osteogenetic mechanism. METHODS: The right mandibles just anterior to the first molars of 12 rabbits were performed osteotomies, and the mandibles were positioned with distractors. The left mandibles were control group without operation. After 1 week, the distractors were stretched 0.9 mm every day for 10 days progressively. One day, 2, 4, 8 weeks after distraction, the mandibles were studied with gross measurement, X-ray, and histological examination. RESULTS: The right mandible were lengthened 8.3 mm on average without bone nonunion and deformity healing. It was observed that the gaps between the distracted bone edges were first occupied by fibrous tissue. Two weeks after distraction, it was found that the gaps were bridged by callus in X-ray, the new bone and the normal bone could not be differentiated clearly after 8 weeks. In histological sections, there were collagen bundles in early distraction, then those collagen bundles were calcificated and become trabeculaes. No Cartilage was found during distraction. CONCLUSION: It suggests that the rabbit mandible can be lengthened by distraction osteogenesis, and the new bone is formed by intramembranous ossification.
Objective
To summarize the recent progress of cell-based approaches for promoting bone regeneration in distraction osteogenesis (DO).
Methods
Recent literature concerning enhancement of bone regeneration following DO using cell-based approaches was reviewed and analyzed.
Results
An overview of 4 different cell-based approaches was mainly provided: single cell injection, cell scaffold-based strategies/injectable tissue engineered bone, microtissue technology or cell aggregate technology, and stem cell gene therapy. Each has its advantages and disadvantages. Other methods are still in the experimental research except that compound injection of bone marrow mesechymal stem cells and platelet-rich plasma has been applied to clinical practice.
Conclusion
The cell-based approach is a promising strategy in the field of bone regenerative medicine. These approaches have bright future in promoting bone regeneration and reducing the treatment period in DO in the clinical application. However, well-designed preclinical studies are required to establish safe and effective guidelines for cell-based approaches to promoting bone regeneration during DO.
Objective To investigate the feasibility and effectiveness of ulnar cortex transverse transport technique in treating upper extremity thromboangiitis obliterans (TAO). MethodsA retrospective analysis was conducted on the clinical data of 7 male patients with upper extremity TAO who were admitted and met the inclusion criteria between January 2019 and July 2022. The patients ranged in age from 32 to 50 years, with a mean age of 40.1 years. The disease duration ranged from 6 to 24 months, averaging 13.6 months. The smoking history ranged from 8 to 31 years, with a mean of 18.4 years. All patients presented with finger ulcers or gangrene, including 1 case affecting the thumb and index finger, 1 case affecting the index and middle fingers, 1 case affecting the middle and ring fingers, 1 case affecting only the ring finger, and 3 cases affecting the ring and little fingers. The preoperative visual analogue scale (VAS) score was 9.1±0.7. All patients underwent treatment with the ulnar cortext transverse transport technique. The wound healing time and the disappearance time of rest pain were recorded. The VAS score was used to assess the degree of hand pain before and after operation. Serum interleukin 6 (IL-6) levels were measured before operation and at 1 month after operation. Computed tomography angiography (CTA) of the affected limb was performed before operation and at 3 months after operation to evaluate changes in blood vessels. The clinical outcomes were evaluated at 1 year after operation based on the Patwa and Krishnan grading system. ResultsAll 7 patients were followed up 12-17 months, with an average of 13.7 months. All patients experienced successful healing of ulcers, with wound healing time ranging from 14 to 21 days, averaging 17.3 days. During the follow-up, no complication occurred, and there was no recurrence of ulcers. The disappearance time of rest pain ranged from 8 to 15 days, averaging 12.1 days. The pre- and post-operative (1-month) serum IL-6 levels were (25.1±5.9) pg/mL and (11.9±2.9) pg/mL, respectively, with a significant difference (t=5.363, P=0.002). CTA examination at 3 months after operation revealed partial revascularization of upper extremity arteries and establishment of collateral circulation, showing significant improvement compared to preoperative status. The VAS scores at 1, 7, 28 days, and 6 months postoperatively were 6.4±0.8, 3.7±0.8, 0.6±0.8, and 0.1±0.4, respectively, all of which significantly improved compared to preoperative scores (P<0.05). Furthermore, the VAS scores gradually decreased over time, with significant differences observed between postoperative time points (P<0.05). At 1 year after operation, the effectiveness of all 7 patients were evaluated as excellent based on the Patwa and Krishnan grading system. ConclusionThe ulnar cortex transverse transport technique can improve blood circulation in the upper limb of patients with TAO, reconstruct microcirculation, inhibit inflammation, promote ulcer healing, and alleviate limb pain.
Objective To examine the mRNA expression of activin A(ACT A) and follistatin(FS) during mandibular lengthening and to elucidate the regulating pattern of during mandibular distractionosteogenesis.Methods Skeletally mature-white New Zealand rabbits were established right mandibular distraction osteogenesis models and the mandibles were lengthened 7 days after osteomy. Atthe end of latency period and the end of distraction period, 10,20, 30, 40 and60 days after fixation, the regenerating tissue of animals’ lengthened mandibles and that of the other side normal mandibles were harvested to extract RNA andto analyse ACT A, FS mRNA by RT-PCR.Results The expression of ACT A mRNA was not detectable in normal bone tissue and ACT A mRNA began to express at the end of latency period. The expression of ACT AmRNA increased gradually along with the beginning of distraction and reached the peak on the 10th and 20th days of distraction which was 5.04 and 4.98 times as much as that of the end of latency period, respectively. The trend of expression of FS mRNA during mandibular distraction osteogenesis was the same as expression of ACT A mRNA. Conclusion ACT A/FS play an important role during rabbit mandibular distraction osteogenesis.
Objective To investigate the mode and influential factor of newbone formation following distraction osteogenesis in mandibular lengthening. Methods Corticotomy was performed on bilateral mandibles in twelve adult male goats. A custommade distractor was used to lengthen the mandible at a rate of 1mm/day for 10 days (total 10 mm elongation). Four goats were sampled respectivelyat 2, 4 and 8 weeks after completion of distraction. The lengthening mandibles were examined by roentgenography and histology. Results Newly formed callus was observed in the distraction gap after mandibular lengthening. The new bone exhibited intramembranous ossification generally, but cartilage islands could be found in the specimen that diastractor loosed. Conclusion The above findings indicate that the mode of new bone formation in mandibular lengthening following distraction osteogenesis appears to be intramembranous ossification and that endochondral ossification takes place in case distractor has loosened.
Objective To investigate the effectiveness of tunnel osteogenesis technique combined with locking plate in the treatment of aseptic non-hypertrophic nonunion of femoral shaft. MethodsThe clinical data of 23 cases of aseptic non-hypertrophic nonunion of femoral shaft treated with tunnel osteogenesis technique combined with locking plate between January 2017 and December 2020 were retrospectively analysed. There were 17 males and 6 females with an average age of 41.4 years (range, 22-72 years). There were 22 cases of closed fracture and 1 case of open fracture. The types of internal fixation at admission included intramedullary nail in 14 cases and steel plate in 9 cases. The number of nonunion operations received in the past was 0 to 1; the duration of nonunion was 6-60 months, with an average of 20.1 months. Among them, there were 17 cases of aseptic atrophic nonunion of the femoral shaft and 6 cases of dystrophic nonunion. Twenty-two cases were fixed with 90° double plates and 1 case with lateral single plate. The operation time, theoretical blood loss, hospitalization stay, nonunion healing, and postoperative complications were recorded. Harris hip function score, Lysholm knee function score, lower extremity function scale (LEFS), and short-form 36 health survey scale (SF-36) were used at last follow-up to evaluate hip and knee functions. Visual analogue scale (VAS) score was used to evaluate the relief of pain at 1 day after operation and at last follow-up. ResultsThe average operation time was 190.4 minutes, the average theoretical blood loss was 1 458.4 mL, and the average hospitalization stay was 8.2 days. All the 23 patients were followed up 9-26 months, with an average of 18.2 months. The healing time of nonunion in 22 patients was 3-12 months, with an average of 5.6 months. There were 8 cases of limb pain, 8 cases of claudication, 6 cases of limitation of knee joint movement, and 2 cases of limitation of hip joint movement. At last follow-up, the imaging of 1 patient showed that the nonunion did not heal, accompanied by pain of the affected limb, lameness, and limitation of knee joint movement. At 1 day after operation, the VAS score of 23 patients was 6.5±1.8, the pain degree was good in 7 cases, moderate in 12 cases, and poor in 4 cases; at last follow-up, the VAS score was 0.9±1.3, the pain degree was excellent in 21 cases and good in 2 cases, which were significantly better than those at 1 day after operation (t=12.234, P<0.001; Z=–5.802, P<0.001). At last follow-up, the average Harris hip function score of 22 patients with nonunion healing was 94.8, and the good rate was 100%; Lysholm knee function score averaged 94.0, and the excellent and good rate was 90.9%; LEFS score averaged 74.6; SF-36 physical functioning score averaged 85.0 and the mental health score averaged 83.6. ConclusionTunnel osteogenesis technique combined with locking plate in the treatment of aseptic non-hypertrophic nonunion of femoral shaft has a high healing rate and fewer complications, which can effectively relieve pain and improve lower limb function and quality of patients’ life.
Objective To investigate whether combining use of platelet-rich plasma (PRP) and decalcified bone matrix (DBM) has synergistic action on promoting bone consol idation and heal ing. Methods Forty male New Zealand rabbits (weighing 2.2-2.8 kg) were randomly divided into 4 groups (n=10). The whole blood was extracted from the central aural artery and PRP was prepared with the Landesberg’s method. An 1 cm-defect was made below the tibiofibular joint of the lefttibia through osteotomy. In group A, defect was repaired by distraction osteogenesis (1 cm); in group B, defect was repaired with 0.5 cm DBM and then by distraction osteogenesis (0.5 cm); in group C, defect was repaired by distraction osteogenesis (1 cm) and local injection of 1 mL PRP; in group D, defect was repaired by 0.5 cm DBM combined with 1 mL PRP and then by distraction osteogenesis (0.5 cm). Then lengthening started at 7 days after operation, at a rate of 1 mm/day and 0.5 mm every time for 10 days (groups A and C) or for 5 days (groups B and D). After the lengthening, the consolidation was performed. The X-ray films were taken at 0, 12, 17, 27, and 37 days after operation. At 37 days after operation, the tibial specimens were harvested for Micro-CT scanning, three-dimensional reconstruction and biomechanical test. Results The X-ray films showed that new bone formation in groups B and C was obviously better than that in groups A and D at 37 days. The bone mineral density (BMD), bone mineral content (BMC), and bone volume fraction (BVF) of groups B and C were significantly higher than those of groups A and D (P lt; 0.05); the BMD and BMC of group C were significantly higher than those of group B (P lt; 0.05); the BVF had no significant difference between groups B and C (P gt; 0.05). There was no significant difference in BMD, BMC, and BVF between groups A and D (P gt; 0.05). The trabecula number (Tb.N) of group C was significantly more than that of other groups (P lt; 0.05), and the trabecula spacing (Tb.Sp) of group C was significantly smaller than that of other groups (P lt; 0.05), but no significant differencewas found among other groups (P gt; 0.05). There was no significant difference in the trabecula thickness among 4 groups (P gt; 0.05). The ultimate angular displacement had no significant difference among 4 groups (P gt; 0.05). The maximum torque of groups B and C was significantly higher than that of groups A and D (P lt; 0.05); the maximum torque of group C was significantly higher than that of group B (P lt; 0.05); no significant difference was found between groups A and D (P gt; 0.05). Conclusion In the rabbit bone defect/lengthening model, local injection of PRP can enhance bone consol idation effectively during consol idation phase. In normal distraction rate, DBM can promote bone consol idation during distraction osteogenesis. In the early stage of distraction osteogenesis, combining use of DBM and PRP can not further promote bone consolidation and healing.
Titanium and its alloys have become one of the most widely used implant materials in orthopedics because of their excellent mechanical properties and biocompatibility. Implant-associated infection is the main reason of failure of orthopedic implant surgery. The anti-infection modification of implant surface has received more attention in the field of infection prevention and developed rapidly. This article focuses on the current research status of simple anti-infection surface modifications that make titanium implants possess anti-adhesion, bactericidal activity or antibacterial membrane activity, as well as the research progress of composite functional surface modifications that promote bone integration, osteogenesis or immunomodulatory effects on the basis of anti-infection, so as to provide references for the construction of orthopedic implants with composite functions.
ObjectiveAfter using hyaluronic acid (HA) to modify curcumin (CUR), the effects of calcium phosphate cement (CPC) combined with HA/CUR on the proliferation and osteogenesis of osteoblasts were investigated.MethodsFirst, HA and CUR were esterified and covalently combined to prepare HA/CUR, and the characteristics were observed and the infrared spectrum was tested. Then, HA, CUR, and HA/CUR were mixed with CPC according to 5% (W/W) to prepare HA-CPC, CUR-CPC, and HA/CUR-CPC, respectively. Setting time detection, scanning electron microscope observation, injectable performance test, and compression strength test were conducted; and the CPC was used as a control. Osteoblasts were isolated and cultured from the skull of newborn Sprague Dawley rats, and the 2nd generation cells were cultured with the 4 types of bone cement, respectively. The effects of HA/CUR-CPC on the proliferation and osteogenesis of osteoblasts were estimated by the scanning electron microscopy observation, live/dead cell fluorescence staining, cell counting, osteopontin (OPN) immunofluorescence staining, alkaline phosphatase (ALP) staining,and alizarin red staining.ResultsInfrared spectroscopy test showed that HA and CUR successfully covalently combined. The HA/CUR-CPC group had no significant difference in initial setting time, final setting time, injectable rate, and compressive strength when compared with the other 3 groups (P>0.05); scanning electron microscope observation showed that HA/CUR was scattered on CPC surface. After co-culture of bone cement and osteoblasts, scanning electron microscopy observation showed that the osteoblasts, which had normal morphology and the growth characteristics of osteoblasts, clustered and adhered to HA/CUR-CPC. There was no significant difference in cell survival rate between HA/CUR-CPC group and other groups (P>0.05), and the number of cells significantly increased (P<0.05); the degrees of OPN immunofluorescence staining, ALP staining, and alizarin red staining were stronger than other groups.ConclusionHA/CUR-CPC has good biocompatibility and mechanical properties, which can promote the proliferation and osteogenesis of osteoblasts.
