Giant cell tumor of axial vertebra: surgical experience of five cases and a review of the literature.

BACKGROUND: Due to the complex anatomy of the upper cervical spinal column region and the variable aggressiveness of giant cell tumors (GCTs), there exists no standard treatment for GCTs of axial vertebra. To the best of our knowledge, there are only a few case reports in the literature and no large sum numbers of clinical trials about the treatment of, or research into, axial vertebra GCTs. METHODS: Between 2009 and 2013, five patients pathologically diagnosed with axial vertebra GCTs were treated at our hospital. We performed intralesional excision and odontoid process reconstructive surgery to preserve the odontoid process, followed with adjuvant radiation therapy after surgery. RESULTS: For those with an intact bone shell, part of the ß-TCP (beta tricalcium phosphate) artificial bone could be seen clearly after surgery and became blurred three months after surgery, as seen on a radiograph. One year later, the part of ß-TCP artificial bone was fused as a block. Subsequently, autogenous bone regenerated successfully and artificial bone degraded thoroughly. For those with a defective cortical bone, partial fusion of the odontoid process, autograft ilium and third vertebra body could be seen three months after surgery, and complete fusion was seen nine months later. The odontoid process was preserved successfully, and the upper cervical spine was reconstructed effectively, without implant failure or infection. CONCLUSIONS: In this study, the odontoid process and function of upper cervical vertebra was preserved successfully through lesion curettage, combined with reconstruction with bone grafting, and adjuvant radiation therapy after surgery. During the follow-up periods, no recurrence or complications was observed.

Comparison of chondral defects repair with in vitro and in vivo differentiated mesenchymal stem cells.

The purpose of this study was to compare chondral defects repair with in vitro and in vivo differentiated mesenchymal stem cells (MSCs). A novel PLGA-gelatin/chondroitin/hyaluronate (PLGA-GCH) hybrid scaffold with transforming growth factor-beta1 (TGF-beta1)-impregnated microspheres (MS-TGF) was fabricated to mimic the extracellular matrix. MS-TGF showed an initial burst release (22.5%) and a subsequent moderate one that achieved 85.1% on day 21. MSCs seeded on PLGA-GCH/MS-TGF or PLGA-GCH were incubated in vitro and showed that PLGA-GCH/MS-TGF significantly augmented proliferation of MSCs and glycosaminoglycan synthesis compared with PLGA-GCH. Then MSCs seeded on PLGA-GCH/MS-TGF were implanted and differentiated in vivo to repair chondral defect on the right knee of rabbit (in vivo differentiation repair group), while the contralateral defect was repaired with in vitro differentiated MSCs seeded on PLGA-GCH (in vitro differentiation repair group). The histology observation demonstrated that in vivo differentiation repair showed better chondrocyte morphology, integration, and subchondral bone formation compared with in vitro differentiation repair 12 and 24 weeks postoperatively, although there was no significant difference after 6 weeks. The histology grading score comparison also demonstrated the same results. The present study implies that in vivo differentiation induced by PLGA-GCH/MS-TGF and the host microenviroment could keep chondral phenotype and enhance repair. It might serve as another way to induce and expand seed cells in cartilage tissue engineering.

Treatment of contaminated bone defects with clindamycin-reconstituted bone xenograft-composites.

Contaminated or infected bone defects and osteomyelitis after trauma are frequently encountered in clinical practice. It is difficult to make a successful bone graft and control infection at the same time. To find a better method to resolve this dilemma, we prepared a novel clindamycin-reconstituted bone xenograft-composite (C-RBX-C) that comprised of crude bBMP (bovine bone morphogenetic protein), clindamycin, and cancellous bone scaffold, and investigated the morphology, biocompatibility, antibiotic release profile and osteoinductive potential of this composite. The ultrastructure of C-RBX-C was evaluated by scanning electron microscopy; the biocompatibility and osteoinductive potential were assessed by testing ectopic implants. The antibiotic release profile was evaluated using a disc-diffusion assay. Finally, this composite was used to repair a Staphylococcus aureus contaminated bone defect in a rabbit model. 16 weeks after the implantation of C-RBX-C, the radial defect had been completely recuperated, with significantly better formation of lamellar bone and recanalization of the marrow cavity, than in the controls (scaffolds without clindamycin or bBMP). These results demonstrate that our novel composite, with its concomitant osteoinductive and antibiotic properties, has significant potential for the treatment of contaminated or infected bone defects and osteomyelitis.

Cartilage regeneration using mesenchymal stem cells and a PLGA-gelatin/chondroitin/hyaluronate hybrid scaffold.

The study was to produce a novel hybrid poly-(lactic-co-glycolic acid) (PLGA)-gelatin/chondroitin/hyaluronate (PLGA-GCH) scaffold and evaluate its potentials in cartilage repair. The porous PLGA-GCH scaffold was developed to mimic the natural extra cellular matrix of cartilage. The differentiated mesenchymal stem cells (MSCs) seeded on PLGA-GCH or PLGA scaffold were incubated in vitro and showed that, compared to PLGA scaffold, the PLGA-GCH scaffold significantly augmented the proliferation of MSCs and GAG synthesis. Then autologous differentiated MSCs/PLGA-GCH was implanted to repair full-thickness cartilage defect in rabbit, while MSCs/PLGA for the contra lateral cartilage defect (n=30). Fifteen additional rabbits without treatment for defects were used as control. Histology observation showed the MSCs/PLGA-GCH repair group had better chondrocyte morphology, integration, continuous subchondral bone, and much thicker newly formed cartilage compared with MSCs/PLGA repair group 12 and 24 weeks postoperatively. There was a significant difference in histological grading score between these two groups, which both showed much better repair than control. The present study implied that the hybrid PLGA-GCH scaffold might serve as a new way to keep the differentiation of MSCs for enhancing cartilage repair.

Porous gelatin-chondroitin-hyaluronate tri-copolymer scaffold containing microspheres loaded with TGF-beta1 induces differentiation of mesenchymal stem cells in vivo for enhancing cartilage repair.

The aim of the study was to produce a novel porous gelatin-chondroitin-hyaluronate scaffold in combination with a controlled release of transforming growth factor beta1 (TGF-beta1), which induced the differentiation of mesenchymal stem cells (MSCs) in vivo for enhancing cartilage repair. Gelatin microspheres loaded with TGF-beta1 (MS-TGFbeta1) showed a fast release at the initial phase (37.4%), and the ultimate accumulated release was 83.1% by day 18. The autologous MSCs seeded on MS-TGFbeta1/scaffold were implanted to repair full-thickness cartilage defects in rabbits as in vivo differentiation repair group, while MSCs differentiated in vitro were seeded on scaffold without MS-TGFbeta1 to repair the contra lateral cartilage defects (n = 30). Fifteen additional rabbits without treatment for defects were used as control. Histology observation showed that the in vivo differentiation repair group had better chondrocyte morphology, integration, continuous subchondral bone, and much thicker newly formed cartilage layer when compared to in vitro differentiation repair group 12 and 24 weeks, postoperatively. There was a significant difference in histological grading score between these two experimental groups, and both showed much better repair than that of the control. The present study implied that the novel scaffold with MS-TGFbeta1 might serve as a new way to induce the differentiation of MSCs in vivo to enhance the cartilage repair.

Efficacy of prevascularization for segmental bone defect repair using ß-tricalcium phosphate scaffold in rhesus monkey.

Although small animal model (rabbit) showed successful bone defect repair using prevascularized tissue-engineered bone grafts (TEBG), large animal (rhesus monkey) studies are still needed to extrapolate the findings from animal data to humans. In current study, we investigated the efficacy of prevascularized TEBG for segmental bone defect repair in rhesus monkey. The segmental diaphyseal defects were created in both tibias. In group A, the defect was filled with prevascularized MSCs/scaffold prepared by inserting saphenous vascular bundle into the side groove and a fascia flap coverage; In group B, the defect was filled with MSCs/scaffold with a fascia flap coverage; In group C, the defect was filled with MSCs/scaffold; In group D, the defect was filled with only scaffold. The angiogenesis and new bone formation were compared among groups at 4, 8, and 12 weeks postoperatively. The results showed the prevascularized TEBG in group A could augment new bone formation and capillary vessel in-growth. It had significantly higher values of vascularization and radiographic grading score compared with other groups. In conclusion, the in vivo experiment data of prevascularized TEBG was further enriched from small to large animal model. It implies that prevascularized TEBG has great potentials in clinical applications.

Immobilized lentivirus vector on chondroitin sulfate-hyaluronate acid-silk fibroin hybrid scaffold for tissue-engineered ligament-bone junction.

The lack of a fibrocartilage layer between graft and bone remains the leading cause of graft failure after anterior cruciate ligament (ACL) reconstruction. The objective of this study was to develop a gene-modified silk cable-reinforced chondroitin sulfate-hyaluronate acid-silk fibroin (CHS) hybrid scaffold for reconstructing the fibrocartilage layer. The scaffold was fabricated by lyophilizing the CHS mixture with braided silk cables. The scanning electronic microscopy (SEM) showed that microporous CHS sponges were formed around silk cables. Each end of scaffold was modified with lentiviral-mediated transforming growth factor- ß 3 (TGF- ß 3) gene. The cells on scaffold were transfected by bonded lentivirus. In vitro culture demonstrated that mesenchymal stem cells (MSCs) on scaffolds proliferated vigorously and produced abundant collagen. The transcription levels of cartilage-specific genes also increased with culture time. After 2 weeks, the MSCs were distributed uniformly throughout scaffold. Deposited collagen was also found to increase. The chondral differentiation of MSCs was verified by expressions of collagen II and TGF- ß 3 genes in mRNA and protein level. Histology also confirmed the production of cartilage extracellular matrix (ECM) components. The results demonstrated that gene-modified silk cable-reinforced CHS scaffold was capable of supporting cell proliferation and differentiation to reconstruct the cartilage layer of interface.

Effect of thickness of HA-coating on microporous silk scaffolds using alternate soaking technology.

Hydroxyapatite (HA) can be coated on various materials surface and has the function of osteogenicity. Microporous silk scaffold has excellent biocompatibility. In this study, alternate soaking technology was used to coat HA on microporous silk scaffolds. However, the cell proliferation was found to decrease with the increasing thickness (cycles of soaking) of HA-coating. This study aims to determine the best thickness (cycles of soaking) of HA-coating on microporous silk scaffolds. The SEM observation showed that group with one cycle of alternate soaking (1C-HA) has the most optimal porosity like non-HA-modified microporous silk scaffolds. The proliferation of osteoblasts has no significant difference between noncoated HA (N-HA) and 1C-HA groups, which are both significantly higher than those in two cycles of soaking (2C-HA) and three cycles of soaking (3C-HA) groups. The transcription levels of specific genes (runx2 and osteonectin) in osteoblasts of 1C-HA group were significantly higher than those of N-HA group. Moreover, the levels showed no significant difference among 1C-HA, 2C-HA, and 3C-HA groups. In conclusion, microporous silk scaffold with 1 cycle of HA-coating can combine the biocompatibility of silk and osteogenicity of HA.

Low elastic modulus contributes to the osteointegration of titanium alloy plug.

Resurfacing of cartilage defect with mini titanium plug is considered a promising alternative for the treatment of focal chondral defects. Elastic modulus of the metal implant plays a significant role in force transmission which influences the stability of plug. This study assessed the effects of two kinds of titanium alloy plug with different elastic modulus, that is, titanium 2448 (Ti2448) plug and titanium-6 aluminum-4 vanadium (TAV) plug on osteointegration. The full-thickness chondral defects were created in bilateral knees of dogs and then TAV and Ti2448 plugs were implanted, respectively. After 12 weeks, radiographic evaluation did not reveal any signs of disassembly, subsidence, or periprosthetic radiolucency in both groups. Microcomputed tomography analysis revealed that bone histomorphometric parameters in Ti2448 group were all significantly better than those of TAV group. Furthermore, the value of pullout force in Ti2448 group was also significantly higher. Histology showed that the screw threads of Ti2448 plug were well integrated into the newly formed bone. In contrast, the trabecular bone was sparsely distributed around TAV plug. In conclusion, Ti2448 plug with low elastic modulus showed more favorable characteristics in osteointegration. Ti2448 may be a promising biomaterial for fabricating mini plug applied for cartilage resurfacing.

The analog of Ginkgo biloba extract 761 is a protective factor of cognitive impairment induced by chronic fluorosis.

Ginkgo biloba extract EGb761 is widely used to treat patients with learning and memory impairment in Alzheimer's disease and Parkinson's disease in China. However, it is not yet clear whether the analog of EGb761 (EGb) has a protective effect on the learning and memory damage induced by chronic fluorosis. In this study, 30 Wistar rats were randomly divided into three groups: a control group, a sodium fluoride (NaF) + EGb group, and a NaF group. The rats were administered 0.5 ml water containing NaF (100 mg/l) and EGb (120 mg/kg) per day via gavage. After 3 months, the rats' capacity for learning and memory was tested using a Y-maze. Damage to hippocampal neurons was evaluated by histological examination of the CA3 area. Superoxide dismutase (SOD) activity and the levels of glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were measured. Furthermore, the expression levels of Bcl-2 and Bax and the levels of cleaved Caspase3 in the hippocampus were evaluated by RT-PCR and Western blotting. The results showed that EGb could improve learning and memory abilities, enhance the activities of SOD and GSH-Px, attenuate the level of MDA, upregulate the ratio of Bcl-2/Bax, and downregulate the level of cleaved Caspase3.

Implant failure of Bryan cervical disc due to broken polyurethane sheath: a case report.

STUDY DESIGN: A case report. OBJECTIVE: A rare case of Bryan disc implantation failure due to broken polyurethane sheath was reported. The bone ingrowth at implant-bone interface and wear debris leaking from broken Bryan disc were also observed. SUMMARY OF BACKGROUND DATA: The Bryan disc is one of the most commonly used cervical prostheses and has shown satisfactory results compared with anterior cervical discectomy and fusion in short- and long-term follow-up. The complications, including neurological worsening, heterotopic ossification, kyphosis, and so forth, still occur, although infrequently. The broken polyurethane sheath is an extremely rare complication that has seldom been reported before. METHODS: A 55-year-old female patient experienced progressive neck pain after 8 years of Bryan disc implantation because of cervical spondylotic myelopathy at C5-C6 level. The subsequent magnetic resonance imaging scan demonstrated a cystic mass in front of Bryan disc, with high-signal intensity on T2-weighted images. The Bryan disc was removed and segment (C5-C6) was fused with cage and plate. The bone ingrowth and wear debris of retrieved Bryan disc were studied. RESULTS.: In revision surgery, a cyst with thick pseudocapsule connecting the anterior part of Bryan disc was excised. A transverse crack (5 mm) was identified in the anterior part of polyurethane sheath. The bacteria test of fluid from the cyst showed a negative result. Micro-computed tomography and histological study both indicated abundant bone ingrowth at implant-bone interface. The metal wear debris could be observed around titanium alloy shells. CONCLUSION: This case demonstrates the unique incident of broken Bryan disc after 8 years of implantation. Follow-up imaging shortly after the procedure should be mandatory to monitor such potential complication.

TGF-ß3 immobilized PLGA-gelatin/chondroitin sulfate/hyaluronic acid hybrid scaffold for cartilage regeneration.

Although most in vitro studies indicate that transforming growth factor ß3 (TGF-ß3) immobilized scaffold is suitable for cartilage tissue engineering, in vivo studies of implanting immobilized scaffold for chondral defect repair are still lacking. This study is to evaluate the potentials of TGF-ß3 immobilized poly-(lactic-co-glycolic acid)-gelatin/chondroitin sulfate/hyaluronic acid (PLGA-GCH) hybrid scaffold for cartilage regeneration. The scaffold was fabricated by incorporating GCH micro-sponges into PLGA frameworks and then crosslinked with TGF-ß3 to mimic natural cartilaginous extra cellular matrix (ECM). In vitro study demonstrated that MSCs proliferated vigorously and produced abundant ECM on scaffold. The immunohistochemistry staining and alcian blue staining confirmed the cartilaginous ECM production. The chondrogenic differentiation of MSCs on scaffold was proved by the expression of collagen II gene in mRNA and protein level. Then MSCs/TGF-ß3 immobilized scaffolds were implanted in rabbits for chondral defects repair. After eight weeks, histological observation showed that differentiated MSCs were located in lacunae within the metachromatic staining matrix and exhibited typical chondrocyte morphology. Histological grading scores also indicated the congruent cartilage was regenerated. In conclusion, the TGF-ß3 immobilized PLGA-GCH hybrid scaffold has great potential in constructing the tissue-engineered cartilage.

[Experimental study on gelatin-chondroitin sulfate-sodium hyaluronate tri-copolymer as novel scaffolds for cartilage tissue engineering].

OBJECTIVE: To fabricate a novel gelatin-chondroitin sulfate-sodium hyaluronate tri-copolymer scaffold and to confirm the feasibility of serving as a scaffold for cartilage tissue engineering. METHODS: Different scaffolds was prepared with gelatin-chondroitin sulfate-sodium hyaluronate tri-copolymer by varying the freezing temperatures (-20 degrees C, - 80 degrees C and liquid nitrogen). Pore size, porosity, inter pores and density were observed with light microscopy and scanning electron microscopy (SEM). The load-stiffness curves were compared between different scaffolds and normal cartilage. The number of MSCs attaching to different scaffolds and the function of cells were also detected with MTT colorimetric microassay. RESULTS: The pore size was 300 +/- 45, 230 +/- 30 and 45 +/- 10 microm; the porosity was 81%, 79% and 56%; the density was 9.41+/-0.25, 11.50 +/- 0. 36 and 29.50 +/- 0. 61 microg/mm3 respectively in different scaffolds fabricated at - 20 degrees C, - 80 degrees C and liquid nitrogen; the latter two scaffolds had nearly the same mechanical property with normal cartilage; the cell adhesion rates were 85.0%, 87.5% and 56.3% respectively in different scaffolds and the scaffolds can mildly promote the proliferation of MSCs. CONCLUSION: Gelatin-chondroitin sulfate-sodium hyaluronate tri-copolymer scaffold fabricated at -80 degrees C had proper pore size, porosity and mechanical property. It is a novel potential scaffold for cartilage tissue engineering.