Xiaoming Wu

Intervertebral Spinal Fusion Using a RP-based PLGA/TCP/bBMP Biomimetic Grafting Material

Three-dimensional highly porous poly(DL-lactic-co-glycolic acid)/tricalcium phosphate (PLGA/TCP) scaffolds were synthesized via a rapid prototyping (RP) technique. Bovine bone morphogenetic protein (bBMP) was loaded into the biopolymer scaffolds (PLGA/TCP/bBMP). Both the PLGA/TCP scaffolds and the PLGA/TCP/bBMP composites were evaluated by scanning electron microscopy. Lumbar intervertebral body fusion at L2~3 and L4~5 levels were performed on 15 goats using one of the following graft materials: RP synthesized PLGA/TCP scaffolds (group A), PLGA/TCP/bBMP composites (group B), and autogenous iliac bone graft (group C). All animals were sacrificed 24 weeks after surgery and the spine fusions evaluated by manual palpation tests, histological analyses, and radiography. In group A, the histological analyses showed that the PLGA/TCP scaffolds were biocompatible and biodegradable; however, no new bone was found. In group B, highly cellular bone marrow between the new trabecular bone was present in the fusion mass. In group C, there was a lesser amount of new bone. Twenty-four weeks after surgery, the fusion rate of lumbar intervertebral body fusion in group A, B, and C was 10% (1/10), 80% (8/10), and 50% (5/10), respectively. The fusion rate was significantly higher in group B compared with groups of A and C (p<0.01). Based on these results, extracted bBMP can be loaded in vitro into RP-based highly porous structural PLGA/TCP scaffolds to fabricate new graft composites that appear to be more effective for intervertebral spinal fusions. This biomimetic artificial grafting material holds promise as a tool for spine surgery.

Posterolateral Spinal Fusion in Rabbits Using a RP-based PLGA/ TCP/Col/BMSCs-OB Biomimetic Grafting Material

Three-dimensional highly porous poly(DL-lactic-co-glycolic acid)/ tricalcium phosphate (PLGA/TCP) scaffolds were fabricated using a rapid prototyping technique (RP). The 3D rhombic lamellar PLGA/TCP carriers (20 mm × 20 mm × 3 mm) subsequently were coated with collagen type I (Col) to produce PLGA/TCP/Col composites. Both the RP-based PLGA/TCP scaffolds and the PLGA/TCP/Col composites were observed by scanning electron microscopy. Forty New Zealand white rabbits were equally randomized into 2 groups (group A and group B) and bilaterally underwent posterolateral intertransverse process arthrodesis at the L4—L5 level using the following graft materials: In group A, PLGA/TCP/Col/BMSCs-OB composites (on the right side, group A1, n = 20) and autogenous iliac bone grafts (on the left side, group A2, n = 20) were used; In group B, PLGA/TCP scaffolds plus fresh autogenous bone marrow (on the right side, group B1, n = 20) and PLGA/TCP scaffolds alone (on the left side, group B2, n = 20) were utilized. In group A1, rabbit bone marrow stromal cells (BMSCs) were isolated and cultured under the osteogenic conditions (BMSCs-OB). Structural PLGA/TCP/Col composites then were efficiently loaded with BMSCs-OB and cultured 5 days to make PLGA/TCP/ Col/BMSCs-OB biomaterials. Rabbits were sacrificed after 12-week follow-up and the spinal fusion were evaluated by a general observation, a manual palpation test, histological analyses and radiography. As a result, RP established PLGA/TCP scaffolds with appropriate biomaterial properties including satisfactory microstructure, inter-connectivity and porosity. Modifications to the structural highly porous PLGA/TCP scaffolds with Col (PLGA/TCP/Col) essentially increased the affinity of the carriers to seeding cells. In group A1, radiological evaluation revealed strong ability of new bone formation and bony fusion in the implanted sites and histological analyses showed highly cellular bone marrow between the newly formed trabecular bone was present in the fusion mass. In group A2, there was a reduced amount of newly formed bone. In group B1, only a few bony fusions were obtained. In group B2, PLGA/TCP scaffolds were biocompatible and biodegradable; whereas, no newly formed bone or bony fusion was found. Twelve weeks after surgery, spinal fusion rates in groups of A1, A2, B1, and B2 were 70.0%(14/20), 45.0%(9/20), 15.8%(3/19), and 0%(0/19), respectively. The rates of fusion were significantly higher in groups of A1 and A2 compared with groups of B1 and B2 (p<0.01), and there was no significant difference of fusion rate between group A1 and group A2 (p>0.05). Therefore, RP-based 3D PLGA/TCP/Col/BMSCs-OB biomaterial holds promise as a bone grafting substitute for spinal fusion. Our attempts may provide a novel method for biofabrication of the bionic construct.

Novel 3D Reconstruction Modeling Contributes to Development of Orthopaedic Surgical Interventions

Radiology plays important roles in orthopaedic surgery. Although various conventional radiological assessments including digital X-rays, magnetic resonance imaging (MRI), computerized tomography (CT) and the three-dimensional (3D) CT reconstruction images have been widely developed and utilized for preoperative assessment and planning, there are limitations. For example, despite the advances in 3D digital reconstruction images, the 3D structure, anatomy and damaged situation are still being inspected in a separate and flat manner (i.e. paper, film, etc.). Therefore the requirement of real 3D models for bone and joint has emerged clinically. In the present study, a CAD based 3D visualization system and a rapid prototyping (RP) technique were used to fabricate 3D physical models of highly difficult fractures and severe deformities in skeleton including severe pelvic/acetabular fractures, comminuted proximal humeral fractures, talar/ankle joint fractures, scoliolosis and progressive deformities in extremity. Applications and benefits of the biomedical visualization-based orthopaedic surgical strategies were elucidated.

Rapid anti-tumor effects of gelatin sponge/nano-β-TCP construct on SKOV-3 human ovarian cancer cells in vitro

Nanosized β-tricalcium phosphate (nano-β-TCP) particles were synthesized and characterized by transmission electron microscopy and X-ray diffraction. A surface coating was used to fabricate a medical absorbable gelatin sponge (GS) with nano-β-TCP biocomposite (GSN). The nano-β-TCP particles were ~150 nm in diameter and GSN was highly porous with pore diameter of ~200 μm. Modification via nano-β-TCP coating endowed the biocomposite with actual inhibitory effects on human ovarian cancer SKOV-3 cells. The systematic in vitro evaluations including ultrastructural observation, MTT assay, cell cycle analysis, apoptosis detection, and assessment of proliferating cell nuclear antigen (PCNA) expression data confirm that rapid internalization of nano-β-TCP, cell growth inhibition, G1/S phase cell cycle arrest, apoptosis, and suppression of PCNA expression play important roles in the rapid anti-tumor effects of GNS on SKOV-3 cells. Currently, in vitro and in vivo research work are in progress, including special anti-neoplastic drug delivery and synergistic effects of GSN and chemotherapeutic agents.

Novel 3D reconstruction and visualization contribute to clinical therapy for complex extremity fractures

It is well known that medical imaging and visualization play important parts in traumatological orthopaedic surgery. Conventional radiological techniques including digital X-rays, computerized tomography (CT) and magnetic resonance imaging (MRI) have been widely used in clinic, but they have limitations. In order to achieve much deeper understandings and even better orthopaedic surgical interventions for complex fracture cases, eligible three-dimensional (3D) bone and joint simulations are desired. In this study, a CAD based 3D digital reconstruction system and a rapid prototyping (RP) technique were used to form 3D visualization and physical models of complex extremity fractures (CEF). Applications of the innovative biomedical simulation techniques and benefits of the 3D visualization and biomodeling in the highly difficult extremity fractures were elucidated.

Multilevel Posterior Lumbar Interlaminar Fusion in Rabbits Using Bovine Bone Protein Extract Delivered by a RP-synthesized 3D Biopolymer Construct

Rapid prototyping (RP)-based highly porous poly(DL-lacticco-glycolic acid)/tricalcium phosphate (PLGA/TCP(RP)) scaffolds were fabricated. PLGA/TCP constructs (PLGA/TCP(TS)) were also made via thermally induced phase separation with solvent casting and by particulate leaching approach. Both scaffolds were loaded with bovine bone protein extract (BBPE). Sixty-four New Zealand white rabbits were randomized into four groups (groups of A, B, C, and D) and unilaterally underwent posterior lumbar interlaminar fusion at L2–L4 level. Spinal fusions were systematically evaluated. In groups of A (PLGA/TCP(RP)/BBPE constructs) and C (autogenous iliac bone grafts), good bone fusions occurred in vivo. Histological analyses indicated that endochondral ossification played an essential role in initiation of bone fusions in group A, whereas in group B (PLGA/TCP(TS)/BBPE constructs), few bone fusions were observed. In group D (PLGA/TCP(RP) scaffolds alone), the scaffolds were biocompatible and biodegradable; however, no newly formed bone mass or bone fusion was found. Twelve weeks after surgery, the fusion was significantly higher in groups of A and C compared with groups B and D ( p50.01). The PLGA/ TCP(RP)/BBPE biomaterials have potential as grafting substitutes for bone healing and spinal fusion.Rapid prototyping (RP)-based highly porous poly(DL-lactic-co-glycolic acid)/tricalcium phosphate (PLGA/TCP(RP)) scaffolds were fabricated. PLGA/TCP constructs (PLGA/TCP(TS)) were also made via thermally induced phase separation with solvent casting and by particulate leaching approach. Both scaffolds were loaded with bovine bone protein extract (BBPE). Sixty-four New Zealand white rabbits were randomized into four groups (groups of A, B, C, and D) and unilaterally underwent posterior lumbar interlaminar fusion at L2—L4 level. Spinal fusions were systematically evaluated. In groups of A (PLGA/TCP (RP)/BBPE constructs) and C (autogenous iliac bone grafts), good bone fusions occurred in vivo. Histological analyses indicated that endochondral ossification played an essential role in initiation of bone fusions in group A, whereas in group B (PLGA/TCP(TS)/BBPE constructs), few bone fusions were observed. In group D (PLGA/TCP(RP) scaffolds alone), the scaffolds were biocompatible and biodegradable; however, no n...

Application of computer-assisted novel 3D reconstruction and simulation in orthopaedic surgical treatment of complex proximal humeral fractures

Computer-assisted biomedical imaging and simulation have played essential roles in orthopaedic surgery. In order to achieve much deeper understandings and even better surgical interventions for complex proximal humeral fractures (CPHF), appropriate three-dimensional (3D) bone and joint simulations are expected. In this study, an advanced computer-aided design (CAD) based 3D digitalized reconstruction technique was used to form vivid 3D visualization and simulation of CPHF. Applications of the novel biomedical reconstruction and simulation technique in the special area of bone and joint surgery were elucidated. The clinical outcome of fracture open reduction and internal fixation (ORIF) was improved. Besides, the advantages including declined duration of operation, amount of bleeding and hospital stay were simultaneously revealed (p≪0.05). In conclusion, our results suggest that computer-assisted novel 3D reconstruction and simulation substantially improved the surgical outcomes of CPHF.

Use of advanced computer-aided biomodels in practical orthopaedic education

Advanced computer-aided biomodels are essential for orthopaedic surgery and its medical education. In the present study, three-dimensional (3D) real size physical models manufactured by rapid prototyping (RP) technology together with high resolution 3D digital reconstruction images under control of CAD were used in clinical orthopedics. Besides, these computer-based modern biomodels were also utilized in the practical orthopaedic education. As a result, optimal preoperative planning for complex fracture cases was worked out and performed clinically. Subsequently, the surgical outcomes were markedly improved and good results in medical education for orthopaedic residents and junior doctors were obtained. Roles of the advanced computer-aided biomodels in orthopaedic surgery and its practical medical education were explored in this study.

Applications of RP-based biomedical simulation in clinical orthopedics and its medical practical education

Computer-assisted modern biomedical measures including digital signal processing, imaging, two-dimensional (2D) and three-dimensional (3D) simulation and navigation have played more and more essential parts in advanced orthopaedic surgical interventions. The aim of this study is to explore the roles of rapid prototyping(RP)-based 3D simulation in clinical orthopaedics and its professional medical education. Patients with complex fractures and severe deformities in skeleton were enrolled in this study. An advanced computer-aided design (CAD) based RP technique were used to fabricate real size 3D physical models of complex cases including highly difficult fractures and severe bone and joint deformities. Outcomes of both surgical intervention for patients and clinical education for orthopaedic residents and junior doctors were studied. As a result, much better understanding and accurately preoperative planning for orthopeadic complex cases were achieved and clinical practical skills of residents and junior surgeons were improved. Therefore, our study suggests that appropriate application of RP-based biomodels in complex cases have definitely beneficial impacts on the accuracy of surgery and positively influence the clinical teaching outcome in orthopaedics.

Application of computer-based RP biomodelling in clinical orthopaedic surgery education

Three-dimensional (3D) biomodels are essential for clinical orthopaedics. In this study, in order to improve the outcomes of orthopaedic surgical intervention and its clinical medical education, an advanced computer-based rapid prototyping (RP) biomodelling technique was used to fabricate 3D real size physical models of complex cases including highly difficult fractures and severe bone and joint deformities. As a result, the RP-produced vivid models made great contributions to achievement of much better understanding and preoperative planning for complex orthopaedic cases. On the other hand, outcomes of clinical medical education for orthopaedic residents and junior doctors were improved.