Jian Liu

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.

Mineral status and mechanical properties of cancellous bone exposed to hydrogen peroxide for various time periods.

Processed cancellous bone has been regarded as one alternative for the treatment of bone defects. In order to avoid immunogenic effects and preserve the natural properties of the bone, the optimal processing method should be determined. To observe the influence of hydrogen peroxide on the mineral status and mechanical properties of cancellous bone for various time periods and find the optimal processing time. Cancellous bone granules from bovine femur condyles were treated with 30% hydrogen dioxide for 0, 12, 24, 36, 48, 60 and 72xa0h separately. The microstructure and mineral content of the granules were evaluated by ash analysis, Micro-CT, scanning electron micrograph and energy dispersive X-ray. The biomechanical properties were analyzed by applying cranial-caudal compression in a materials testing machine. With increasing exposure to hydrogen peroxide, the BMD and BMC of granules gradually decreased, and the Ca/P molar ratios clearly increased (Pxa0<xa00.05). Meanwhile, the mineral content of the granules increased from 48.5 ±xa01.3 to 79.5xa0±xa02.1%. Substantial decreases in the strength of the granules were observed, and after 48xa0h severe decreases were noted. The decrease in strength was also evident after normalizing the parameters to the cross-sectional area. Granules of bovine cancellous bone matrix should be processed by hydrogen peroxide for 12 to 36xa0h to fulfill the basic requirements of a bone tissue engineering scaffold. These granules could potentially be useful during orthopedic operations.

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.

Multi-variety bone bank in China

This is a descriptive report of the establishment and operation of a Chinese bone bank, though not a typical one. While being engaged in collection, processing and storage of allogeneic tissues, the bone bank to which the author belongs concurrently develops and produces new, non-human derived, graft materials. Among others is reconstituted bone xenograft (RBX) which possesses strong osteoinductive capability without evoking immune rejection. Hence, its appellation “multi-variety bone bank,” which was established by Dr. Hu Yunyu in 1990, the first of its kind in China. There are several salient features discriminating this bone bank from others. At this hospital-based non-profit institution, allograft hemi-joints are freshly prepared and distributed deep-frozen, instead of being freeze-dried on an industrialized basis for convenient transportation. The former has much more superior biological and mechanical properties as compared with the latter. However, allogeneic tissues are sometimes in short supply due to limited number of donors and the risk of some potential donors carrying viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). New graft materials, including reconstituted bone xenograft (RBX), were developed that serve as a supplement to allografts. RBX has been successfully used in clinical practice for the management of old fractures, nonunions and bone defects, most notably of contaminated, infected open fractures and osteomyelitis with the use of anti-infective reconstituted bone xenograft (ARBX). Additionally the multi-variety bone bank serves as a training base for educating professional personnel and researchers (postgraduates) in theories and technologies of tissue banking. Up to now, eighteen special technical staff members and approximately sixty senior researchers have been trained at this institution.

Fabrication of a RP-Based Biomimetic Grafting Material for Bone Tissue Engineering

Three-dimensional (3D) highly porous poly (DL-lactic-co-glycolic acid)/tricalcium phosphate (PLGA/TCP) scaffolds were fabricated using a rapid prototyping technique (RP). The biopolymer carriers (4mm×4mm×4mm) subsequently were coated with collagen type I (Col) to produce PLGA/TCP/Col composites and utilized as an extracellular matrix for a cell-based strategy of bone tissue engineering. Autologous bone marrow stromal cells (BMSCs) harvested from New Zealand white rabbits were cultured under an osteogenic condition (BMSCs-OB) followed by seeding into the structural highly porous PLGA/TCP/Col composites (i.e. PLGA/TCP/Col/BMSCs-OB). Scanning electron microscopy observation found that the RP-based scaffolds had appropriate microstructure, controlled interconnectivity and high porosity. Modification of the scaffolds with collagen type I (PLGA/TCP/Col) essentially increased the affinity of the carriers to seeding cells, and PLGA/TCP/Col composites were well biocompatible with BMSCs-OB. The PLGA/TCP/Col/BMSCs-OB constructs were then subcutaneously implanted in the back of rabbits compared to controls with autologous BMSCs suspension and carriers alone. As a result, histological new bone formation was observed only in the experimental group with PLGA/TCP/Col/BMSCs-OB constructs 8 weeks after implantation. In the control group with scaffold alone only biodegradation of the carriers was found. Therefore, these results validate our bio-manufacturing methods for a new bone graft substitute.

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.

Construction of Two-Gene Modified Artificial Bone by Using Recombinant Adenovirus

Large osseous defects are difficult to treat because of deficient blood supply on the defected area. To get sufficient blood supply, we designed to establish the adenovirus simultaneously encoding both VEGF and Ang-1 (pAd-VIA) to accelerate the formation of new vessels in the process of bone defect repair. The construction of the adenovirus was performed according to the method reported by Tong-Chuan HE with a tiny modification. Three kinds of adenoviruses were acquired. They are adenovirus pAd-VIA simultaneously encoding VEGF and Ang-1, adenovirus pAd-VEGF encoding VEGF, and adenovirus pAd-Ang-1 encoding Ang-1. The adenovirus prepared in this study could successfully transfer VEGF and Ang-1 into mesenchymal stem cells(MSCs) with high efficiency. Two-gene modified artificial bone was established by use of these adenovirus. In the end, the two-gene modified artificial bone was proved to have good biocompatibility and biological function. Study reports presented here will pave the way for further exploration of vascularization in the process of large osseous defects repair.

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.