Дисертації з теми "Injectable Cement"

The use of injectable biomaterials is growing as the demands for minimally invasive procedures, and more easily applicable implants become higher, but their availability is still limited due to the difficulties associated to their design. Each year, more than 700,000 vertebral compression fractures (VCF’s) are reported in the US and 500,000 VCF’s in Europe due to primary osteoporosis only. VCF’s can compromise the delicacy of the spinal canal and also cause back pain, which affects the patient’s quality of life. Vertebroplasty was developed in the 80’s, and has proven to be a safe minimally invasive procedure that can, quickly and sustainably, relieve the pain in patients experiencing VCF’s. However, biomaterials for vertebroplasty still have limitations. For instance, ceramic bone cements are difficult to distinguish from the bone using X-ray techniques. On the other hand, acrylic bone cements may cause adjacent vertebral fractures (AVF’s). Large clinical studies have indicated that 12 to 20% vertebroplasty recipients developed subsequent vertebral fractures, and that 41 to 67% of these, were AVF’s. This may be attributed to the load shifting and increased pressure on the adjacent endplates reached after vertebroplasty with stiff cements. The primary aim of this thesis was to develop better injectable biomaterials for spinal applications, particularly, bone cements for vertebroplasty. Water-soluble radiopacifiers were first investigated to enhance the radiopacity of resorbable ceramic cements. Additionally, different strategies to produce materials that mechanically comply with the surrounding tissues (low-modulus bone cements) were investigated. When a suitable low-modulus cement was produced, its performance was evaluated in both bovine bone, and human vertebra ex vivo models. In summary, strontium halides showed potential as water-soluble radiocontrast agents and could be used in resorbable calcium phosphates and other types of resorbable biomaterials. Conversely, linoleic acid-modified (low-modulus) cements appeared to be a promising alternative to currently available high-modulus cements. It was also shown that the influence of the cement properties on the strength and stiffness of a single vertebra depend upon the initial bone volume fraction, and that at low bone volume fractions, the initial mechanical properties of the vertebroplasty cement become more relevant. Finally, it was shown that vertebroplasty with low-modulus cements is biomechanically safe, and could become a recommended minimally invasive therapy in selected cases, especially for patients suffering from vertebral compression fractures due to osteoporosis.

Mestrado em Materiais e Dispositivos Biomédicos
In recent years, the development and innovation of new bone substitutes has revolutionized the lives of millions of patients. The aim of this work is the development and characterization of a bioactive, injectable and ready-to-use system (also called putty or premixed cement) for bone regeneration. The solid phase is constituted by beta-tricalcium phosphate (β-TCP), FastOs® bioglass (FastOs® BG) and monocalcium phosphate monohydrate (MCPM) powders, while the liquid phase comprises glycerol (G). The synthesis of β-TCP powder was obtained by precipitation reactions followed by heat-treatment; FastOs® BG was obtained by melt-quenching. The characterization of the obtained powders was made through X-ray diffraction (XRD) and measurement of the mean particle sizes and particle size distribution. The putty was prepared by mixing the solid and liquid phases and placed in syringes with a screw cap. Regarding clinical application, injectability, setting time (ST) and mechanical strength were investigated to characterize the putty. Structural analyses of the putty were also performed by XRD, Fourier Tranform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). The putty has a solid/liquid weight ratio (S/L) of 3.3, mean ST of ~25 min, ~96% of injectability and a maximum compressive strength of 6 MPa. Therefore, the putty exhibited excellent injectability results, absence of filter pressing effect and acceptable mechanical properties. The structural analysis of the hardened cements revealed the formation of monetite crystals covered by an amorphous apatitic layer after immersion in PBS and water. The results are encouraging and support the conclusion that ready-to-use injectable bone substitutes have excellent handling properties to be used clinically. In accordance with the Directive 93/42/EEC the putty is considered a class III medical device. In order to pave the way towards its commercial release and in order to meet the essential requirements set out in Annex I of the Directive 93/42/EEC, a clinical evaluation has been carried out.
Nos últimos anos, o desenvolvimento e a inovação de novos substitutos ósseos tem revolucionado a vida de milhões de doentes. O objetivo deste trabalho é o desenvolvimento e caracterização de um sistema bioativo, injectável e pronto-a-usar (putty) para regeneração óssea. A fase sólida é constituída por pós de fosfato tricálcico beta (β-TCP), biovidro FastOs (FastOs®BG) e fosfato monocálcico monohidratado (MCPM), enquanto a fase líquida é o glicerol (G). A síntese dos pós de β-TCP foi obtida por reações de precipitação seguida de tratamento térmico; os pós de FastOs®BG foram obtidos por fusão e arrefecimento em água fria (fritagem) (melt-quenching). A caracterização dos pós foi feita por difracção de raios-X (XRD) e medição dos tamanhos de partícula. O sistema injectável pronto-a-usar foi preparado através da mistura das fases sólida e líquida e colocado em seringas seladas com tampa roscada. Do ponto de vista de aplicação clínica, o sistema foi caracterizado tendo em conta a sua injectabilidade, tempo de presa (setting time, ST) e resistência mecânica. A análise estrutural do sistema também foi realizada, através de XRD, espectroscopia de infravermelho com transformada de Fourier (FTIR) e microscopia eletrónica de varrimento (SEM). O sistema injectável pronto-a-usar tem uma razão em peso sólido/líquido (S/L) de 3,3, um ST médio de ~25 min, ~96% de injectabilidade, e 6 MPa de resistência máxima à compressão. Deste modo, o sistema injetável demonstrou excelentes resultados de injectabilidade, tendo-se verificado ainda a ausência do efeito de filter pressing e propriedades mecânicas aceitáveis. A análise estrutural dos cimentos endurecidos revelou a formação de cristais de monetite recobertos por uma camada apatítica amorfa após imersão em PBS e em água. Os resultados obtidos são promissores e permitem concluir que o sistema injetável pronto-a-usar possui excelentes propriedades de manipulação do ponto de vista clínico. De acordo com a Directiva 93/42/CEE o sistema injetável é considerado um dispositivo médico de classe III. Com o objectivo de contribuir para o seu processo de lançamento comercial e seguindo os requisitos essenciais estabelecidos no anexo I da Directiva 93/42/CEE foi elaborado um relatório tendo em conta a avaliação clínica do sistema injectável.

The present work aimed to test in vivo a new biomaterial for vertebral augmentation. Vertebral compression fractures not healing with conservative management are treated through minimally invasive surgical techniques. Presently, most of the cements used in percutaneous bone interventions are based on a polymeric non-resorbable matrix. However, they can present some complications. Calcium suphate-based cements are effective bone substitutes. Disadvantages include their limited shear and compressive strength. To go beyond the state of the art, a new bioactive calcium sulphate-based cement was developed - Spine-Ghost. To test the suitability of the injectable cement for percutaneous vertebroplasty, a preclinical study was mandatory. A new large animal model for percutaneous vertebroplasty was developed in sheep. In the ex vivo model, bone defects were created in the cranial hemivertebrae through a bilateral modified parapedicular approach, and mechanical tests were performed. The ex vivo model is reproducible, and safe under physiological loads. In the in vivo study, two groups of Merino sheep were defined (n=8): a) the control group, injected with a commercial ceramic cement; and b) the experimental group, injected with Spine-Ghost. Of the first interventioned animals, two presented cardiorespiratory distress during the cement injection, and one had mild neurologic deficits in the hindlimbs. All sheep survived and completed the 6-month implantation period. After sacrifice, the samples were assessed by micro-computed tomography, histological, histomorphometric, and immunohistological studies. There was no evidence of cement leakage into the vertebral foramen. No signs of infection or inflammation were observed. Most importantly, there was cement resorption and new trabecular bone formation in the bone defects of all sheep. The model of percutaneous vertebroplasty is considered suitable for preclinical in vivo studies, mimicking clinical application. Spine-Ghost proved to be an adequate material for percutaneous vertebroplasty, with a biological response identical, if not superior, to the one elicited by the available commercial control; Desenvolvimento de modelo animal superior para vertebroplastia percutânea para avaliação in vivo de um novo cimento injetável. Sumário: O trabalho aqui apresentado teve por objetivo a avaliação in vivo de um novo biomaterial injetável para vertebroplastia a cifoplastia percutâneas. As fraturas de compressão vertebral com indicação cirúrgica são tratadas com recurso a técnicas minimamente invasivas. Presentemente, a maioria dos cimentos utilizados baseiam-se numa matriz polimérica não reabsorvível. Podem, no entanto, causar algumas complicações. Os cimentos à base de sulfato de cálcio são substitutos ósseos eficazes, cujas desvantagens incluem resistência limitada a esforços de corte e compressão. Um novo cimento bioativo de sulfato de cálcio - Spine-Ghost - foi desenvolvido. Para testar a sua aplicabilidade na vertebroplastia percutânea, tornou-se imperativo um estudo pré- clínico. Para o efeito, um novo modelo animal para vertebroplastia percutânea foi desenvolvido em ovinos e sujeito a ensaios mecânicos. No modelo ex vivo, foram criados bilateralmente dois defeitos ósseos interligados, nas hemivértebras craniais, através de uma abordagem parapedicular modificada. O modelo ex vivo é reprodutível e seguro sob cargas fisiológicas. No estudo in vivo, definiram-se dois grupos de ovelhas Merino (n=8): a) grupo controlo, injetado com cimento comercial de base cerâmica; b) grupo experimental, injetado com Spine-Ghost. Nos primeiros animais intervencionados, dois apresentaram alterações cardiorrespiratórias durante a injeção de cimento, e um défices neurológicos ligeiros nos membros pélvicos. Todos os animais sobreviveram e completaram o período de implantação de 6 meses. Após a ocisão, as amostras foram avaliadas por microtomografia computorizada, histologia, histomorfometria e imunohistoquímica. Não se observou derrame de cimento para o canal vertebral, nem sinais de infeção ou inflamação. Ademais, verificou-se a reabsorção do cimento e a neoformação de tecido ósseo trabecular no interior dos defeitos ósseos, em todos os animais. O modelo de vertebroplastia percutânea é considerado adequado para estudos pré- clínicos, mimetizando a aplicação clínica. O Spine-Ghost demonstrou ser um biomaterial adequado para vertebroplastia percutânea, com uma resposta biológica idêntica, se não superior, à elicitada pelo controlo comercial.

Le traitement de l'os est un enjeu majeur en vue des difficultés de l'os à se réparer seul. Plusieurs situations chirurgicales exige l'utilisation d'auto- et/ou allogreffes. Le traitement par autogreffe est celui choisi par prédilection pour la reconstruction osseuse, car elle permet la croissance osteoinductive, fournit les cellules osteogéniques et le scaffold osteoconductif. Cependant cette voie présente de nombreuses limitations telles que la morbidité du site donneur, le temps d'opération allongé, l'insufficance en quantité... Il est ainsi nécessaire de développer de nouvelles stratégies thérapeutiques capables d'exploiter le pouvoir naturel régénérant de l'os et d'être délivré de manière moins invasive. Parmi les matériaux étudiés pour le développement de nouveaux scaffolds, les ciments phosphocalciques fournissent de larges avantages concernant les perfomances biologiques : biocompatibilité, ostéoconduction, biorésorption, bioactivité... L'idée de ce projet est de développer et caractériser un nouveau ciment phosphocalcique pour la régénération osseuse. Le but est d'aboutir sur un procédé original pour obtenir un scaffold injectable, chargé en principe actif pour ensuite être délivré localement. L'atout majeur de cette structure est sa similarité avec la composition de l'os et ses propriétés mécaniques
The treatment of bone is a challenge due to the difficulty that has the bone to repair itself. Several surgical situations sometimes require the application of auto- and allografts. Autologous bone grafting is the gold-standard treatment for bone reconstruction as it is the only that can provide osteoinductive growth factors, osteogenic cells and osteoconductive scaffold. These procedures present many limitations including donor site morbidity, increased operative time and providing insufficient quantity or quality. There is therefore a need to develop novel therapeutic strategies able to exploit the natural regenerative potential of bone and that can be delivered in a less invasive manner. Among the materials studied for the development of novel scaffolds, calcium phosphate cements provide many advantages due to its biological performances, including their biocompatibility, osteoconductivity, osteoinductivity, biodegradability, bioactivity, and interactions with cells. The aim of this thesis is the development and characterization of novel calcium phosphate based cements for bone regeneration. Our goal is to develop new original processes for the development of injectable scaffolds. The major advantage of such structures lies in the perfect biocompatibility with the mechanical properties similar to those of bone

Ce travail porte sur la recherche et le développement d'un matériau de substitution osseuse permettant une implantation par chirurgie mini invasive, limitant les infections post-opératoires et dont la résorbabilité serait adaptée à la cinétique de régénération osseuse. Nous nous sommes intéressés à un ciment à base de carbonate et de phosphate de calcium (CaCO3 – CaP) dont la réaction de prise conduit à la formation d'une apatite nanocristalline analogue au minéral osseux. Dans une première partie la cinétique de prise et le produit de réaction ont été caractérisés par différentes techniques, notamment la diffraction des RX et les spectroscopies FTIR et RMN du solide. Un sel d'argent – Ag3PO4 ou AgNO3, choisis pour leurs propriétés antibactériennes – a été ensuite introduit dans la formulation. Son effet sur la cinétique de la réaction chimique de prise a été mis en évidence par traitement des spectres FTIR et RMN et un mécanisme réactionnel original impliquant les ions argent et nitrate dans la formation de l'apatite a été proposé. L'ajout d'un polysaccharide, la carboxyméthylcellulose (CMC), dans la phase solide du ciment a montré une très nette amélioration de l'injectabilité de la pâte, avec la disparition du phénomène de séparation des phases qui limite généralement l'injectabilité des ciments minéraux. La résistance à la compression et le module élastique des ciments composites ont été par ailleurs augmentés, parallèlement à une diminution de leur porosité. Différentes études in vitro en présence de cellules ou de bactéries ont enfin été réalisées et ont mis en évidence respectivement la cytocompatibilité des différentes compositions de ciments étudiées et le caractère antibactérien de ces matériaux à partir d'une certaine concentration en argent. L'implantation in vivo de compositions choisies a présenté des résultats très prometteurs quant à la résorbabilité d'un ciment composite CaCO3 - CaP/CMC/Ag et à la néoformation osseuse
The present work concerns research and development of a material for bone substitution, enabling implantation through a mini-invasive surgery, limiting post-operative infections and whose resorbability is adapted to bone regeneration kinetics. This study focused on a calcium carbonate and phosphate based cement, whose setting reaction leads to the formation of a nanocrystalline apatite, similar to bone mineral. First, the setting kinetics and the reaction products were characterised using different techniques, especially X-ray diffraction and FTIR and solid-state NMR spectroscopies. A silver salt – Ag3PO4 or AgNO3, chosen for their antibacterial properties – was then introduced in the formulation. Its effect on the setting reaction kinetics was revealed by data processing of FTIR and NMR spectra and an original reaction mechanism which involves silver and nitrates in the formation of apatite was proposed. The addition of a polysaccharide, carboxymethylcellulose (CMC), in the solid phase of the cement showed a clear improvement of the injectability of the paste, preventing the occurrence of filter-pressing phenomenon, often limiting the injectability of mineral cements. The resistance to compressive strength and elastic modulus of the composite cement were also improved together with a decrease in their porosity. Different in vitro studies were carried out in the presence of cells or bacteria and demonstrated the cytocompatibility of different cement compositions and their antibacterial properties starting at a certain silver concentration, respectively. In vivo implantation of selected compositions showed promising results concerning resorbability of a composite CaCO3 - CaP/CMC/Ag cement and the associated bone neoformation

Předložená diplomová práce je zaměřená na studium viscoelastického chování kostních past na bázi fosforečnanu vápenatého a vodného roztoku termosenzitivního triblokového kopolymeru, zlepšujícího tokové vlastnosti pasty. V teoretické části je zpracována stručná charakteristika cementů na bázi fosforečnanu vápenatého. Rovněž se zabývá charakteristikou reologických vlastností injektabilních kostních past. Součástí je také stručný přehled aditiv ovlivňujících právě reologické a mechanické vlastnosti past. Experimentální část je zaměřena na charakterizaci triblokového kopolymeru pomocí nukleární magnetické rezonanční spektroskopie a reologie. Dále byly připravovány modifikované fosfátové cementy, u kterých byly posléze studovány viskoelastické vlastnosti. Kostní pasta byla modifikována přídavkem adhezivních sloučenin (dopamin a jodičnan sodný) a antibakteriálním činidlem (selenové nanočástice). Analýza viskoelastických vlastností byla provedena reologickou analýzou, během níž byl primárně sledován proces vytvrzování a tixotropní chování jak nemodifikovaných, tak modifikovaných fosfátových past. Proces vytvrzování probíhal při teplotě 23 °C a 37 °C, imitující fyziologické prostředí. Morfologie fosfátové keramiky byla charakterizována pomocí rastrovací elektronové mikroskopie a velikost částic byla zjištěna pomocí laserového analyzátoru částic. Bylo prokázáno, že výše zmíněná aditiva mají pozitivní vliv na kinetiku procesu vytvrzování kostních past. Selenové nanočástice navíc vylepšily tixotropní chování polymer-fosfátových past. Z tohoto důvodu jsou tyto nové injektabilní kompozitní pasty vhodné pro miniinvazivní chirurgii. Díky aditivům, vykazujících adhezivní vlastnosti, mají potenciál uplatnit se při léčbě zlomenin. Stejně tak se nabízí možnost využít pasty při léčbě osteomyelitidy, a to díky možnému uvolňování antibakteriálních nanočástic.

Injectable biomaterials that are able to set in situ provide clinicians a valuable tool in treating patients with clinically relevant tissue defects, as these can be administered via minimally invasive procedures and able to fill complex-shaped tissue defects. Injectable biomaterials also allow for novel fabrication techniques that aid in developing complex structures that mimic biological tissue. However, clinically-used injectable biomaterials that are currently available possess critical and inherent shortcomings that are difficult to address. The aim of this thesis was to develop and characterize new synthetic injectable biomaterials to address some of these shortcomings. To achieve this aim, the works in this thesis combined two distinct strategies: (1) utilize injectable material platforms not currently established for clinical use, but proven to be biocompatible and exhibit promising properties for filling musculoskeletal tissue defects; and (2) further improve the physicochemical and biological properties of these injectable materials, by incorporating bioactive doped calcium silicate ceramics. In particular, this thesis focused on the development and characterization of three such novel injectable biomaterials: (1) thermoplastic polycaprolactone composited with baghdadite (Ca3ZrSi2O9); (2) strontium-hardystonite (Sr-Ca2ZnSi2O7, Sr-HT)-phosphate cement; and (3) self-setting polyvinyl alcohol hydrogel composited with Sr-HT. All the synthetic injectable materials developed in this thesis possess sets of simultaneous ideal physicochemical and biological properties that address the limitations of injectable biomaterials currently established in the clinical setting. This thesis demonstrates that the physicochemical and biological properties of various injectable material platforms can be improved significantly by incorporating DCSC such as baghdadite and Sr-HT in order to render these materials ideal for filling various musculoskeletal tissue defects.

碩士
國立臺北科技大學
化學工程研究所
102
This study aims to develop an injectable calcium phosphate bone cement injection device directly injected locally and fast curing, can be used as drug delivery adjuvant therapy containing growth factors promote the formation of new bone and improve bone bonding properties to Tetracalcium phosphate (TTCP) and Dicalcium phosphate (DCPA) as a main component formulation design and add hydroxyapatite (HAp) as a seed to accelerate the rate of conversion of anhydrous citric acid, and (CA), the bone can be shortened cement curing time, increase strength, after adding different proportions of methyl cellulose (MC) and polyvinylpyrrolidone (PVP) into calcium phosphate cement binder within, to improve the performance of calcium phosphate bone cement injection, then disodium hydrogen phosphate solution as a binding agent made of composite material. Experimental results show that adding methyl cellulose (MC) and polyvinylpyrrolidone (PVP) adhesives, do basic physical properties, biocompatibility testing and drug controlled release experiments, showing the injection of PVP from MC adhesives and adhesives content increased and decreased, but the MC more, need the more hardened liquid to form a dough-like. Rupture strength increases with the decrease binder content MC, MC no significant effect on the proportion of curing time. Conversely PVP binder added, rupture strength increases with increasing content of PVP binder. And more than 5% PVP binder, bursting strength affect not obvious. Add adhesives for composite materials after immersion test, by observing the microstructure of the specimen surface, you can see the specimen surface will form hydroxyapatite (HAp), cytotoxicity tests are showing toxic materials. Controlled drug delivery system to display material within 24 hours soaking, drug controlled release rate rose to 10 percent; With the increase of immersion time, the subsequent release of the case show a slow rise in the steady state, we can see that the material is suitable as a drug carrier.

碩士
中山醫學大學
口腔生物暨材料科學研究所
97
The aim of this study was to develop novel injectabile calcium silicate-based composite bone cements with drug release for bone repair. The gelatin microspheres containing Chinese herbs were incorporated into calcium silicate powders to form the composite. Moreover, we investigated the effect of the inflammation after adding antibiotics. The drug release, injectability, before and after immersion behavior in physiological solution, including diametral tensile strength, morphology, and phase composition of various cements were evaluated, in addition to biology properties. The results indicated that the gelatin micropaticles may prolong drug release time. The results of injectability show that the pure calcium silicate cement only remained 20% after 5 minutes, however, the composite containing microspheres can extend injection time until 30 minutes. After 20 minutes, the composite containing microspheres can remain 40% injectability. This biocompatibility study indicated the composite containing drug significantly enhanced cell proliferation and differentiation. After Xu-Duan release in the medium could promote cell viability and have 1.35 times higher than the group without drug. Gu-Sui-Bu had about 1.2 times than pure microspheres. Gene expression showed these calcium silicate composites with high osteogenecity. It is concluded that the composite cement are a potential material for bone defect repair.

碩士
國立臺灣大學
醫學工程學研究所
94
Vertebral compression fractures are quite common in worldwide. The most common cause is osteoporosis, which causes bone fragility and predisposes the bone to fractures. Vertebroplasty has been widely adopted to treat vertebral body compression fractures. Vertebroplasty, where bone cement is injected into the weakened vertebrae to stabilize them .Currently, the most commonly used injectable bone cement is poly(methyl methacrylate) (PMMA), but it suffers from the fact that it is not degraded and high curing temperature. Several advantages of PPF has been investigated, including：low crosslinking temperature, biodegradable, injectable . Calcium phosphate cements（CPC）has good biocompatibility and offers the potential for resorption of the cement over time and replacement with new bone .In this study, we want to develop an injectable, biodegradeable bone cement which well be mixed PPF and CPC together. This composite can be used to fill skeletal defects, acting as a mechanical support at the defect site. The purpose of this study was to evaluate the effect of the incorporation of calcium phosphate cement filler on the degradation time, highest crosslinking temperature and compressive strength, respectively. Result show that the highest crosslinking temperature with the absolute values ranging from 38° to 44°C, which was much lower than that of 74°C for poly(methyl methacrylate) bone cement. The value of initial compressive strength was 61.1±3.7 MPa,and the level of compressive strength still in the range of 50~60±10 MPa after 8 weeks. Compare with PMMA, the compressive strength of new bone cement was more similar with native bone tissue. and could lasted over 2 months. Data shown that we have developed degradeable bone cement with well mechanical property and may applied in Vertebroplasty

碩士
國立臺北科技大學
材料科學與工程研究所
97
Rhinoplasty was mainly performed to correct traumatic and improve nasal functionality. Today, it is gaining popularity for esthetic enhancement. A novel technique for rhinoplastry is operated by injecting material into patient’s nasal dorsum or nasal tip and place a removable mold for fixation. It’s a minimally invasive surgical procedure and has advantages of easy to handle, no visible skin incisions, reducing repair time and decreasing patient’s fear. This study is focused on discussing the influences of three different ratios of γ-glutamic acid in CPC on HAP conversion, micro structure, injection, rheology, setting time, degradation and biocompatibility. Results showed the optimum ratio of γ-PGA in CPC for highest HAP conversion, shortest gelation and setting time and 85% clinical acceptable injectability is 1%. The system remains stable after degradable test and the results of cytotoxicity assays showed no harmful to the cell differentiation and proliferation. In summary, this bone cement composite possesses great developing potential to be applied on rhinoplasty and can be a new choice for patients who are afraid of operation.

碩士
國立臺灣大學
醫學工程學研究所
97
Avascular necrosis of the femoral head commonly occurs in the people who are thirty to fifty years old. The most general treatment for early stages of avascular necrosis of the femoral head is core decompression. However, there is no general consensus regarding either the indications for this procedure or the techniques that optimize results. We want to develop a biodegradable and angiogenic bone cement for treatment of avascular necrosis of the hip. Core decompression is followed by injection of bone cement within operation. Bone cement will provide mechanical strength and angiogenic function to increase nutrition supply for bone tissue regeneration. We anticipate the newly formed bone can replace the degraded bone cement and the defect site is able to recovered. Several advantages of poly(propylene fumarate) (PPF) has been investigated, including：biodegradable material and low crosslinking temperature. Calcium phosphate cement (CPC) is bioresorbable and osteoconductive. We combined these two key materials to offer proper mechanical strength for femoral head of patients. By addition of ginsenoside Rg1 which is extracted from panax ginseng as a angiogenic agent, anticipating that this composite can act as a mechanical support at the bone defect site and stimulate bone regeneration simultaneously. The first part of this study is mainly to discuss the influence of three different ratios of CPC to PPF on biocompatibility, mechanical strength, crosslinking temperature and swelling. Results showed bone cement was more biocompatible with increasing the ratio of CPC to PPF. Increasing the ratio of CPC to PPF also strengthened the mechanical strength, reduce the crosslinking temperature and lower swelling effect. In the second part of this study, we chose the optimal ratio of CPC to PPF and mixed them with three different amounts of Rg1. Then the drug release profile was analyzed and the function of released Rg1 was checked. Data revealed the three different ratios of Rg1 to cement shared almost the same pattern in cumulative Rg1 figure. We chose the proper ratio to make extract liquid. Angiogenic function of released Rg1 to human umbilical vein endothelial cell (HUVEC) was tested by tube formation assay within extract liquid. Result showed the released Rg1 was still able to stimulate angiogenesis signficantly. In summary, this bone cement composite possesses great developing potential to be applied on treating avascular necrosis of the femoral head.

Hydroxyapatite (HAp) is a bioceramic particularly suitable for biomedical applications in fields of dentistry and orthopaedics due to its osteoconductivity and biocompatibility, associated with the resemblance of its chemical composition to that of the mineral phase of the human bone. A mesoporous structure increases the bioactivity of hydroxyapatite nanopowders and facilitates the adsorption of drugs. Since the late 80’s, bone cements and pastes have been developed to fill bone defects helping in the regeneration of bone tissue and aiming towards minimally-invasive techniques in the treatment of bone defects. This study aims to produce and study a mesoporous hydroxyapatite (MHAp) cement by mixing MHAp powder, synthesized via sol-gel method, with a liquid solution of hydroxypropylmethylcellulose (HPMC) as a gelling agent. Different concentrations of HPMC and the liquid/solid (L/S) ratio were tested. The MHAp powders produced were analysed using FTIR and XRD to assess their chemical composition and crystalline structure, TEM analysis was made to determine the particle and porous size, and finally, cytotoxicity tests were made to test the powders viability. The MHAp cements were submitted to injectability assays, setting time tests and cytotoxicity tests. All MHAp cements produced are injectable, bioactive and biocompatible. Furthermore, they present setting times which are adequate for the powder and liquid to be mixed and placed into a syringe. Possibility of changing the setting time by changing the liquid solution or the L/S ratio deserves further studies.

碩士
國立臺灣大學
臨床牙醫學研究所
102
Particulated calcium phosphate has become more popular in clinical application in implant-related bone augmentation. The advantages of particulate form of bioceramics is owe to good ostoconductive efficiacy and easily gap filling, however, such particlulated bioceramics is lack of strength in space maintaineance which lead to unpredicated outcome in repair of intraoral large bony defect, such as peri-implant bone defect which heavy occlual loading may be encountered. For this reason, our team try to develop a new injectable bone cement based on α tricalcium phosphate with initial high flowability and subsequent hardness which can be applied intraorally. Furthermore, investigation of functional efficiacy based on canine animal model for such new cement in bone regeneration around large peri-implant defect have also been performed. One Beagle and three Taiwanese hybrid dogs weighing between 7 kg to 10 kg were enrolled in this research protocol. According reseach protocol, the implant with defect can be attributed into four groups, the experimental group (n = 11), bone graft material used is a composite α tricalcium phosphate bone cement with monocalcium citrate; bone graft material in the control group (n = 6) used for the β tricalcium phosphate, hydroxyapatite and type I collagen; blank control group (n = 3) are blank group without graft insertion. The way is to experiment dogs around 4 premolar and the first molar of mandible, after six weeks of wound healing, the present study three groups of different materials and explants arbitrarily assigned according to different points in time, planting mandible in experimental dogs left and right sides, is the first major surgical approach in experimental animals toothless ridge good preparation certain size bone defects , then place the implant placement and bone graft material . There are four time points surgery, namely week 0, 7 weeks, 11 weeks and 15 weeks, the surgery will be performed while the implant resonant frequency and stability Periotest measurement and subcutaneous injected bone dye . Finally, at the sacrificed of the 19 weeks, followed by the use of the implant stability quotient (ISQ) analysis of the stability of the implant Periotest (PTV) analysis, radiographic analysis, tomography analysis, biopsy interpretation , fluorescence labeling was observed with bone analysis , etc. bone around the implant causing bone graft material level of life. Results of the experimental group (compound α tricalcium phosphate with monocalcium citrate bone cement) are significantly different (P = 0.008) for the initial stability (ISQ value) of the material, but the material during wound healing compared with control group (hydroxyapatite complex, β tricalcium phosphate and collagen) easily exposed (group 4 weeks 25%, 100% of group 8 weeks, 12 weeks group 33.33% ) , 8 weeks of the experimental group compared to the stability of the implant ISQ values of the control group (P = 0.005) had a poor performance at other time points no significant difference PTV values (P = 0.043) . In 8 weeks group at different time points following the experimental group 12 weeks ISQ circumferential value (P = 0.012) compared to, PTV values (P = 0.044) had poorer performance values PTV group 8 weeks 4 weeks compared to group (P = 0.026) and bone mass tomography (Micro-CT bone volume) (P = 0.046) poor performance, there was no significant difference at other time points. Also in the fluorescein-labeled bone section shows the experimental group (compound α tricalcium phosphate with monocalcium citrate bone cement) with heavy lateral subperiosteal reaction and bone regeneration lead to widen of the ridge rather different from the control group and blank group. Based on these findings of the results, we thus concluded that we have developed a new injectable α-tricalcium phosphate bone cement with initial high flowability and subsequent hardness which maybe a pontenial bone graft material intraorally. Furthermore, functional investigation on such new cement revealed prolonged resroption time and compromised results indicated composition medication may be done for the meet of needs in dental application in the future.