Objective. The objective of this study is to test the efficacy of the biodegradable mesh as an alternative fixation device to the titanium mesh for support of onlay particulate, bone and cancellous, marrow (PBCM) grafts. Two parameters were evaluated: (1) Bone graft volume maintenance; and (2) Calcified tissue surface area and distribution. Methods. 12 New Zealand white rabbits were used and divided equally into two groups. In both groups, endochondral, cancellous bone graft was harvested from the anterior ilium. The bone graft was then compressed and placed as an onlay onto the lateral aspect of the mandible using two chambers for each animal. In the control group, the chambers were made of titanium, however in the test group the chambers were made of poly L-lactide, polyglycolide and trimethylene carbonate mesh (Inion GTR(TM) Finland), and thereafter the chambers were fixed to the mandible. The animals were then sacrificed after eight weeks postoperatively, and then Micro-CT imaging was performed for the entire sample in order to determine the total volume of calcified tissue present under each chamber. In addition, Histologic sections were obtained from each chamber, and thereafter stained using Toluidine blue and Von Kossa for the purpose of histomorphometric analysis in order to determine the calcified tissue surface area. Results. When comparing the data from both the titanium (Ti) and the biodegradable mesh (PLA) groups, Micro CT analysis showed no significant statistical difference (P-value = 0.546) with regard to the percentage of bone found under the chambers (Ti 15.0% and PLA 13.83%). Interestingly, neither did the histomorphometric analysis show any significant statistical deference (P-value = 0.8272) with regard to the percentage of calcified tissue surface area (Ti 16.86% and PLA 16.17%). Moreover, this calcified tissue was also found to be evenly distributed in both groups. Conclusion. Biodegradable mesh made of poly L-lactic and polyglycolic acid copolymers appears to be an appropriate alternative to the Ti mesh for support of PBCM bone grafts. However, further clinical trails should be conducted to confirm these findings.

No description available.

A doença arterial coronariana vem sendo a maior causa de mortalidade no mundo, a angioplastia com implante de stent é uma estratégia importante nestes casos. Estudos apontam a biodegradabilidade, imobilização de antiproliferativos e moléculas bioativas nos stents, como características das futuras gerações destes dispositivos. Dentre estas, o ácido hialurônico contribui para a diminuição da agregação e proliferação de células entre as camadas da artéria e o dispositivo implantado. Foram desenvolvidos modelos de stents coronários biorreabsorvíveis de poli(-L-ácido láctico) (PLLA) com enxertia de ácido hialurônico (HA) em poli(-ácido lático co-ácido glicólico) (PLGA) e poli(L-D-ácido lático) (PLDLA). Os modelos foram caracterizados quanto suas propriedades térmicas, mecânicas e de superfície. O PLDLA e PLGA com enxertia de HA modificado com dihidrazida adípica (ADH) apresentaram características de superfície mais hidrofílicas, ideais para material de revestimento dos dispositivos. Desta forma, este trabalho possibilitou o desenvolvimento dos modelos físicos biorreabsorvíveis, com dimensões semelhantes aos stents coronários, feitos de PLLA, revestidos com PLGA e PLDLA com enxertia de HA e HAADH, e estáveis aos processos de esterilização por radiação ultravioleta e plasma de peróxido de hidrogênio. / Coronary artery disease has been world´s leading cause of death and angioplasty stent implantation is an important strategy in these cases. Studies indicate that the biodegradability, immobilization of antiproliferatives and bioactive molecules in stents are characteristics of future generations of these medical devices. Amongst them, hyaluronic acid (HA) contributes to the decrease of the aggregation and proliferation of cells between artery layers and implanted device. For this purpose, poly (L-lactic acid) (PLLA) bioresorbable coronary stents with HA grafting in poly (lactic acid-co-glycolic acid) (PLGA) and poly (LD- (PLDLA) were developed. The models were characterized as their thermal, mechanical and surface properties. PLDLA and PLGA with adipic dihydrazide (ADH) modified HA grafting presented more hydrophilic surface characteristics, ideal as coating material of this devices. This project allowed the development of bioresorbable physical models with similar dimensions to coronary stents, made of PLLA, coated with PLGA and PLDLA with hyaluronic acid grafting, stable to ultraviolet radiation and plasma sterilization with hydrogen peroxide processes.

研究背景：常规骨科临床在治疗大段骨缺损时需要移植骨和（或）支架材料，尤其复合有治疗性生物活性成分的复合材料尤为理想。本研究的策略在于发展开发一种具有生物活性和生物降解特性的的合并有植物小分子icaritin（外源性生长因子）或者骨形态发生蛋白2（BMP-2, 内源性生长因子）的复合骨支架用于骨再生。基于聚乳酸乙交酯共聚物和磷酸三钙，我们利用先进的快速成型技术编制了新型的符合有BMP-2 或者icaritin 的支架材料， 命名为PLGA/TCP （ 对照材料组） ，PLGA/TCP/BMP-2（BMP-2 编织复合治疗材料组）， PLGA/TCP/icaritin （低，中，高剂量icaritin 编织复合治疗材料组）。 / 研究目标：本研究的总体目标是通过系统的体外实验和兔骨缺损的体内实验，建立和评估一种优化的复合递送系统，用于骨再生的应用。体内效果的研究体现在终点关于合并有外源性生长因子icaritin 和内源性生长因子BMP-2 的复合材料之间的比较研究。 / 材料和方法：低温快速成型机器用于复合材料的编制。PLGA 和TCP 作为基本载体材料，icaritin 和BMP-2 作为具有生物活性的外源性和内源性生长因子，分别进行编织复合。最终编织复合的支架材料命名为P/T 对照组，P/T/BMP-2 和低，中，高剂量P/T/icaritin 治疗组。另外，我们通过液体完全浸泡并在真空橱内干燥24 小时的方法制备了BMP-2 和icaritin 浸泡复合支架材料，分别是P/T+BMP-2(阳性对照组)和中剂量P/T+icaritin(比较组)。体外成骨潜能是通过兔骨髓干细胞和支架材料共培养的方法检测细胞接种，增殖效率，碱性磷酸酶活性，钙沉积以及成骨基因定量mRNA 表达检测。兔尺骨双侧阶段性缺损并植入复合支架材料的模型用于探讨支架材料体内成骨和成血管功效，影像学和活体检测CT 技术用于评估骨再生；借助CT的血管造影术和组织学检测新生血管；动态核磁共振技术用于检测骨缺损局部血液灌注功能，以及宿主组织和支架材料之间的相互作用。 / 研究结果： 对编织的支架材料的体外特性和成骨潜能进行鉴定和评估。显微CT 定量结果显示此支架材料具有互联大孔隙，平均孔隙率75±3.27%，平均孔径458±25.6μm。和对照组，icaritin 浸泡复合组，BMP-2 编织复合组比较，在icaritin 编织复合支架材料（n=6, p<0.05）特别是中剂量组（n=6, p<0.01）中，与材料共培养的兔骨髓干细胞（BMSCs）表现了较高的细胞接种效率，碱性磷酸酶活性和上调的胶原酶I，骨桥蛋白mRNA 表达，以及较多的钙结节沉积。同时，BMP-2 浸泡复合组表现了最佳的效果（n=6, p<0.01）。兔尺骨缺损模型体内试验结果显示，术后2，4，8周影像学和显微CT 显示，和对照组，icaritin 浸泡复合组，BMP-2 编织复合组比较，icaritin 编织复合支架材料（n=6, p<0.05）特别是中剂量组材料（n=6, p<0.01）植入的骨缺损区域有更多新生成骨。BMP-2 浸泡复合组表现了最多的新骨形成（n=6,p<0.01）。组织学结果同样也验证了在icaritin 编织复合支架材料（n=6, p<0.05）特别是中剂量组（n=6, p<0.01）中，存在较多的骨样组织和典型的板层骨。BMP-2 浸泡复合组也具有最多的新骨组织生成（n=6, p<0.01）。此外， 在icaritin 编织复合支架材料（n=6, p<0.05）尤其中剂量组（n=6, p<0.01）中，借助显微CT 的血管造影术检测发现，骨缺损区域出现较大的新生血管体积，动态核磁共振检查发现较好的局部血液灌注功能。在三种icaritin 剂量浓度的编织复合材料组之间比较，我们发现中浓度icaritin 复合比例的编织复合材料组显示了最佳的成骨潜能。 / 研究结论： 编织复合有外源性植物分子icaritin 的PLGA/TCP 支架材料在体内体外试验中均表现了预期的成骨分化潜能和骨再生能力，尤其是中剂量icaritin 编织复合材料。传统的应用前做体外复合的BMP-2 浸泡复合支架材料和更具吸引力和方便应用的植物分子icaritin 编织复合支架材料，都可以较好的增强骨修复，这很可能为新型生物复合材料潜在的临床有效性验证提供很好的基础。 / Background: Treatment of large bone defect in routine orthopaedic clinics requires bonegrafting and/or scaffold materials, especially desirable with composite material combined with therapeutic and bioactive agents for achieving better treatment outcome. The strategy of this study was to develop such a bioactive biodegradable composite bone scaffold incorporating a phytomolecule icaritin as an exogenous growth factor or bone morphogenetic protein-2 (BMP-2) as a known endogenous growth factor for bone regeneration. Based on polylactide-co-glycolide (PLGA) and Tricalcium Phosphate (TCP), we fabricated innovative BMP-2 or icaritin incorporated scaffold materials, namely PLGA/TCP (Control group), PLGA/TCP/BMP-2 and PLGA/TCP/low-, middle-, and high-icaritin with three different dosages of icaritin (Treatment groups) by an advanced prototyping technology. / Aims: The overall aim of the study was to establish and evaluate a local delivery system with slow release of bioactive agents for acceleration of bone regeneration in a bone defect model in rabbits. In vivo efficacy study served as end-point of this comparative study between composite scaffold incorporating exogenous growth factor icaritin and endogenous growth factor BMP-2. / Materials & Methods: Composite scaffolds were fabricated at -28ºC by a lowtemperature rapid-prototyping machine. PLGA and TCP were used as basic carrier materials, and icaritin or BMP-2 was incorporated as exogenous or endogenous bioactive growth factors, respectively. The incorporated scaffolds were named by PLGA/TCP (P/T, Control group), PLGA/TCP/BMP-2 and PLGA/TCP/low-, middle-, and high-icaritin (Treatment groups). In addition, we prepared BMP-2 and icaritin loading scaffolds, namely PLGA/TCP+BMP-2 as positive control group and PLGA/TCP+middle-icaritin as comparative group by entire immersion in the solution and dry in vacuum cabinet for 24 hours. In vitro osteogenic potentials of the designed bioactive composite scaffolds were tested in scaffold-co-cultured rabbit bone marrow stem cells (BMSCs) for measurement of cell seeding and proliferation efficiency, alkaline phosphatase (ALP) activity, calcium deposition, and quantitative mRNA expression of relative osteogenic genes. In vivo efficacy investigation was designed to evaluate osteogenesis and angiogenesis in a bilateral ulna bone segmental defect model implanted with composite scaffold in rabbits, with radiography and in vivo micro-CT for studying new bone regeneration and micro-CT-based angiography and histology for neovascularization, dynamic MRI for local blood perfusion function, as well as host tissue and scaffold material interactions. / Results: The in vitro characterization and osteogenic potential of the fabricated scaffolds were performed and confirmed, respectively. Micro-CT quantitation showed that the scaffolds had interconnected macropores with an average porosity of 75±3.27 % and pore size or diameter of 458±25.6 μm. Compared to P/T, P/T+icaritin and P/T/BMP-2 scaffolds, P/T/icaritin scaffolds (n=6, p<0.05), especially P/T/middle-icaritin (n=6, p<0.01) presented higher cell seeding efficiency, ALP activity and calcium nodules and up-regulated mRNA expressions of Collagen type I and Osteopontin of co-cultured BMSCs. P/T+BMP-2 showed the best osteogenic effects among all groups (n=6, p<0.01). In vivo measurement of x-ray and micro-CT in rabbit ulna bone defect model at week 2, 4 and 8 post-surgery showed more newly formed bone in the defects treated with P/T/icaritin scaffolds (n=6, p<0.05), especially P/T/middle-icaritin scaffold (n=6, p<0.01) compared with that of P/T, P/T+icaritin and P/T/BMP-2 groups. P/T+BMP-2 also showed the best bone formation among all groups (n=6, p<0.01). Histological results also demonstrated that there were more osteoid tissues and typical lamellar bone in surface and internal of the implants, as well as along the adjacent host bone in P/T/icaritin groups (n=5, p<0.05), especially P/T/middle-icaritin group (n=6, p<0.01). P/T+BMP-2 group showed the most newly formed bone (n=6, p<0.01). In addition, newly formed vessels in the defects were identified with micro-CT-based angiography and functionally supported by dynamic MRI for reflecting blood perfusion. The results showed more ingrowing new vessels in P/T/icaritin groups (n=6, p<0.05), especially P/T/middle-icaritin group (n=6, p<0.01), compared to P/T and P/T/BMP-2 groups. For comparing dose effects among three scaffolds incorporating different concentration of icaritin, we found that middle dose PLGA/TCP/icaritin composite scaffold showed the best osteogenic potential. / Conclusion: PLGA/TCP scaffolds incorporating exogenous phytomolecule icaritin demonstrated the desired osteogenic differentiation potential and bone regeneration capability as investigated in vitro and in vivo, where the middle dose of icaritin incorporating PLGA/TCP composite scaffold showed the best effects. These findings may form a good foundation for potential clinical validation of this innovative bioactive composite scaffold with either conventional endogenous BMP-2 for in vitro loading before application or more attractively and user-friendly incorporated with exogenous phytomolecule icaritin as a ready product for enhancing bone defect repair. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Chen, Shihui. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 173-198). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / Acknowledgements --- p.viii / Abstract --- p.x / 中文摘要 --- p.xiii / List of Abbreviations --- p.xvi / List of Tables --- p.xix / List of Figures --- p.xx / Journal Publications --- p.xxv / Journal Supplements --- p.xxv / Conference Abstracts --- p.xxvi / Chapter Chapter 1 --- Introduction / Chapter 1.1 --- Bone Defect in Orthopaedics --- p.2 / Chapter 1.2 --- Human Skeletons --- p.2 / Chapter 1.2.1 --- Bone Types and Function --- p.2 / Chapter 1.2.2 --- Bone Development --- p.4 / Chapter 1.2.3 --- Bone Physiology and Structure --- p.6 / Chapter 1.2.4 --- Bone Specific Markers --- p.7 / Chapter 1.2.5 --- Bone Cells --- p.9 / Chapter 1.2.6 --- Bone Marrow Stromal Cells --- p.12 / Chapter 1.3 --- Bone Regeneration and Remodeling --- p.13 / Chapter 1.3.1 --- Bone Defect Healing --- p.13 / Chapter 1.3.2 --- Non-union and Segmental Defect --- p.15 / Chapter 1.3.3 --- Bone Defect Treatment --- p.16 / Chapter 1.4 --- Angiogenesis in Bone Healing --- p.19 / Chapter 1.4.1 --- Blood Vessels Formation Process --- p.20 / Chapter 1.4.2 --- Growth Factor in Angiogenesis --- p.21 / Chapter 1.5 --- Biomaterials in Bone Tissue Engineering --- p.22 / Chapter 1.6 --- Scaffold-Based Therapy --- p.23 / Chapter 1.6.1 --- Bone Grafts --- p.23 / Chapter 1.6.1.1 --- Autografts --- p.23 / Chapter 1.6.1.2 --- Allografts --- p.25 / Chapter 1.6.2 --- Bone Graft Substitutes --- p.25 / Chapter 1.6.2.1 --- Bone Formation in Porous Scaffolds --- p.25 / Chapter 1.6.2.2 --- Degradable Polymers --- p.27 / Chapter 1.6.2.3 --- Non-Degradable Polymers --- p.29 / Chapter 1.6.2.4 --- Ceramics --- p.29 / Chapter 1.6.2.5 --- Bioactive Composite Materials --- p.30 / Chapter 1.7 --- Growth Factor-Based Therapy --- p.31 / Chapter 1.7.1 --- Endogenous Growth Factor--Bone Morphogenetic Proteins --- p.31 / Chapter 1.7.2 --- Exogenous phytomoleculeIcaritin--Icaritin --- p.31 / Chapter 1.7.3 --- Delivery of Growth Factor in Tissue Engineering --- p.34 / Chapter 1.8 --- Fabrication of Porous Composite Scaffolds --- p.37 / Chapter 1.8.1 --- Architectural Parameters of Bone Scaffolds --- p.37 / Chapter 1.8.2 --- Three-Dimensional Scaffold Fabrication --- p.37 / Chapter 1.9 --- Animal Models for Testing Bone Defects Healing --- p.39 / Chapter Chapter 2 --- Research Rationale and Study Objectives / Chapter 2.1 --- Research Rationale --- p.42 / Chapter 2.2 --- Study Objectives --- p.46 / Chapter Chapter 3 --- Bioactive Composite Scaffolds: Preparation, Morphology and Release Assay / Chapter 3.1 --- Introduction --- p.49 / Chapter 3.2 --- Materials and Methods --- p.50 / Chapter 3.2.1 --- Materials --- p.50 / Chapter 3.2.2 --- Fabrication of PLGA/TCP Incorporating BMP-2 or Icaritin --- p.51 / Chapter 3.2.3 --- Morphological Analysis of Composite Scaffolds --- p.53 / Chapter 3.2.3.1 --- Analysis of Porosity and Macropores Diameter Using High-resolution Micro-CT --- p.53 / Chapter 3.2.3.2 --- Analysis of Surface Morphology and Elements Composition Using Scanning Electron Microscopy --- p.54 / Chapter 3.2.4 --- Icaritin Content Assay in PLGA/TCP Scaffolds Incorporating Icaritin --- p.54 / Chapter 3.2.5 --- Preparation of PLGA/TCP Scaffold Coating BMP-2 or Icaritin --- p.55 / Chapter 3.2.6 --- In vitro Release Assay --- p.55 / Chapter 3.2.6.1 --- Icaritin Release from Scaffolds of PLGA/TCP Incorporating Icaritin --- p.55 / Chapter 3.2.6.2 --- BMP-2 Release from Scaffolds of PLGA/TCP Incorporating/Coating BMP-2 --- p.56 / Chapter 3.2.7 --- Mechanical Properties of Composite Scaffolds --- p.56 / Chapter 3.2.8 --- Statistical Analysis --- p.57 / Chapter 3.3 --- Results --- p.57 / Chapter 3.3.1 --- Morphological Analysis of Composite Scaffolds --- p.57 / Chapter 3.3.1.1 --- Porosity and Macroscopic Diameter --- p.57 / Chapter 3.3.1.2 --- Surface Morphology and Elements Composition --- p.58 / Chapter 3.3.2 --- Icaritin Content in Scaffolds of PLGA/TCP Incorporating Icaritin --- p.60 / Chapter 3.3.3 --- Icaritin Release from Scaffolds of PLGA/TCP Incorporating Icaritin --- p.60 / Chapter 3.3.4 --- BMP-2 Release from Scaffolds of PLGA/TCP Incorporating/Coating BMP-2 --- p.61 / Chapter 3.3.5 --- Mechanical Properties of Composite Scaffolds --- p.63 / Chapter 3.4 --- Discussion --- p.64 / Chapter 3.5 --- Summary --- p.71 / Chapter Chapter 4 --- Bioactive Composite Scaffolds: In vitro Degradation and Characterization Studies / Chapter 4.1 --- Introduction --- p.73 / Chapter 4.2 --- Materials and Methods --- p.74 / Chapter 4.2.1 --- Preparation of Composite Scaffolds for in vitro Degradation Assay --- p.74 / Chapter 4.2.2 --- Characterizations --- p.75 / Chapter 4.2.2.1 --- Scaffold Volume Changes --- p.75 / Chapter 4.2.2.2 --- Scaffold Weight Changes --- p.75 / Chapter 4.2.2.3 --- pH Value Changes --- p.75 / Chapter 4.2.2.4 --- Calcium Ion Release from Scaffolds --- p.76 / Chapter 4.2.3 --- Mechanical Properties Changes --- p.76 / Chapter 4.2.4 --- Statistical Analysis --- p.77 / Chapter 4.3 --- Results --- p.77 / Chapter 4.3.1 --- Volume Decrease --- p.78 / Chapter 4.3.2 --- Weight Loss --- p.78 / Chapter 4.3.3 --- pH Value Reduction --- p.79 / Chapter 4.3.4 --- Calcium Ion Release --- p.79 / Chapter 4.3.5 --- Mechanical Properties --- p.80 / Chapter 4.4 --- Discussion --- p.81 / Chapter 4.5 --- Summary --- p.84 / Chapter Chapter 5 --- In vitro Evaluation of Bone Marrow Stem Cells (BMSCs) Growing on Bioactive Composite Scaffolds / Chapter 5.1 --- Introduction --- p.87 / Chapter 5.2 --- Materials and Methods --- p.90 / Chapter 5.2.1 --- Preparation of Composite Scaffolds for in vitro Evaluation --- p.90 / Chapter 5.2.2 --- BMSCs Seeding Rate and Proliferation on Composite Scaffolds --- p.90 / Chapter 5.2.3 --- Alkaline Phosphate (ALP) Activity Assay --- p.92 / Chapter 5.2.4 --- Osteogenic Gene Expression Assay Using Quantitative Real-time PCR --- p.92 / Chapter 5.2.5 --- Calcium Deposition Assay Using Alizarin Red Staining --- p.93 / Chapter 5.2.6 --- Statistical Analysis --- p.94 / Chapter 5.3 --- Results --- p.94 / Chapter 5.3.1 --- Cells Seeding Efficiency and Proliferation --- p.94 / Chapter 5.3.2 --- ALP Activity --- p.97 / Chapter 5.3.3 --- Osteogenic Gene mRNA Expression --- p.97 / Chapter 5.3.4 --- Calcium Deposition --- p.98 / Chapter 5.4 --- Discussion --- p.99 / Chapter 5.5 --- Summary --- p.102 / Chapter Chapter 6 --- In vivo Evaluation of Bone Healing in Bone Defect Model Implanted with Bioactive Composite Scaffolds / Chapter 6.1 --- Introduction --- p.105 / Chapter 6.2 --- Materials and Methods --- p.106 / Chapter 6.2.1 --- Preparation of Composite Scaffolds for Implantation --- p.106 / Chapter 6.2.2 --- Establishment of Ulna Bone Segmental Defect in Rabbits --- p.107 / Chapter 6.2.3 --- Radiographic Evaluation of New Bone Area Fraction --- p.109 / Chapter 6.2.4 --- XtremeCT Evaluation of New Bone Formation and Bone Mineral Density (BMD) --- p.110 / Chapter 6.2.5 --- Histological Evaluation of New Bone Formation --- p.111 / Chapter 6.2.6 --- Evaluation of Rate of New Bone Formation and Mineral Apposition Rate (MAR) --- p.114 / Chapter 6.2.7 --- Evaluation of Neovascularization Using Micro-CT-based Microangiography --- p.116 / Chapter 6.2.8 --- Blood Perfusion Function Using Dynamic Magnetic Resonance Imaging (MRI) --- p.119 / Chapter 6.2.9 --- Statistical Analysis --- p.120 / Chapter 6.3 --- Results --- p.121 / Chapter 6.3.1 --- Radiographic Area Fraction of New Bone Formation --- p.123 / Chapter 6.3.2 --- XtremeCT New Bone Volume Fraction and BMD --- p.128 / Chapter 6.3.3 --- Histological New Bone Fraction --- p.133 / Chapter 6.3.4 --- Rate of New Bone Formation and MAR --- p.136 / Chapter 6.3.5 --- New Vessels Volume Evaluated Using Micro-CT-Based Microangiography --- p.140 / Chapter 6.3.6 --- Dynamic Blood Perfusion Function --- p.144 / Chapter 6.4 --- Discussion --- p.146 / Chapter 6.5 --- Summary --- p.151 / Chapter Chapter 7 --- Summaries, Conclusions, Limitations and Future Studies / Chapter 7.1 --- Introduction --- p.153 / Chapter 7.2 --- Bioactive Composite Scaffolds: Preparation, Morphology and in vitro Release Evaluation --- p.155 / Chapter 7.3 --- Bioactive Composite Scaffolds: in vitro Degradation and Characterization Studies --- p.159 / Chapter 7.4 --- In vitro Evaluation of the Response of Bone Marrow Stem Cells Growing on Bioactive Composite Scaffolds --- p.160 / Chapter 7.5 --- In vivo Evaluation of Bone Healing in Bone Defect Model Implanted with Bioactive Composite Scaffolds --- p.162 / Chapter 7.6 --- Evaluation of Dose-dependent Effects of Icaritin Mechanical Property, Degradation, and Osteogenic Potentials --- p.164 / Chapter 7.7 --- Conclusions --- p.170 / Chapter 7.8 --- Limitations and Future Studies --- p.171 / Chapter 7.9 --- References --- p.173 / Chapter 7.10 --- Appendix --- p.199 / Chapter 7.10.1 --- Animal Licence and Ethics --- p.199 / Chapter 7.10.2 --- Safety Approval --- p.201 / Chapter 7.10.3 --- Journal Supplements --- p.202 / Chapter 7.10.4 --- Conference Abstracts--Posters --- p.205 / Chapter 7.10.5 --- Conformation of Paper Submission --- p.208 / Chapter 7.10.6 --- Published Paper --- p.209

Orientador: Renato Mazzonetto / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-12T19:06:05Z (GMT). No. of bitstreams: 1 Kluppel_LeandroEduardo_D.pdf: 4554171 bytes, checksum: a4446185367f8bc629d9038fc03b2889 (MD5) Previous issue date: 2008 / Resumo: O objetivo do presente estudo in vivo foi avaliar histologicamente, de forma comparativa, o emprego de parafusos absorvíveis baseados no polímero poli(L-co-D,L ácido lático) 70:30 sintetizado por um laboratório nacional, para fixação de enxertos ósseos autógenos em tíbias de coelhos. Como controle foram utilizados parafusos à base de liga de titânio (Ti-6Al-4V/Grau V) de mesmas dimensões. Para tanto, foram selecionados 15 coelhos adultos, albinos, da raça Nova Zelândia, machos, com idade aproximada de 6 meses e peso variando entre 3,8 e 4,5 kg no momento do procedimento cirúrgico. De cada animal foram removidos 2 enxertos ósseos em espessura total da calota craniana, sendo um deles fixado à tíbia com parafuso absorvível e o outro com parafuso metálico. Os animais foram divididos em 3 grupos, de acordo com os períodos de sacrifício: 3, 8 e 16 semanas pós-operatórias. Após o processamento histológico, as lâminas foram coradas com hematoxilina e eosina e submetidas à análise histológica descritiva em microscopia óptica. Como resultado encontrou-se que o sistema de fixação baseado em polímero apresentou um comportamento histológico bastante semelhante ao sistema metálico. Em ambos os grupos o enxerto encontrava-se incorporado, ocorrendo neoformação óssea em sua interface com o leito receptor. Em nenhum dos grupos foi evidenciado processo inflamatório indesejável ou reação a corpo estranho. Baseando-se nos achados histológicos para o modelo experimental e metodologia empregada, pode-se concluir que o sistema de fixação baseado no polímero poli(L-co-D,L ácido lático) 70:30 é efetivo para a fixação de enxertos ósseos autógenos, com resultados comparáveis ao materiais à base de liga de titânio. / Abstract: The aim of the present in vivo study was to evaluate histologically, by comparative means, the use of resorbable screws based on poli(L-co-D,L lactide) 70:30, manufactured by a brazillian laboratory, used for fixation of autogenous bone grafts in rabbit tibiae. As a control, titanium (Ti-6Al-4V Grade V) screws were used. For this purpose, fifteen white New Zeland male rabbits, with age of 6 months and weight between 3.8 - 4.5 Kg were used. Of each animal, 2 total thickness bone grafts were removed from the cranial vault and one of them was stabilized with resorbable screw while the other was stabilized with the metallic one. Animals were divided in 3 groups, according to the sacrifice period: 3, 8 and 16 week postoperatively. After histological processing, cuts were corated with hematoxilin and eosin and submited to descriptive histological analysis under light microscopy. As a result it was found that the fixation system based on polimer showed a histological behavior similar to the metallic system. For both groups bone graft was incorporated, with the presence of bone neoformation between this and the receptor site. In none of the groups undesirable inflammatory process or foreign body reaction was observed. Based on histological findings and respecting this experimental model it is possible to conclude that that the internal fixation system based on the poli(L-co-D,L lactide) 70:30 polymer is effective for fixation of autogenous bone grafts, offering results that are comparable the titanium fixation systems. / Doutorado / Cirurgia e Traumatologia Buco-Maxilo-Faciais / Doutor em Clínica Odontológica

Orientador: Renato Mazzonetto / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-09T17:30:26Z (GMT). No. of bitstreams: 1 Stabile_GlaykonAlexVitti_D.pdf: 16450552 bytes, checksum: 1cc54a5190181529261a0a9f364bf290 (MD5) Previous issue date: 2007 / Resumo: O propósito deste estudo foi avaliar histologicamente in vivo de forma comparativa a reação tecidual local ao emprego de um sistema de fixação interna reabsorvível baseado no polímero poli(L-co-D,L ácido lático) 70:30 sintetizado por um laboratório nacional, utilizado como fixação interna em tíbias de coelho, utilizando como controle um sistema de fixação interna baseado em uma liga de titânio (Ti-6Al-4V/Grau V) de mesmas dimensões. Foram utilizados 15 coelhos adultos, albinos, da raça Nova Zelândia, fêmeas, com idade aproximada de 6 meses e peso variando entre 3,8 e 4,5 kg no momento do procedimento cirúrgico. Cada animal recebeu ao mesmo tempo o sistema reabsorvível e o sistema metálico ambos compostos por uma placa de 2 elos e dois parafusos do sistema 2.0 de 12 mm instalados de modo posicional bicortical. Os animais foram divididos aleatoriamente em 3 grupos segundo os seguintes períodos de sacrifício: 3, 8 e 16 semanas pós-operatórias. Após processamento laboratorial de rotina as peças foram coradas com hematoxilina e eosina e submetidas à análise histológica descritiva. Como resultado encontrou-se que o sistema de fixação baseado em polímero apresentou um comportamento histológico bastante semelhante ao sistema metálico. Não evidenciou-se em nenhum período de sacrifício para ambos os grupos a presença de processo inflamatório indesejável ou reação a corpo estranho. Baseando-se nos achados histológicos para o modelo experimental e metodologia empregada, pode-se concluir que o sistema de fixação baseado no polímero poli(L-co-D,L ácido lático) 70:30 apresentou satisfatória biocompatibilidade com o leito receptor / Abstract: The purpose of this in vivo study was to evaluate histologically, by comparative means, the local tissue reaction to the resorbable internal fixation based on poli(L-co-D,L lactide) 70:30, manufactured by a brazillian laboratory. The material was used as an internal fixation device in rabbit tibia. Titanium internal fixation system (Ti-6Al-4V Grade V) with the same dimensions was used as a control group. Fifteen white New Zeland female rabbits, with age of 6 months and weight between 3.8 ¿ 4.5 Kg were used. Each animal received, at the same time, the resorbable and the metalic system. Both were constituted by one plate and two screws of 2.0 system and 12 mm in length wich were installed bicortically in a positional way. The animals were randomly divided into three groups and sacrificed in the following periods: 3, 8 and 16 weeks postoperative. After routine laboratorial process and coloration by hematoxilin and eosin the sections were analyzed by descriptive histology. The results showed no relevant differences between internal fixation system based on resorbable polymer and the metallic system. There was no evidence of moderate or severe inflammatory process as well as foreign body reaction in both fixation materials on the evaluated periods. Based on histological findings to the experimental model and methods we can conclude that the internal fixation system based on the poli(L-co-D,L lactide) 70:30 polymer is biocompatible within the receptor site / Doutorado / Cirurgia e Traumatologia Buco-Maxilo-Faciais / Doutor em Clínica Odontológica

A doença arterial coronariana vem sendo a maior causa de mortalidade no mundo, a angioplastia com implante de stent é uma estratégia importante nestes casos. Estudos apontam a biodegradabilidade, imobilização de antiproliferativos e moléculas bioativas nos stents, como características das futuras gerações destes dispositivos. Dentre estas, o ácido hialurônico contribui para a diminuição da agregação e proliferação de células entre as camadas da artéria e o dispositivo implantado. Foram desenvolvidos modelos de stents coronários biorreabsorvíveis de poli(-L-ácido láctico) (PLLA) com enxertia de ácido hialurônico (HA) em poli(-ácido lático co-ácido glicólico) (PLGA) e poli(L-D-ácido lático) (PLDLA). Os modelos foram caracterizados quanto suas propriedades térmicas, mecânicas e de superfície. O PLDLA e PLGA com enxertia de HA modificado com dihidrazida adípica (ADH) apresentaram características de superfície mais hidrofílicas, ideais para material de revestimento dos dispositivos. Desta forma, este trabalho possibilitou o desenvolvimento dos modelos físicos biorreabsorvíveis, com dimensões semelhantes aos stents coronários, feitos de PLLA, revestidos com PLGA e PLDLA com enxertia de HA e HAADH, e estáveis aos processos de esterilização por radiação ultravioleta e plasma de peróxido de hidrogênio. / Coronary artery disease has been world´s leading cause of death and angioplasty stent implantation is an important strategy in these cases. Studies indicate that the biodegradability, immobilization of antiproliferatives and bioactive molecules in stents are characteristics of future generations of these medical devices. Amongst them, hyaluronic acid (HA) contributes to the decrease of the aggregation and proliferation of cells between artery layers and implanted device. For this purpose, poly (L-lactic acid) (PLLA) bioresorbable coronary stents with HA grafting in poly (lactic acid-co-glycolic acid) (PLGA) and poly (LD- (PLDLA) were developed. The models were characterized as their thermal, mechanical and surface properties. PLDLA and PLGA with adipic dihydrazide (ADH) modified HA grafting presented more hydrophilic surface characteristics, ideal as coating material of this devices. This project allowed the development of bioresorbable physical models with similar dimensions to coronary stents, made of PLLA, coated with PLGA and PLDLA with hyaluronic acid grafting, stable to ultraviolet radiation and plasma sterilization with hydrogen peroxide processes.

INTRODUCTION: For persons with diabetes, surgery is fraught with complications; of primary concern is postoperative infection. A postoperative infection rate of up to 13% has been noted in patients with diabetes undergoing elective surgical procedures compared with less than 3% in nondiabetic populations. OBJECTIVE: The objective of this study was to provide preliminary evaluation of the efficacy of a novel bioresorbable microfilm matrix (20 µm thick) containing very low amounts of silver (0.16 mg/in²) in preventing surgical site infections when placed at the level of subcutaneous tissue and dermis prior to primary closure in the patient with diabetes undergoing elective surgery. MATERIALS AND METHODS: Twenty-two patients with diabetes undergoing nonemergent or elective foot or ankle surgery and who met at least 1 of the following 6 criteria were included in the study: neuropathy, infection, open wound, history of recurrent infection, nonhealing wound, or peripheral vascular disease. Patients underwent amputation, removal of exostosis, midfoot bone removal, Achilles tendon repair, bunionectomy, or an elevating osteotomy with primary closure of the wound. After hemostasis was obtained and subcutaneous closure achieved, if applicable, the bioresorbable microfilm matrix was applied just deep to the incision at the level of subcutaneous tissue and dermis, and the incision primarily closed. A nonadherent cover dressing was applied over the suture line, and routine follow-up was scheduled for 3 to 5 days later. RESULTS: No patient exhibited signs of infection at initial follow-up, and all adherent patients achieved complete healing during the 3-month follow-up period. Eighteen patients healed at a rate typical for the respective procedure. In 2 patients, time to healing was delayed secondary to weight-bearing dehiscence. Two patients were not included in the results secondary to multiple infractions of nonadherence with the postoperative protocol. CONCLUSIONS: The application of microfilm matrix in surgical incisions at the level of subcutaneous tissue and dermis prior to primary closure is safe for and has the potential to prevent postoperative surgical site infections in at-risk patients with diabetes..

O padrão ouro no tratamento cirúrgico das fraturas de tornozelo são as sínteses metálicas, sejam de titânio ou aço. Os implantes bioabsorvíveis foram desenvolvidos para evitar o efeito do stress shielding, ou escudo de carga, e a retirada de material de síntese. O uso de materiais absorvíveis é bem documentado, e com bons resultados em grande número de fraturas craniofaciais. O objetivo deste estudo foi comparar os resultados funcionais de fraturas de tornozelo tratadas com placas metálicas e absorvíveis. Os pacientes foram randomizados e seguidos de forma prospectiva em dois grupos, metálico e absorvível. No período pós operatório imediato os pacientes foram imobilizados com tala gessada por uma semana, substituída por órtese removível por mais 4 semanas. Carga parcial foi autorizada com 3 semanas, e carga total com 6 semanas. Dezenove pacientes foram seguidos por nove meses, e avaliados radiográfica e funcionalmente aos 6 e 9 meses. Todos consolidaram entre 8 e 12 semanas. A recuperação funcional foi similar nos dois grupos. Aos 6 meses, três pacientes no grupo metálico queixaram-se de problemas locais, e tiveram seus implantes removidos. Um paciente do grupo absorvível teve uma deiscência da sutura, tratado com boa evolução. Aos 9 meses foi aplicado o escore da AOFAS para todos os pacientes. Os resultados funcionais foram semelhantes nos dois grupos, após a retirada de implante de três pacientes no grupo metálico. Os implantes absorvíveis permitiram resultados clínicos e funcionais semelhantes aos metálicos em fraturas de tornozelo / The current gold standard fixation system for surgical ankle fractures are the metallic implants, steel or titanium made. Resorbable implants have been developed to avoid stress shielding and a new surgery for implant removal, common with metal implants. Use of resorbable implants is well documented in the literature for a range of craniofacial fractures, with good results. The purpose of this study was to compare the outcome of ankle fractures using biodegradable and metal plates. Patients were randomly and prospectively treated with resorbable or metal fixation system. Post-operatively, the ankle was immobilized with a plaster cast for 1 week, removable cast for other 4 weeks. Half and full weight bearing were allowed at weeks 3 and 6. nineteen patients were followed for 9 months. Functional recovery was similar in both groups at 6 and 9 months, three patients in metal group complained implant-related problems, and had their implants removed, and one in resorbable had an acute dehiscence, solved with surgical debridement and closure. At 6 and 9 months, the AOFAS score was applied for all patients. The functional results were similar in both groups. Implant removal was necessary in three patients from the metallic group. The resorbable plate provided qualitatively similar fracture healing results as the metal plate

Thesis--University of Oklahoma. / Bibliography: leaves 63-70.