口腔种植材料表面特性与生物膜形成研究进展

人类口腔环境为微生物提供了适宜生存的条件,多种微生物在牙齿表面形成了由基质包裹相互粘附的口腔生物膜,口腔生物膜是口腔微生物生存、代谢和致病的基础。随着1965年Brnemark种植体在临床上的成功应用,种植相关材料周围致病菌导致的种植体周围炎成为种植修复最常见的并发症之一,影响种植修复的远期效果。种植体周围炎引起了许多关注,并且口腔种植材料表面的特性和口腔生物膜的形成密切相关。本文就种植材料及天然牙齿表面的生物膜形成、种植材料表面特性对口腔生物膜及细菌粘附的影响因素、增强种植材料抗菌性能的方法以及未来的研究方向等作一综述。     

3D打印的医用材料在组织修复与治疗中的应用

当前由于交通和运动事故频发、骨肿瘤等疾病导致骨缺损、皮肤创伤不断加重等情况使病例日益增多，临床对修复材料的需求也逐年增加。不同临床修复材料的特性不同，而3D打印技术作为一项新型数字化成型技术，可与临床计算机断层扫描、磁共振成像等结合，利用计算机辅助设计个性化植入物，实现对孔隙结构的精准控制，设计出与患者受损区域几乎完全相同的三维多孔高活性修复材料，以实现精准医疗和个性化医疗。文章综述了近年来运用3D打印技术制备生物医用材料在组织修复与治疗方面的研究进展，包括生物材料的配方、制备原理及制备方法，并总结了3D生物打印技术的局限性和面临的挑战。     

对胶原基创面修复材料安全性评价的思考

近年来,胶原基创面修复类医疗器械产品的咨询和申报数量明显上升。本文对胶原基创面修复材料现状进行了介绍,并结合技术审评的情况,对其安全性的评价进行思考,以期对该类产品的申报注册有所帮助。     

胶原及其促创面修复作用的研究

本文介绍了牛胶原和猪真皮胶原制备方法、生物学特点以及动物移植的初步效果。结果表明胶原制备简便易行 ,氨基酸含量丰富 ,动物移植胶原材料效果肯定。提示胶原是创伤修复材料的理想天然生物资源     

修复与重建大面积胸壁缺损的临床研究进展

造成胸壁缺损的原因很多,但大面积胸壁缺损是胸外科不可忽视的一个重要问题,过大的胸壁缺损可导致患者气胸、胸壁软化、反常呼吸及纵膈摆动等,影响患者呼吸循环功能,必须修复重建。关于胸壁缺损的修复与重建手术技术已发展得较为成熟,对于术后影响较大的因素主要是对于不同胸壁缺损区域的选择手术方法及使用的修补材料的性质。本文就大面积胸壁缺损特点、原因、修复重建材料及技术应用的临床研究进展进行综述。     

四种口腔修复材料对细胞的毒性分析

目的:研究纯钛、钛合金、钴铬合金和镍铬合金四种非贵金属口腔修复材料对L-929成纤维细胞的毒性作用。方法:应用口腔修复材料制备材料浸提液处理培养L-929细胞,采用AnnexinV-FITC试剂盒比较细胞凋亡水平改变,采用Western blot检测细胞凋亡相关基因的表达。结果:纯钛与钛合金诱导L-929细胞凋亡的水平与对照组没有统计学差异(P>0.05);钴铬合金和镍铬合金材料浸提液可引起L-929细胞凋亡增加(P<0.05)。结论:纯钛与钛合金材料对口腔黏膜细胞的毒性作用相较钴铬合金和镍铬合金材料低,更具安全性。     

一种新型瓷嵌体修复用树脂粘接材料生物安全性评价

目的:初步评价一种新型瓷嵌体修复用树脂粘接材料的生物安全性。方法:按照国标GB16886.5-1997,医药行业标准YY/T0268-2001、YY/T0279-1995、以及YY/T 0244-1996所规定的方法对本院材料科新研制的复合树脂粘接材料的生物安全性进行评价,内容包括短期急性全身毒性试验,粘膜刺激实验,细胞毒性试验。结果:此种新型瓷嵌体修复用树脂粘接材料无细胞毒性,无短期全身毒性,对口腔黏膜无刺激。结论:此种新型瓷嵌体修复用树脂粘接材料具有良好的生物安全性,可以进行进一步安全性检测。     

应用3D适形打印制备网状复合体对兔颅骨缺损的修复作用及安全性研究

目的:探讨采用3D适形打印技术制备的羟基磷灰石/聚乳酸网状复合体在兔颅骨缺损中的修复作用及安全性。方法:以24只新西兰兔为研究对象,以羟基磷灰石/聚乳酸为材料,采用3D适形打印技术制备网状复合体,于兔颅骨顶部制成两个颅骨全层缺损,分别为孔A(左)和孔B(右),孔A(阳性对照组)以自体颅骨为修复材料,孔B(实验组)以复合体为修复材料,观察缺损修复区域的形态学、影像学(X线及CT扫描)及组织学检查结果。结果:植入后24周时,形态学显示:阳性对照组可见致密的骨组织修复,与缺损边缘界限不清,实验组中支架孔隙内纤维组织由新生骨质取代,且新生骨成熟度较提高,材料表面有部分吸收。CT扫描观察显示:冠状面上,阳性对照组缺损修复区域与周围正常骨组织融合为一体,实验组修复材料与缺损边缘融合紧密,与周围正常骨组织结合良好,部分边缘结合不连贯。组织学观察显示:实验组材料部分降解,材料间隔可见新生骨小梁。研究中无实验动物死亡,皮肤切口处缝合良好,无皮下积液,无移植物脱出、红肿感染等情况出现。结论:以3D适形打印技术制备的羟基磷灰石/聚乳酸复合体对兔颅骨缺损有较好的修复作用,能促进缺损区域新骨的形成和生长,且安全性较高。     

一种新型瓷嵌体修复用树脂粘接材料生物安全性评价

目的：初步评价一种新型瓷嵌体修复用树脂粘接材料的生物安全性。方法：按照国标GBl6886．5-1997,医药行业标准YY／T0268-2001、YY／T0279—1995、以及YY/T0244—1996所规定的方法对本院材料科新研制的复合树脂粘按材料的生物安全性进行评价,内容包括短期急性全身毒性试验,粘膜刺激实验,细胞毒性试验。结果：此种新型瓷嵌体修复用树脂粘接材料无细胞毒性,无短期全身毒性,对口腔黏膜无刺激。结论：此种新型瓷嵌体修复用树脂粘接材料具有良好的生物安全性,可以进行进一步安全性检测。     

可吸收材料在骨折内固定中的应用研究

骨折内固定常用的是金属材料,骨折愈合后再拆除,但金属材料有一定的副作用,其中最主要的是腐蚀和应力释放作用可引起皮质骨疏松和再骨折。可吸收材料的崛起是骨折内固定的一大进展。 可吸收材料的研究进展 采用可吸收材料修复骨组织的历史应追溯到60年代末期,在整个70年代这方面的研究报道还不多。其中应用最早的是颌面外科,     

骨生物材料通过细胞途径降解的研究进展

生物材料作为移植物已广泛应用于骨组织修复,在应用生物材料时需要考虑材料各个方面的性能,如生物兼容性、力学强度、可塑性等。材料的可降解性也是骨修复材料不得不考虑的方面。既往研究表明,生物材料可以通过物理、化学和生物三种方式进行降解。在材料的生物降解过程中,经细胞途径降解是其中重要的一环。这种降解途径主要是通过巨噬细胞、破骨细胞的生物学行为及其所分泌的生物活性氧、酶、酸性代谢物等作用机制进行。认识细胞作用对生物材料的降解有助于更好地理解细胞的生物学行为,精准设计、制造更合理的骨修复材料,既利于材料植入时的初始稳定,也可以符合材料降解与新骨形成的匹配,促进骨再生和骨修复。     

植入了骨修复材料的小型猪腰椎椎体不脱钙病理组织切片制备方法

摘要 目的：建立植入了骨修复材料小型猪腰椎椎体骨组织标本的不脱钙病理组织切片制备方法。方法：将含骨修复材料的腰椎椎体骨组织标本进行分割暴露组织切面,梯度浓度乙醇脱水后经Technovit 7200 VLC光聚树脂浸润,经黄蓝光共同辐照进行光聚合包埋,借助硬组织病理切磨系统制备含骨修复材料不脱钙病理组织切片。结果：结果显示通过上述方法制备的病理组织切片,经苏木精-伊红（HE）染色及甲苯胺蓝染色后光学显微镜下观察能较好地显示骨的各种组织细胞结构,可清晰的观察到骨小梁的走向及连接情况。结论：研究建立了含骨修复材料骨组织标本病理组织切片制备方法,实现了含骨修复材料不脱钙骨组织病理切片的制备,经病理染色后实现了带植入物的组织学观察,为生物材料及医疗器械动物试验研究提供了新的病理检测手段及组织学评价途径。     

Site specific effects of zoledronic acid during tibial and mandibular fracture repair

Numerous factors can affect skeletal regeneration, including the extent of bone injury, mechanical loading, inflammation and exogenous molecules. Bisphosphonates are anticatabolic agents that have been widely used to treat a variety of metabolic bone diseases. Zoledronate (ZA), a nitrogen-containing bisphosphonate (N-BP), is the most potent bisphosphonate among the clinically approved bisphosphonates. Cases of bisphosphonate-induced osteonecrosis of the jaw have been reported in patients receiving long term N-BP treatment. Yet, osteonecrosis does not occur in long bones. The aim of this study was to compare the effects of zoledronate on long bone and cranial bone regeneration using a previously established model of non-stabilized tibial fractures and a new model of mandibular fracture repair. Contrary to tibial fractures, which heal mainly through endochondral ossification, mandibular fractures healed via endochondral and intramembranous ossification with a lesser degree of endochondral ossification compared to tibial fractures. In the tibia, ZA reduced callus and cartilage formation during the early stages of repair. In parallel, we found a delay in cartilage hypertrophy and a decrease in angiogenesis during the soft callus phase of repair. During later stages of repair, ZA delayed callus, cartilage and bone remodeling. In the mandible, ZA delayed callus, cartilage and bone remodeling in correlation with a decrease in osteoclast number during the soft and hard callus phases of repair. These results reveal a more profound impact of ZA on cartilage and bone remodeling in the mandible compared to the tibia. This may predispose mandible bone to adverse effects of ZA in disease conditions. These results also imply that therapeutic effects of ZA may need to be optimized using time and dose-specific treatments in cranial versus long bones.     

Mepe is expressed during skeletal development and regeneration

Matrix extracellular phosphoglycoprotein (Mepe) is a bone metabolism regulator that is expressed by osteocytes in normal adult bone. Here, we used an immunohistochemical approach to study whether Mepe has a role in murine long bone development and regeneration. Our data showed that Mepe protein was produced by osteoblasts and osteocytes during skeletogenesis, as early as 2 days postnatal. During the healing of non-stabilized tibial fractures, which occurs through endochondral ossification, Mepe expression was first detected in fibroblast-like cells within the callus by 6 days postfracture. By 10 and 14 days postfracture (the hard callus phase of repair), Mepe was expressed within late hypertrophic chondrocytes and osteocytes in the regenerating tissues. Mepe became externalized in osteocyte lacunae during this period. By 28 days postfracture (the remodeling phase of repair), Mepe continued to be robustly expressed in osteocytes of the regenerating bone. We compared the Mepe expression profile with that of alkaline phosphatase, a marker of bone mineralization. We found that both Mepe and alkaline phosphatase increased during the hard callus phase of repair. In the remodeling phase of repair, Mepe expression levels remained high while alkaline phosphatase activity decreased. We also examined Mepe expression during cortical bone defect healing, which occurs through intramembranous ossification. Mepe immunostaining was found within fibroblast-like cells, osteoblasts, and osteocytes in the regenerating bone, through 5 to 21 days postsurgery. Thus, Mepe appears to play a role in both long bone regeneration and the latter stages of skeletogenesis.     

Designs from the deep: marine organisms for bone tissue engineering

Current strategies for bone repair have accepted limitations and the search for synthetic graft materials or for scaffolds that will support ex vivo bone tissue engineering continues. Biomimetic strategies have led to the investigation of naturally occurring porous structures as templates for bone growth. The marine environment is rich in mineralizing organisms with porous structures, some of which are currently being used as bone graft materials and others that are in early stages of development. This review describes the current evidence available for these organisms, considers the relative promise of each and suggests potential future directions.     

Microstructures of External Periosteal Callus of Repaired Femoral Fracture in Children

In order to understand further the mechanism of bone fracture repair, and thus to innovate better operative treatment for bone fracture and to design new implant materials for bone repair, microstructures of external periosteal callus (EPC) of repaired femoral fracture in both children and adults were investigated by using a scanning electron microscope, transmission electron microscopy, and an X-ray microdiffractometer. The repair time after the fractures in children and adults is on average 155 and 370 days, respectively. Collagen fibrils making up children's EPC (CEPC) are underdeveloped and insufficiently mineralized by hydroxyapatite (HA), while those from adults' EPC (AEPC) are similar to normal bone. A lot of particles loaded by brushite (DCPD) minerals were found among the collagen fibrils of CEPC. The main mineral phases in CEPC consist of DCPD and HA, while only HA exists in AEPC. Deposition of DCPD minerals could have compensated for the insufficient mineralization of the collagen fibrils of CEPC, thereby making fractured bone repair more rapidly in children than in adults.     

Natural and artificial chitosan-inorganic composites

Taking inspiration from many chitin-inorganic composites in nature, a number of recent articles throw light on the manufacture of such composites based on calcium carbonate, calcium phosphate and silica. These novel materials are important in the field of blood-compatible materials, bone substitutes, and cements for bone repair and reconstruction. This approach provides an attractive alternative to the processing of inorganic thin films, especially in applications where substrates cannot be exposed to high temperatures.     

Sequential In vivo Imaging of Osteogenic Stem/Progenitor Cells During Fracture Repair

Bone turns over continuously and is highly regenerative following injury. Osteogenic stem/progenitor cells have long been hypothesized to exist, but in vivo demonstration of such cells has only recently been attained. Here, in vivo imaging techniques to investigate the role of endogenous osteogenic stem/progenitor cells (OSPCs) and their progeny in bone repair are provided. Using osteo-lineage cell tracing models and intravital imaging of induced microfractures in calvarial bone, OSPCs can be directly observed during the first few days after injury, in which critical events in the early repair process occur. Injury sites can be sequentially imaged revealing that OSPCs relocate to the injury, increase in number and differentiate into bone forming osteoblasts. These methods offer a means of investigating the role of stem cell-intrinsic and extrinsic molecular regulators for bone regeneration and repair.     

Role of matrix metalloproteinase 13 in both endochondral and intramembranous ossification during skeletal regeneration

Extracellular matrix (ECM) remodeling is important during bone development and repair. Because matrix metalloproteinase 13 (MMP13, collagenase-3) plays a role in long bone development, we have examined its role during adult skeletal repair. In this study we find that MMP13 is expressed by hypertrophic chondrocytes and osteoblasts in the fracture callus. We demonstrate that MMP13 is required for proper resorption of hypertrophic cartilage and for normal bone remodeling during non-stabilized fracture healing, which occurs via endochondral ossification. However, no difference in callus strength was detected in the absence of MMP13. Transplant of wild-type bone marrow, which reconstitutes cells only of the hematopoietic lineage, did not rescue the endochondral repair defect, indicating that impaired healing in Mmp13-/- mice is intrinsic to cartilage and bone. Mmp13-/- mice also exhibited altered bone remodeling during healing of stabilized fractures and cortical defects via intramembranous ossification. This indicates that the bone phenotype occurs independently from the cartilage phenotype. Taken together, our findings demonstrate that MMP13 is involved in normal remodeling of bone and cartilage during adult skeletal repair, and that MMP13 may act directly in the initial stages of ECM degradation in these tissues prior to invasion of blood vessels and osteoclasts.     

Bone regeneration and stem cells

This invited review covers research areas of central importance for orthopaedic and maxillofacial bone tissue repair, including normal fracture healing and healing problems, biomaterial scaffolds for tissue engineering, mesenchymal and foetal stem cells, effects of sex steroids on mesenchymal stem cells, use of platelet-rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed.