纤维结合蛋白及其在创伤修复中的作用

纤维结合蛋白及其在创伤修复中的作用李秀兰师宜健陆静天津骨科研究所（天津３００２１１）纤维结合蛋白（ｆｉｂｒｏｎｅｃｔｉＦＮ）一词源于拉丁词干ｆｉｂｒａ和ｎｅｃｔｅｒｅ，反映了这类蛋白质最明显的作用。ＦＮ是１９４８年Ｍｏｒｒｉｓｏｎ最先报道，近十余年，...     

膜引导性组织再生修复骨缺损研究——膜材料的研究与应用

膜引导性组织再生修复骨缺损研究膜材料的研究与应用李秀兰郭洪刚师宜健天津市天津医院（天津３００２１１）膜引导性组织再生（ｍｅｍｂｒａｎｅｇｕｉｄｅｄｔｉｓｓｕｅｒｅ－ｇｅｎｅｒａｔｉｏｎ，ＭＧＴＲ）技术是一种新型促骨再生技术［１，２］。这种技术是利用膜...     

云南白药促进骨缺损修复及引导性骨再生的实验研究

目的：阐明云南白药促进骨缺损修复及引导性骨再生的愈合机制，为临床上治疗骨折提供理论依据。方法：36只新西兰兔制作桡骨缺损不愈合模型和引导性骨再生模型，随机均分用药组及对照组，手术后3d、1、3、5、10、12周取材，观察骨痂愈合程度的差异及骨痂组织学变化，结果：实验组有明显的促进骨缺损修复作用，并在引导性骨再生中的膜内成骨作用强于对照组，结论：云南白药对骨缺损修复及引导性骨再生有明显的促进作用。     

聚乳酸膜管在引导性骨再生中的实验观察

目的：膜管的应用是引导性骨再生过程的关键。可吸收，组织相容性好的膜材料是发展的方向。探讨聚乳酸膜管在引导性骨再生中应用的可能性。方法３０只成年新西兰大白兔，实验侧断端用聚乳酸膜管包裹，另一侧不作处理作为对照组。术后１、３、６、９、１２周分别处死动物，标本行Ｘ线、组织学检查，结果对照组无一例骨缺损修复，骨断端间被增生的纤维缔组织所占据。而实验侧新生骨在９、１２周时沿膜管内层连接两断端。聚乳酸膜管具有     

骨形态发生蛋白在骨缺损修复研究中的应用现状

骨缺损是骨科治疗中的一个难题 ,骨形态发生蛋白 (ｂｏｎｅｍｏｒｐｈｏｇｅｎｅｔｉｃｐｒｏｔｅｉｎ,ＢＭＰ)具有较强的诱导成骨能力 ,是目前治疗骨缺损、骨折不愈合常用的新材料和方法。国内外在这方面作了大量研究和应用 ,现综述如下 :1　ＢＭＰ的生物学特性ＢＭＰ是 1 965年Ｕｒｉｓｔ发现的[1 ] 一种存在于骨基质中的糖蛋白多肽 ,含有二硫键结构 ,分子量 1 8～ 30ＫＤ ,ＰＩ为 5 .0±0 .2。其来源于骨及骨源细胞 ,是骨代谢的旁分泌物 ,也是特异性的骨生长因子 ,它的靶细胞为血管周围具有潜在分化能力的间充质细胞。ＢＭＰ与靶细胞膜上…     

膜引导组织再生技术在骨缺损治疗中的应用

膜引导性组织再生是利用膜技术阻挡周围组织长入缺损处，为缺损愈合创造理想环境，从而达到促进组织愈合的目的，目前已处在临床应用阶段。近年来膜引导性组织再生在长管骨、颅面骨和种植体等方面的研究已取得了重大进展，对其机理也有了较深的认识。     

纤维结合蛋白在伤口愈合中的作用

纤维结合蛋白(fibronectin.FN)是广泛存在于机体组织中的重要糖蛋白,它可以与纤维原、纤维蛋白原、肝素及硫酸肝素和胶原相结合,也可以通过位于细胞表面的 FN 受体与细胞和血小板等相结合。由于 FN 具有上述功能,它在伤口的修复和愈合过程中担着十分重要的作用:1)作为趋化因子(chemotaxis)诱导外周血中的单核细胞及其它吞噬细胞、上皮细胞、成纤维细胞向伤口处运动。2)作为一种非特异调理素(opsone)调动吞噬系统清除病菌及组织碎片、净化伤口。3)作为细胞运动的基质。4)作为基质形成的基础。5)作为生长因子,具有强烈的促细胞生长活性。     

异种骨复合异种骨形态发生蛋白在肿瘤性骨缺损修复的应用

异种骨复合异种骨形态发生蛋白在肿瘤性骨缺损修复的应用侯树勋，吴闻文，姚长海，杨连甲骨形态发生蛋白（ＢｏｎｅＭｏｒｐｈｏｇｅｎｅｔｉｃｐｒｏｔｅｉｎ，ＢＭＰ）是一种自骨组织中提取的酸性多肽氨基酸复合物，具有诱导未分化问质细胞，分化成软骨细胞和骨细胞的作...     

纤维结合蛋白与肾脏病

1948年,Morrlson等人前先从正常人的血浆中分离出一种不溶性冷球蛋白,它不同于纤维蛋白原,经凝血酶处理后,不能使其凝固。以后,人们对此蛋白进行了大量的研究,发现这种蛋白广泛存在于体液和细胞外基质,在免疫、血凝及血小板凝集等方面具有生物活性。此蛋白的命名比较混乱,曾称为可溶性成纤维细胞抗原、细胞表面蛋白、细胞粘附因子和调理蛋白等。直到70年代,人们才广泛应用纤维结合蛋白(Fibronectin,FN)的名称。自从1978年,Scheinman首次描述FN在肾小球内的定位以来,许多学者对FN在各种肾小球肾炎的肾组织分布以及血浆FN(P-FN)浓度的变化进行了观察,本文就这方面的研究近况作一介绍。一、FN的生物特性     

组织工程化同种异体骨移植修复骨缺损

目的解决骨缺损修复时自体骨移植存在修复材料来源有限,异体骨移植又为爬行替代,存在愈合慢、假关节率高的问题。方法以兔骨膜成骨细胞为种子细胞,经分离、体外培养、传代,再粘附于冷冻干燥表面脱钙同种异体骨,共同复合培养,制作兔胫骨缺损,分异体骨移植组(对照组)、组织工程化异体骨移植组,术后2、4、6周各处死2只兔子,大体观测骨痂大小及硬度;苏木精-伊红染色,光镜观察细胞在材料上的生长情况,了解其愈合快慢及质量。结果与对照组比较,实验组炎性明显较轻,细胞生长活跃,缺损愈合快。结论组织工程化同种异体骨移植能解决骨缺损修复时自体植骨材料来源有限,特别是在小儿及骨缺损大时修复材料的来源问题;同时,植入的异体骨又具有支架及自体成骨细胞活性,使植入的异体骨愈合加快,克服其愈合慢、假关节率高的问题。     

组织工程骨修复骨缺损的研究进展

复习相关文献,综合性报道种子细胞、生物材料及组织工程骨替代被修复重建组织的研究,指出目前存在的问题和今后研究的方向。     

A Bioactive Coating Enhances Bone Allografts in Rat Models of Bone Formation and Critical Defect Repair

Bone allografts are inferior to autografts for the repair of critical‐sized defects. Prior studies have suggested that bone morphogenetic protein‐2 (BMP‐2) can be combined with allografts to produce superior healing. We created a bioactive coating on bone allografts using polycondensed deoxyribose isobutyrate ester (PDIB) polymer to deliver BMP‐2 ± the bisphosphonate zoledronic acid (ZA) and tested its ability to enhance the functional utility of allografts in preclinical Wistar rat models. One ex vivo and two in vivo proof‐of‐concept studies were performed. First, PDIB was shown to be able to coat bone grafts (BGs). Second, PDIB was used to coat structural allogenic corticocancellous BG with BMP‐2 ± ZA ± hydroxyapatite (HA) microparticles and compared with PDIB‐coated grafts in a rat muscle pouch model. Next, a rat critical defect model was performed with treatment groups including (i) empty defect, (ii) BG, (iii) collagen sponge + BMP‐2, (iv) BG + PDIB/BMP‐2, and (v) BG + PDIB/BMP‐2/ZA. Key outcome measures included detection of fluorescent bone labels, microcomputed tomography (CT) quantification of bone, and radiographic healing. In the muscle pouch study, BMP‐2 did not increase net bone volume measured by microCT, however, fluorescent labeling showed large amounts of new bone. Addition of ZA increased BV by sevenfold (p < 0.01). In the critical defect model, allografts were insufficient to promote reliable union, however, union was achieved in collagen/BMP‐2 and all BG/BMP‐2 groups. Statement of clinical significance: These data support the concept that PDIB is a viable delivery method for BMP‐2 and ZA delivery to enhance the bone forming potential of allografts. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2278–2286, 2019     

复合骨形态发生蛋白胎儿骨修复长骨缺损的实验研究

寻找满意的骨形态发生蛋白（ＢＭＰ）的载体一直是应用ＢＭＰ修复骨缺损研究中的一个重要课题，为探讨胎儿骨（ＦＢ）能否成为ＢＭＰ载体，制备了复合ＢＭＰ胎儿骨（ＢＭＰ／ＦＢ），将其植入兔桡骨中段１５ｍｍ人工缺损处，以单纯ＦＢ植入、异体骨（ＡＬＢ）植入、空白作为对照，通过Ｘ线摄片，光镜观察，电子探针钙磷元素测定等方法了解各组骨缺损修复速度和愈合程度。结果发现ＢＭＰ／ＦＢ植入侧４周时骨缺损处有大量间充质细胞聚集，８周形成骨小梁，ＦＢ基本被吸收，１２周出现部分板层骨，钙磷值达到正常桡骨皮质骨水平，１６周骨细胞成熟，髓腔再通，外观塑形较好，在不同时间点骨缺损修复程度，ＢＭＰ／ＦＢ组明显优于ＦＢ组，ＦＢ组优于ＡＬＢ组，空白组骨缺损则被纤维组织，脂肪组织等填充。实验证明ＦＢ是一种良好的ＢＭＰ载体。     

聚磷酸钙纤维/磷酸钙骨水泥/微小颗粒骨修复骨缺损的实验研究

目的探讨聚磷酸钙纤维(calcium polyphosphate fibers,CPPF)、磷酸钙骨水泥(calcium phosphate cement,CPC)、自体微小颗粒骨复合材料修复骨缺损的能力。方法选用新西兰大白兔72只,双侧桡骨制成1.5cm骨缺损模型,随机分成6组分别植入。A组:CPPF/CPC/微小颗粒骨复合材料;B组:CPC/微小颗粒骨复合材料;C组:单纯微小颗粒骨;D组:CPPF/CPC复合材料;E组:单纯CPC;F组:空白对照组,不植入任何物质。在2、4、8、12周各时相点,分别进行大体观察、X线照片、组织学切片、扫描电镜观察及力学测试。结果A组在12周可使骨缺损修复,在骨缺损修复各时期,其成骨速度及成骨量均好于其他各组。结论CPPF/CPC/微小颗粒骨复合材料有良好的成骨能力、力学特性和生物相容性,有望成为骨组织工程中修复骨缺损的理想材料。     

bBMP-胶原-珊瑚复合人工骨修复桡骨干骨缺损的实验研究

目的评价牛骨形态发生蛋白(bBMP)-胶原-珊瑚复合人工骨对长骨干骨缺损的修复效果.方法建立46只兔双侧桡骨干骨缺损模型,分为4组1.人工骨组(18侧)、2.自体骨组(16侧)、3.单纯珊瑚组(12侧)、4.对照组(为以上各组的左侧,未治疗).于4周及16周末分别行X线、病理学、ALP活性、四环素荧光标记及生物力学检查.结果4周,人工骨组组织中的ALP活性高于对照组.16周,1、2、3、4组的愈合率,分别为75%(9/12)、100%(10/10)、28.6%(2/7)、31.0%(9/29).与3组及4组相比,1组及2组的荧光带较宽,桡骨的抗弯强度较高.结论复合人工骨有较强的修复长骨干骨缺损的能力,有望成为自体骨的替代品.     

Subchondral Bone Reaction Associated with Chondral Defect and Attempted Cartilage Repair in Goats

Repair of cartilage damage with autologous chondrocyte transplantation (ACT) has become popular in clinical use during the past few years. Although clinical results have mostly been successful, several unanswered questions remain regarding the biological mechanism of the repair process. The aim of this study was to develop a goat model for ACT. The repair was not successful due to the graft delamination, but we characterize the subchondral changes seen after the procedure. A chondral lesion was created in 14 goat knees, operated on 1 month later with ACT, and covered with periosteum or a bioabsorbable poly-L/D-lactide scaffold. After 3 months, only two of the five lesions repaired with ACT showed partly hyaline-like repair tissue, and all lesions (n = 4) with the scaffold failed. Even though the lesions did not extend through the calcified cartilage, the bone volume and collagen organization of bone structure were decreased when assessed by quantitative polarized light microscopy. There was a significant loss of bone matrix and distortion of the trabecular structure of subchondral bone, which extended several millimeters into the bone. The subchondral bone demonstrated strong hyaluronan staining in the bone marrow and cartilaginous areas with signs of endochondral ossification, suggesting structural remodeling of the bone. The goat model used here proved not to be an optimal model for ACT. The changes in subchondral bone may alter the biomechanical properties of the subchondral plate and thus the long-term survival of the repair tissue after ACT.     

低频振动刺激BMSCs修复骨缺损在体实验研究

目的 通过在体试验,探讨以骨髓基质干细胞(BMSCs)为种子细胞种植于脱钙骨支架与低频振动相结合进行修复骨缺损的可行性.方法 对30只家兔随机分为三组,A组:植入脱钙骨,B、C组:植入脱钙骨复合BMSCs.A、B两组施加频率25HZ振动,C组不参加振动,第5周取标本观测骨缺损愈合情况.结果 通过大体标本,组织学,电镜及...     

Subchondral Bone Reaction Associated with Chondral Defect and Attempted Cartilage Repair in Goats

Repair of cartilage damage with autologous chondrocyte transplantation (ACT) has become popular in clinical use during the past few years. Although clinical results have mostly been successful, several unanswered questions remain regarding the biological mechanism of the repair process. The aim of this study was to develop a goat model for ACT. The repair was not successful due to the graft delamination, but we characterize the subchondral changes seen after the procedure. A chondral lesion was created in 14 goat knees, operated on 1 month later with ACT, and covered with periosteum or a bioabsorbable poly-L/D-lactide scaffold. After 3 months, only two of the five lesions repaired with ACT showed partly hyaline-like repair tissue, and all lesions (n = 4) with the scaffold failed. Even though the lesions did not extend through the calcified cartilage, the bone volume and collagen organization of bone structure were decreased when assessed by quantitative polarized light microscopy. There was a significant loss of bone matrix and distortion of the trabecular structure of subchondral bone, which extended several millimeters into the bone. The subchondral bone demonstrated strong hyaluronan staining in the bone marrow and cartilaginous areas with signs of endochondral ossification, suggesting structural remodeling of the bone. The goat model used here proved not to be an optimal model for ACT. The changes in subchondral bone may alter the biomechanical properties of the subchondral plate and thus the long-term survival of the repair tissue after ACT.     

Spatiotemporal Analyses of Osteogenesis and Angiogenesis via Intravital Imaging in Cranial Bone Defect Repair

Osteogenesis and angiogenesis are two integrated components in bone repair and regeneration. A deeper understanding of osteogenesis and angiogenesis has been hampered by technical difficulties of analyzing bone and neovasculature simultaneously in spatiotemporal scales and in 3D formats. To overcome these barriers, a cranial defect window chamber model was established that enabled high‐resolution, longitudinal, and real‐time tracking of angiogenesis and bone defect healing via multiphoton laser scanning microscopy (MPLSM). By simultaneously probing new bone matrix via second harmonic generation (SHG), neovascular networks via intravenous perfusion of fluorophore, and osteoblast differentiation via 2.3‐kb collagen type I promoter‐driven GFP (Col2.3GFP), we examined the morphogenetic sequence of cranial bone defect healing and further established the spatiotemporal analyses of osteogenesis and angiogenesis coupling in repair and regeneration. We showed that bone defect closure was initiated in the residual bone around the edge of the defect. The expansion and migration of osteoprogenitors into the bone defect occurred during the first 3 weeks of healing, coupled with vigorous microvessel angiogenesis at the leading edge of the defect. Subsequent bone repair was marked by matrix deposition and active vascular network remodeling within new bone. Implantation of bone marrow stromal cells (BMSCs) isolated from Col2.3GFP mice further showed that donor‐dependent bone formation occurred rapidly within the first 3 weeks of implantation, in concert with early angiogenesis. The subsequent bone wound closure was largely host‐dependent, associated with localized modest induction of angiogenesis. The establishment of a live imaging platform via cranial window provides a unique tool to understand osteogenesis and angiogenesis in repair and regeneration, enabling further elucidation of the spatiotemporal regulatory mechanisms of osteoprogenitor cell interactions with host bone healing microenvironment. © 2015 American Society for Bone and Mineral Research.