自体骨、同种异体骨及骨形态发生蛋白重组骨治疗腰椎骨折

背景：骨形态发生蛋白重组骨是一种新型植骨材料,已逐步应用于临床,但在腰椎骨折植骨融合中效果仍少见报道。 目的：比较自体骨、同种异体骨及骨形态发生蛋白重组骨治疗腰椎骨折的疗效差异。 方法：选择2005年3月至2009年3月南阳医学高等专科学校附属第一医院收治的腰椎骨折患者78例,根据植骨材料不同随机分为3组,分别植入自体骨、同种异体骨、骨形态发生蛋白重组骨。 结果与结论：78例腰椎骨折患者均获24个月的随访。植骨后24个月JOA评分改善率骨形态发生蛋白植入组90%>自体骨植入组85%>同种异体骨植入组70%(P < 0.05);植骨后12,24个月,同种异体骨植入组Cobb角较其他2组和植骨后6个月增大(P < 0.05),较植骨前减小(P < 0.05);自体骨植入组与骨形态发生蛋白植入组相比,差异无统计学意义(P > 0.05);同种异体骨植入组植骨后各时间点骨融合率均低于其他2组(P < 0.05)。提示骨形态发生蛋白重组骨与自体骨应用于脊椎腰椎骨折近期疗效相似,均优于同种异体骨移植,骨形态发生蛋白重组骨在腰椎骨折脊柱融合快,效果更好,临床应用更有优势。     

骨组织工程支架材料--陶瓷化骨

陶瓷化骨作为骨移植材料 ,得到广泛的研究 ,并已应用于临床。由于其具有天然的骨小梁结构 ,可降解 ,无免疫原性 ,是骨组织工程比较理想的支架材料 ,因此越来越受到重视。本文主要综述陶瓷化骨的理化性质、生物学特性及在骨组织工程中的应用     

纳米脱钙骨基质促进骨愈合

背景：纳米脱钙骨基质具有较大的表面积/体积比,纳米颗粒团聚后在表面自然形成不规则的纳米沟槽,可促进成骨细胞在其表面黏附生长及基质分泌。 目的：评价纳米脱钙骨基质作为骨移植替代物的植骨融合能力。 方法：以改良Urist法制备人同种异体脱钙骨基质,使用液氮冷冻球磨机及MICROS超细粉碎机制备纳米脱钙骨基质。咬除家兔L2-4双侧小关节及双侧椎板和横突表面皮质骨,随机分为3组,分别在腰椎椎板及横突间植入纳米脱钙骨基质、脱钙骨基质及自体骨,术后4,8,12周通过影像学、组织学观察植骨融合效果。 结果与结论：①X射线与CT表现：术后12周,纳米脱钙骨基质组椎板、附件形态已接近正常节段,新生骨与椎板间隙完全消失,新生骨与植骨床骨质密度均匀一致;脱钙骨基质组植骨区域椎板表面有少量新生骨块影,在新生骨与椎板表面尚有一定间隙;自体骨组椎板与植骨融合界面愈合良好,植骨区有新生骨块影,融合骨块质地均匀。②组织学表现：术后12周,纳米脱钙骨基质被新生骨替代,与椎板间形成骨性连接,新生骨内可见大量骨细胞,与自体骨组效果相似;脱钙骨基质组植骨区达到骨性愈合,新生骨内可见板层样骨,也有类骨物质。表明纳米脱钙骨基质具有良好的成骨诱导能力,是自体骨移植的良好替代物。     

Replacement of bone marrow by bone in rat femurs: the bone bioreactor

During development and repair of bone, two distinct yet complementary mechanisms, intramembranous and endochondral, mediate new bone formation via osteoblasts. Because mechanical bone marrow ablation leads to the rapid and transient formation of new bone in the marrow cavity, we postulated that parathyroid hormone (PTH), which is a bone anabolic hormone, enhances the formation of new bone that forms after marrow ablation. We subjected the left femur of rats to mechanical marrow ablation, or sham operation, and injected the animals daily with PTH or vehicle for 1, 2, or 3 weeks in a first experiment, then with PTH, parathyroid hormone-related peptide (PTHrP), or vehicle for 3 weeks in a second experiment. We subjected both femurs from each rat to soft X-ray, peripheral quantitative computed tomography, computed tomography on a microscale, and histological analysis, and determined the concentration of serum osteocalcin. In addition, in the second experiment, we determined the serum concentration of calcium, tartrate-resistant acid phosphatase (TRAP), and receptor activator of NF-kappaB ligand (RANKL) at 3 weeks, and subjected femurs to biomechanical testing. Following treatment with PTH or PTHrP for 3 weeks, bone filled the marrow cavity of the shafts whose marrow had been ablated. PTH increased trabecular density in the right femur, but failed to induce bone formation in the medullary region of the right unoperated femoral shafts. The newly formed bone endowed left femoral shafts with improved biomechanical properties when compared to those of right femurs and left femurs from control, sham-operated, and vehicle-treated rats. PTHrP, like PTH, increased serum osteocalcin, but neither increased serum calcium, TRAP, or RANKL at 3 weeks. Our results reveal that the newly formed bone that follows marrow ablation is responsive to PTH, expand the role of PTH in bone, and might open new avenues of investigations to the field of regenerative medicine and tissue engineering. Local bone marrow removal in conjunction with pharmacologic intervention with an anabolic agent might provide a technique for rapid preferential site-directed bone growth in areas of high bone loss.     

Bioactive glass and autogenous bone as bone graft substitutes in benign bone tumors

In a prospective randomized study, 25 patients with benign bone tumors were surgically treated with either bioactive glass S53P4 (BG) or autogenous bone (AB) as bone graft material. X-rays were taken preoperatively and postoperatively at 2 weeks and at 3, 8, 12, 18, 24, and 36 months. In addition, for most of the patients, CT scans were performed at the same time-points. No infections or material-related adverse reactions occurred in any patient. The filled cavity was replaced faster by new bone in the AB group than in the BG group (p = 0.0001). However, at 36 months, no statistical difference in cavity volume between the two groups was observed on X-rays (p = 0.7881) or on CT scans (p = 0.9117). In the BG group at 3 years, the filled cavity appeared, however, dense on X-rays, and glass granules on CT scans were observed. During the follow-up period, the cortical thickness seemed to increase more in the BG group than in the AB group (p < 0.0001).     

自体骨及重组人骨形态发生蛋白2复合骨在腰椎中融合的效果：与异体骨比较

BACKGROUND: Recombinant human bone morphogenetic protein 2 (rhBMP2) can effectively promote new  bone formation and fracture healing, but its specific application in the lumbar spinal fusion remains controversial. OBJECTIVE: To study the effect of autogenous bone, rhBMP2 composite bone or allogeneic bone on the lumbar spinal fusion of rabbits.  METHODS: Forty-five New Zealand white rabbits were enrolled to make intertransverse lumbar interbody fusion models and then randomly subjected to autogenous iliac bone, rhBMP2 composite bone or allogeneic iliac bone via L5-L6 intertransverse process, respectively. Then, the rats were sacrificed under anesthesia at 8 weeks after operation to observe the lumbar fusion. RESULTS AND CONCLUSION: Compared with the allogeneic iliac bone group, the fusion rates, tensile strength ratio of L5-6/L4-5, and percentage of new bone tissues were increased more significantly in the other two groups  (P < 0.05), and moreover, there was no difference between the autogenous iliac bone and rhBMP2 composite bone groups. These findings indicate that the autogenous iliac bone and rhBMP2 composite bone have similar fusion effects, both of which are superior to the allogeneic bone.   中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

自体骨髓移植复合人工骨治疗骨缺损

背景：到目前为止,国内人工骨联合自体骨髓移植治疗新鲜骨折、骨缺损方面的基础与临床研究尚未见报道。 目的：分析自体骨髓移植复合人工骨修复四肢粉碎性骨折骨缺损的作用途径。 方法：42例四肢骨缺损患者按治疗方法分为3组,均采用内固定方法修复骨折骨缺损。复合组采用自体骨髓移植复合人工骨,人工骨移植组仅作单纯的人工骨移植,自体骨髓移植组仅将单纯的自体骨髓注射入骨缺损处。所有患者均行骨特异性碱性磷酸酶活性检测和影像学随访,观察骨痂形成及骨折愈合情况。 结果与结论：在内固定后第3,4,6周,复合组伤肢骨痂形成率、骨特异性碱性磷酸酶活性均显著高于人工骨移植组及自体骨髓移植组(P < 0.01)。提示自体骨髓移植复合人工骨较单纯的人工骨移植或自体骨髓移植更能促进早期骨痂反应,加速骨折后骨缺损愈合,缩短骨愈合时间及住院时间。     

骨水泥成形术治疗骨转移瘤的临床观察

目的 观察应用微创技术治疗骨转移瘤引起疼痛的效果.方法 17例骨转移患者,59处骨转移病灶(55处在椎体,3处在四肢骨,1处在骨盆),其中男性5例,女性12例,年龄30～78岁,平均年龄58.9岁,影像学检查均证实有骨转移瘤(X线片、CT及MRI).临床伴有明显持续性骨痛,症状持续时间为2～18个月,平均5.7个月.17例患者59处骨转移灶均给予骨水泥成形术治疗.观察治疗前后患者的疼痛强度的变化情况、镇痛药使用评分并行SF-12健康状况调查.结果 17例59处病灶手术顺利完成.患者的疼痛评分由治疗前的5.0～9.5(平均7.9±1.2)减少为治疗后的3.1～6.8(平均5.1±1.0)(P＜0.01).患者的止痛药使用评分由治疗前的3～4(平均3.6±0.6),减少为治疗后的1～3(平均2.4±1.1)(P＜0.01).SF-12健康调查评分治疗前为-17～-33,平均-30.00±4.03,治疗后为-18～-33,平均-26.00±3.94(P＜0.05).术后随访6～17个月,平均12.3个月,患者疼痛均较术前减轻,17例患者中1例在治疗期间出现1个椎体新发的压缩性骨折.结论 应用骨水泥成形术治疗骨转移瘤可有效地缓解疼痛,改善患者后期生活质量.     

Pseudotumors of bone and bone lesions mimicking tumours

We review entities that have historically been thought to be pseudotumors or mimics of bone tumours. We discuss tumifactive amyloid deposits, the brown tumours of hyperparathyroidism, the various types of cysts that can be seen in bone, Nora lesion, subungual exostosis, haemophilic pseudotumors, non-ossifying fibroma, fibrous dysplasia, osteofibrous dysplasia, Paget disease, tophaceous gout and pseudogout.     

生物衍生骨在骨组织工程研究中的应用

支架材料的选取是骨组织工程研究的关键 ,生物衍生骨具有较好的生物相容性和材料界面 ,三维立体孔隙 -网架合理 ,可塑性强 ,可降解 ,并具备一定的力学强度 ,兼备良好的骨传导及一定的骨诱导能力。可作为种子细胞的支架材料应用于骨组织工程研究。     

Harvest of human bone marrow directly from bone

Harvest of human bone marrow directly from freshly resected bone provides purer preparations of marrow than can be obtained by the conventional technique of multiple aspirations from the iliac crests. In particular, directly harvested marrow is much less heavily contaminated with peripheral blood lymphocytes, a known source of mature T cells. Because of the possible relevance of these contaminating T cells for cadaveric bone marrow transplants, the best source of human marrow harvested directly from bone has been studied. Human bone marrow was harvested from 46 surgical specimens and 9 cadaveric tissue donors. Vertebral bodies provided the best source of bone marrow with average yields of 3.1 ± 1.6 × 10⁹ cells per vertebra. When entire ilia were removed and processed for marrow, an average of 1.6 ± 1.0 × 10⁹ cells was obtained. Surgically resected ribs yielded lower amounts of marrow with a mean cell number of 3.2 ± 2.6 × 10⁸ per rib. Isolation of bone marrowb mononuclear cells from these preparations by density gradient centrifugation resulted in a loss of 45% of the starting cells. Human bone marrow was found to contain 5–6% T cells before gradient separation and these cells were immunologically competent as measured in vitro by responses to mitogens and alloantigens. This technique may be useful in obtaining human bone marrow for both immunologic studies and allogeneic transplantation.     

医用硫酸钙人工骨与同种异体骨修复良性骨肿瘤骨缺损的对比分析

背景：探讨医用硫酸钙人工骨可替代同种异体骨作为骨缺损的修复材料的可行性。 目的：观察医用硫酸钙人工骨材料治疗良性骨肿瘤骨缺损的临床疗效。 方法：纳入应用医用硫酸钙人工骨材料于临床修复良性骨肿瘤刮除术后骨缺损病例31例和同种异体骨材料修复病例36例。观察植入材料后4,8,12周摄X射线片植骨吸收情况及植骨材料降解率。 结果与结论：全部病例均获随访3个月以上。两组病例在随访期间植骨材料降解率差异无显著性意义。良性骨肿瘤植骨区无复发。患者植入材料后3个月X射线片示骨缺损部位有新骨生成。结果表明医用硫酸钙人工骨材料临床疗效和同种异体骨接近。     

骨形态发生蛋白与自体骨移植治疗四肢长骨骨不连的Meta分析

背景:骨形态发生蛋白具有强大的骨诱导特性,已被证实能够促进骨折、骨缺损等疾病的骨愈合。但目前国内外针对骨形态发生蛋白用于治疗骨不连的研究较少,并且各研究结果间存在争议,使得骨形态发生蛋白治疗四肢长骨骨不连的疗效尚不明确。目的:通过Meta分析,系统评价骨形态发生蛋白相比自体骨移植治疗四肢长骨骨不连的优势和不足。方法:计算机检索Pub Med、Elsevier、Web of Science、Cochrane Library、CNKI及万方等数据库建库至2019年4月发表的文献,筛选出与骨形态发生蛋白治疗四肢长骨骨不连相关的随机或非随机临床对照研究,并对纳入的文献进行质量评价和数据提取,采用Cochrane系统提供的Rev Man5.1软件对结局指标进行Meta分析。结果与结论:(1)共纳入8篇文献,其中随机对照试验和非随机对照试验各4篇,多为30-124例的小样本量研究,共计613例骨不连患者,观察组采用骨形态发生蛋白或骨形态发生蛋白联合骨移植,对照组采用自体骨移植;(2)Meta分析显示:骨形态发生蛋白或骨形态发生蛋白联合骨移植与自体骨移植的术后愈合率、感染率、二次手术率比较差异无显著性意义(P> 0.05);骨形态发生蛋白联合骨移植与自体骨移植的术后功能优良率比较差异无显著性意义(P>0.05);骨形态发生蛋白联合自体骨移植的平均愈合时间短于自体骨移植[WMD=-1.24,95%CI(-1.70,-0.79),P <0.01];骨形态发生蛋白或骨形态发生蛋白联合骨移植的手术时间短于自体骨移植(P <0.01);单独应用骨形态发生蛋白的术中出血量少于自体骨移植(P <0.05);骨形态发生蛋白联合自体骨移植的治疗费用高于自体骨移植(P <0.01);单独应用骨形态发生蛋白与自体骨移植的住院时间比较差异无显著性意义(P>0.05);(3)结果表明骨形态发生蛋白能够为自体骨移植提供一种可行的替代方法,同时也是自体骨移植物的安全佐剂,具有加速骨折愈合的潜在优势,但目前的证据暂不支持骨形态发生蛋白联合自体骨移植。     

Transdifferentiation between bone and fat on bone metabolism

The transdifferentiation of bone and fat is a new insight in studying the increasingly bone marrow fat in the process of osteoporosis of elderly or menopause crowd which is increasing in prevalence. The loss of bone mass in osteoporosis is multifactorially determined and includes genetic, hormonal and environmental determinants. Although it has long been considered whether the transdifferentiation process does exist in vivo and whether it could be find in the same individual, interaction between skeleton and adipose tissue has been proved pre-clinically and clinically by increasing evidence. Here we focus on the current understanding of the transdifferentiation between bone and fat, the molecular interactions and future clinical implications of recent studies linking the transdifferentiation to bone metabolism diseases. Furthermore, a set of recommendations of bone and fat transdifferentiation on bone metabolism are also presented to facilitate evaluation of this magic process.     

Effect of embryonic bone tissue on bone regeneration

Fragmented embryonic bone tissue stimulates bone regeneration. Bone formation starts not from implanted embryonic fragments, but in intact periosteum and endosteum containing cambial cells of the osteodifferon. In rabbits, recovery of damaged radial bone after implantation of fragmented embryonic bone tissue into bone defect was associated with a pronounced periosteal reaction and focal resorption of intact ulnar bone. Consolidation of damaged radial bone without implantation of fragmented embryonic bone tissue was incomplete in all experimental animals. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130 No. 10, pp. 469–474, October, 2000     

Theoretical study of bone sialoprotein in bone biomineralization

Bone sialoprotein (BSP) is an acidic, non-collagenous protein specific to bone proposed previously to promote hydroxyapatite (HAP) nucleation and modulate HAP nanocrystal growth. Specifically, two phosphorylated acidic amino acid sequences in BSP, highly conserved across several vertebrates, are the proposed active sites. We selected one of these sites, i.e. (Sp)(2)E(8), where Sp represents a phosphoserine as a model peptide to study the role of BSP. We used molecular dynamics simulations to determine whether an α-helix or a random coil peptide conformation promotes templated HAP nucleation. A bioinformatics method helps infer preferential crystal growth directions by predicting the likely peptide conformations adsorbed on the (001), (100), and (110) crystal faces of HAP. Results suggest that, independent of conformation, no stable nucleating template is formed and, thus, the ion distributions in the vicinity of the peptide that eventually lead to a stable nucleus start out with disordered arrangements of ions. When adsorbed on all three faces, the Sp residues bind strongly regardless of the peptide conformation, and the Glu residues show different propensities to form helical conformations. The lack of geometrical templating between the peptide residues and all HAP surface sites indicates that adsorption and subsequent crystal growth modulation may be structurally nonspecific.     

缓释型重组人骨形态发生蛋白2/壳聚糖生物骨修复材料诱导骨形成

背景：重组人骨形态发生蛋白2在体内半衰期短、易降解代谢,达不到理想的骨再生效果。 目的：制备缓释型重组人骨形态发生蛋白2/壳聚糖生物骨修复材料,并观察其缓释性能、骨诱导活性。 方法：将重组人骨形态发生蛋白2与壳聚糖混合制备壳聚糖膜,涂覆于生物骨修复材料表面,ELISA方法检测其体外释药性能。茜素红染色检测缓释型人骨形态发生蛋白2/壳聚糖生物骨材料、重组人骨形态发生蛋白2生物骨材料、单纯骨填充材料诱导C2C12细胞骨钙蛋白的形成,观察其诱导成骨细胞能力。同时将3种骨修复材料植入清洁级KM小鼠股部肌袋内,2周后检测新生骨Ca2+离子含量,评价其异位骨诱导能力。 结果与结论：材料表面的壳聚糖膜分布均匀,负载的重组人骨形态发生蛋白2呈团簇状。重组人骨形态发生蛋白2/壳聚糖生物骨修复材料体外释药存在突释,前4 d释放量达总药量的50%,持续至12 d,释药量达到90%,第18天时释放完全。与单纯骨填充材料、重组人骨形态发生蛋白2生物骨材料相比,缓释型人骨形态发生蛋白2/壳聚糖生物骨修复材料诱导C2C12细胞向成骨晚期分化能力与异位骨形成能力显著增强(P < 0.05)。结果提示缓释型人骨形态发生蛋白2/壳聚糖生物骨修复材料缓释性能好,促进骨形成能力强。     

Physiologically clotted fibrin-calcined bone composite--a possible bone graft substitute

Fibrin plays a major role in blood clotting and is important in wound healing. In the present study, physiologically clotted fibrin (PF) and calcined bone (CB) both of bovine origin were used in the preparation of a bone graft material with chitosan (C) as a binder. This bone graft (PF-CB) was characterized by stress-strain analysis, X-ray diffraction (XRD) studies, scanning electron microscopy, differential scanning calorimetry, thermogravimetric analysis, and FTIR spectroscopy. Thermal studies revealed that the incorporation of CB into PF did not alter the thermal stability of fibrin, although it affects the total loss percentage. The composition containing 24:1:15 (PF:C:CB) on dry weight basis exhibited maximum compressive strength, and the same composite was used for characterization studies. The XRD studies have shown the amorphous nature of the implant. SEM pictures revealed the heterogeneity and porous nature of the implant. PF in combination with CB is expected to exhibit osteoinductivity because fibrin, the osteoinductive protein, acts as an angiogenic factor, whereas CB provides calcium and phosphate ions that are needed for new bone formation.     

Prefabrication of vascularized bone graft using guided bone regeneration

This article describes the prefabrication of a vascularized bone graft composed of autologous particulate cancellous bone and marrow (PCBM), a vessel bundle, and a biodegradable membrane. The PCBM was placed around the saphenous vessel bundle of rats and rolled with a biodegradable membrane of L-lactide-epsilon-caprolactone copolymer to prepare the prefabricated vascularized bone graft (group A). As controls, combinations of PCBM and membrane (group B), vessel bundle and membrane (group C), and PCBM and vessel bundle (group D) were prepared. A radiographic study revealed radio-opacity in the implantation site of group A 1 week later, in contrast to the other groups. Newly formed bone in the membrane roll was histologically confirmed, and neomicrovasculature circulating from the vessel bundle through the newly formed bone tissue was observed. The increase in alkaline phosphatase activity and osteocalcin content was significant for the group A preparation compared with the other groups. We concluded that the combination of autologous PCBM, a vessel bundle, and a biodegradable membrane was promising in the prefabrication of vascularized bone with good blood circulation.