Combined use of platelet-rich plasma and autologous bone grafts in the treatment of long bone defects in mini-pigs

The use of platelet-rich plasma (PRP) for improving of bone defect healing is discussed controversially. The aim of this study was to assess the effect of PRP in combination with autologous cancellous graft on bone defect healing in a critical metaphyseal long bone defect. A critical size defect in the tibial metaphysis of 16 mini-pigs was filled either with autologous cancellous graft as control group or with autologous cancellous graft combined with autologous PRP. Compared to native blood platelets were enriched about 4.9-fold in the PRP. After 6 weeks, the specimens were assessed by X-ray and histological evaluation. Histomorphometrical analysis revealed that the area of new bone was significantly higher in the PRP group concerning the central area of the defect zone (p < 0.02) as well as the cortical defect zone (p < 0.01). All defects showed substantial new bone formation, but only defects of the PRP group regenerated entirely. The PRP group was superior to the control group even in the semi-quantitative assessment of the osseous bridging in both observed areas of the defect. Within the limits of the present study it could be demonstrated that PRP combined with autologous cancellous graft leads to a significantly better bone regeneration compared to isolated application of autologous cancellous graft in an in vivo critical size defect on load-bearing long bones of mini-pigs.     

Platelet‐rich plasma on calcium phosphate granules promotes metaphyseal bone healing in mini‐pigs

The role of platelet‐rich plasma (PRP) as a promoter of bone healing remains controversial. The aim of this study was to investigate the effect of PRP in combination with calcium phosphate granules (CPG) on bone defect healing in a metaphyseal long bone defect. A metaphyseal bone defect at the proximal tibia of 16 mini‐pigs was filled with CPG combined with autologous PRP or CPG solely (control group). The PRP showed 4.4‐fold more platelets compared to peripheral blood. Six weeks after surgery the radiological and histomorphometrical evaluations showed significantly more bone formation in the PRP group in the central area of the defect zone (p < 0.01) as well as the cortical defect zone (p < 0.04). Furthermore, the resorption rate of CPG was increased in animals who received PRP. Nevertheless there were only isolated instances of complete osseous bridging of the bone defects even in the PRP group. This study demonstrates that a PRP‐CPG composit promotes bone regeneration but does not lead to a solid fusion of a tibial defect in mini‐pigs. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1448–1455, 2010     

Differences of bone healing in metaphyseal defect fractures between osteoporotic and physiological bone in rats

Discrepancies in bone healing between osteoporotic and non-osteoporotic bone remain uncertain. The focus of the current work is to evaluate potential healing discrepancies in a metaphyseal defect model in rat femora. Female Sprague-Dawley rats were either ovariectomized (OVX, n = 14) and combined with a calcium-, phosphorus- and vitamin D3-, soy- and phytoestrogen-free diet or received SHAM operation with standard diet rat (SHAM, n = 14). Three months post-ovariectomy, DEXA measurement showed a reduction of bone mineral density reflecting an osteoporotic bone status in OVX rats. Rats then underwent a 3 mm wedge-shaped osteotomy at the distal metaphyseal area of the left femur stabilized with a T-shaped mini-plate and allowed to heal for 6 weeks. Biomechanical competence by means of a non-destructive three-point bending test showed significant lower flexural rigidity in the OVX rats at 3 mm lever span compared to SHAM animals (p = 0.048) but no differences at 10 mm lever span. Microcomputer tomography (μCT) showed bridging cortices and consolidation of the defect in both groups, however, no measurable differences were found in either total ossified tissue or vascular volume fraction. Furthermore, histology showed healing discrepancies that were characterized by cartilaginous remnant and more unmineralized tissue presence in the OVX rats compared to more mature consolidation appearance in the SHAM group. In summary, bone defect healing in metaphyseal bone slightly differs between osteoporotic and non-osteoporotic bone in the current 3 mm defect model in both 3 mm lever span biomechanical testing and histology.     

Two‐step stem cell therapy improves bone regeneration compared to concentrated bone marrow therapy

Adult stem cells are a promising tool to positively influence bone regeneration. Concentrated bone marrow therapy entails isolating osteoprogenitor cells during surgery with, however, only low cells yield. Two step stem cell therapy requires an additional harvesting procedure but generates high numbers of progenitor cells that facilitate osteogenic pre‐differentiation. To further improve bone regeneration, stem cell therapy can be combined with growth factors from platelet rich plasma (PRP) or its lysate (PL) to potentially fostering vascularization. The aim of this study was to investigate the effects of bone marrow concentrate (BMC), osteogenic pre‐differentiation of mesenchymal stromal cells (MSCs), and PL on bone regeneration and vascularization. Bone marrow from four different healthy human donors was used for either generation of BMC or for isolation of MSCs. Seventy‐two mice were randomized to six groups (Control, PL, BMC, BMC + PL, pre‐differentiated MSCs, pre‐differentiated MSCs + PL). The influence of PL, BMC, and pre‐differentiated MSCs was investigated systematically in a 2 mm femoral bone defect model. After a 6‐week follow‐up, the pre‐differentiated MSCs + PL group showed the highest bone volume, highest grade of histological defect healing and highest number of bridged defects with measurable biomechanical stiffness. Using expanded and osteogenically pre‐differentiated MSCs for treatment of a critical‐size bone defect was favorable with regards to bone regeneration compared to treatment with cells from BMC. The addition of PL alone had no significant influence; therefore the role of PL for bone regeneration remains unclear. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1318–1328, 2019.     

重组人工骨修复实验性骨缺损影像学评价

[目的]探讨重组人胰岛素样生长因子-1（recombinant human insulinlike growth factor-1，rhIGF-1）／珊瑚羟基磷灰石（coralline hydroxyapatite，CHA）／自体红骨髓（autogeneous red bone marrow，ARBM）复合修复骨缺损的能力。[方法]成年中国家兔54只，随机分为3组，制成双侧桡骨中段11mm骨-骨膜全层缺损模型，每组18只，每组动物左右两侧缺损分别随机植入2种不同材料：1组两侧分别植入材料A（CHA／ARBM／rhlGF．1）和B（CHA／ARBM）；2组植入C（CHA／rhIGF-1）和D（CHA）；3组植入E（自体皮质骨）和F（缺损旷置）。术后行大体、X线（2、4、8、12周）和^99mTc—MDP骨扫描（12周）观察。[结果]A组X线片显示桥接骨痂生长良好，12周时缺损修复。12周^99mTc—MDP骨显像示A和E组修复区高度核浓聚。[结论]CHA／ARBM／rhIGF-1重组人工骨移植可协同实现骨传导、骨诱导和骨再生作用，促进骨缺损重建。     

Periosteal progenitor cell fate in segmental cortical bone graft transplantations: implications for functional tissue engineering.

A murine segmental femoral bone graft model was used to show the essential role of donor periosteal progenitor cells in bone graft healing. Transplantation of live bone graft harvested from Rosa 26A mice showed that approximately 70% of osteogenesis on the graft was attributed to the expansion and differentiation of donor periosteal progenitor cells. Furthermore, engraftment of BMP-2-producing bone marrow stromal cells on nonvital allografts showed marked increases in cortical graft incorporation and neovascularization, suggesting that gene-enhanced, tissue engineered functional periosteum may improve allograft incorporation and repair. INTRODUCTION: The loss of cellular activity in a structural bone allograft markedly reduces its healing potential compared with a live autograft. To further understand the cellular mechanisms for structural bone graft healing and repair and to devise a therapeutic strategy aimed at enhancing the performance of allograft, we established a segmental femoral structural bone graft model in mice that permits qualitative and quantitative analyses of graft healing and neovascularization. MATERIALS AND METHODS: Using this segmental femoral bone graft model, we transplanted live isografts harvested from Rosa 26A mice that constitutively express beta-galactosidase into their wildtype control mice. In an attempt to emulate the osteogenic and angiogenic properties of periosteum, we applied a cell-based, adenovirus-mediated gene therapy approach to engraft BMP-2-producing bone marrow stromal cells onto devitalized allografts. RESULTS: X-gal staining for donor cells allowed monitoring the progression of periosteal progenitor cell fate and showed that 70% of osteogenesis was attributed to cellular proliferation and differentiation of donor progenitor cells on the surface of the live bone graft. Quantitative muCT analyses showed a 3-fold increase in new bone callus formation and a 6.8-fold increase in neovascularization for BMP-2/stromal cell-treated allograft compared with control acellular allografts. Histologic analyses showed the key features of autograft healing in the BMP-2/stromal cell-treated allografts, including the formation of a mineralized bone callus completely bridging the segmental defects, abundant neovascularization, and extensive resorption of bone graft. CONCLUSIONS: The marked improvement of healing in these cellularized allografts suggests a clinical strategy for engineering a functional periosteum to improve the osteogenic and angiogenic properties of processed allografts.     

Healing of segmental bone defects with granular porous hydroxyapatite augmented with recombinant human osteogenic protein-1 or autologous bone marrow.

Hydroxyapatite is a synthetic bone graft, which is used for the treatment of bone defects and nonunions. However, it is a rather inert material with no or little intrinsic osteoinductive activity. Recombinant human osteogenic protein-1 (rhOP-1) is a very potent biological agent, that enhances osteogenesis during bone repair. Bone marrow contains mesenchymal stem cells, which are capable of new bone formation. Biosynthetic bone grafts were created by the addition of rhOP-1 or bone marrow to granular porous hydroxyapatite. The performance of these grafts was tested in a sheep model and compared to the results of autograft, which is clinically the standard treatment of bone defects and nonunions. A 3 cm segmental bone defect was made in the tibia and fixed with an interlocking intramedullary nail. There were five treatment groups: no implant (n=6), autograft (n=8), hydroxyapatite alone (n=8), hydroxyapatite loaded with rhOP-1 (n=8), and hydroxyapatite loaded with autologous bone marrow (n=8). At 12 weeks, healing of the defect was evaluated with radiographs, a torsional test to failure, and histological examination of longitudinal sections through the defect. Torsional strength and stiffness of the healing tibiae were about two to three times higher for autograft and hydroxyapatite plus rhOP-1 or bone marrow compared to hydroxyapatite alone and empty defects. The mean values of both combination groups were comparable to those of autograft. There were more unions in defects with hydroxyapatite plus rhOP-1 than in defects with hydroxyapatite alone. Although the differences were not significant, histological examination revealed that there was more often bony bridging of the defect in both combination groups and the autograft group than in the group with hydroxyapatite alone. Healing of bone defects, treated with porous hydroxyapatite, can be enhanced by the addition of rhOP-1 or autologous bone marrow. The results of these composite biosynthetic grafts are equivalent to those of autograft.     

Osteogenic progenitors in bone marrow aspirates have clinical potential for tibial non-unions healing in diabetic patients

Purpose

There is a significantly higher incidence of delayed unions, non-unions, and increased healing time in diabetic patients compared with non-diabetic patients. Studies suggest that diabetics suffer from deficiencies of pancreatic stem/progenitor cells, and a clinically relevant question arises concerning the availability and functionality of progenitor cells obtained from bone marrow of diabetics for applications in bone repair.

Methods

We have evaluated the cellularity and frequency of osteogenic mesenchymal stem cells (MSCs) in bone marrow from 54 diabetic patients (12 with type 1 and 42 with type 2) with tibial non-unions. These patients were treated with bone marrow MSCs (BM-MSCs) delivered in an autologous bone marrow concentrate (BMC). Clinical outcomes and marrow cellularity were compared to 54 non-diabetic, matched patients with tibial non-unions also treated with BMC.

Results

After adjusting for age and sex, no differences were identified with respect to bone marrow cellularity and MSC number among the diabetic and non-diabetic groups and both groups received approximately the same number of MSCs on average. BMC treatment promoted non-union healing in 41 diabetic patients (76 %) and 49 non-diabetic patients (91 %), but the non-diabetic patients healed more quickly and produced a larger volume of callus.

Conclusion

We recommend that diabetic patients be treated with an increased number of progenitor cells by increasing the bone marrow aspiration volume. We also anticipate a need to extend the time of casting and non-weight bearing for diabetic patients as compared with non-diabetic patients.

     

人工骨联合自体骨髓移植技术的骨缺损修复研究与应用

目的分析人工骨联合自体骨髓移植技术治疗骨缺损的临床疗效。方法选取2011年4月至2013年9月,来本院诊治的四肢粉碎性骨折术后骨缺损患者40例,随机分为两组（A、B组）,分别行自体髂骨植骨和人工骨联合自体骨髓移植治疗四肢粉碎性骨折所致骨缺损。术后观察两组骨折愈合时间,骨折愈合率,并发症的发生及骨缺损的修复和功能重建优良率。结果两组均行6～12个月随访,平均（9.14±1.36）月,所有患者植骨术后均无切口感染、发热等并发症。A组15例骨缺损区愈合良好,住院时间平均（19.36±2.54）天,骨折愈合时间平均（5.67±1.52）个月,骨缺损的修复和功能重建评价标准,优12例,良3例,可3例,差2例,优良率75%;B组18例骨缺损区愈合良好,住院时间平均（12.19±1.52）天,骨折愈合时间平均（3.61±1.13）个月,骨缺损的修复和功能重建评价标准,优16例,良2例,可2例,差0例,优良率90%。B组骨缺损治疗效果显著优于A组。结论人工骨联合自体骨髓移植较单纯自体髂骨移植治疗骨缺损更能促进骨痂生长,加速骨折后骨缺损愈合,更加有效地减少住院时间及骨折愈合时间,骨折愈合率更高,骨缺损修复和功能重建效果更加显著。     

自体与同种异体骨移植修复四肢长骨骨缺损的对比研究

目的比较自体与同种异体骨移植修复四肢长骨骨缺损的临床效果。方法回顾性分析132例异体骨和97例自体骨修复重建四肢长骨骨缺损患者的临床治疗资料,比较两种方法愈合时间、骨性愈合评分（按Jorgenson标准）、并发症发生率及植骨失败率。结果异体骨重建组132例,4例因感染致植骨失败需行病灶清除灌洗加自体骨移植,10例发生局部排斥反应,其余118例患者术后骨缺损获得良好修复,愈合时间（17．6±1．9）周。骨性愈合评分2．7±0．5。自体骨重建组97例,9例出现供区疼痛、切口感染及局部皮肤麻木等供区并发症,骨缺损均获得良好修复,愈合时间（17．4±23）周,骨性愈合评分2．84±0.3。两组之间在愈合时间、并发症发生率以及愈合评分方面的差异无统计学意义（P〉0．05）;在植骨失败率方面的差异有统计学意义（P〈0．05）。结论运用同种异体骨和自体骨移植重建四肢长骨骨缺损,均能获得满意结果且疗效相似。异体骨移植术后感染致植骨失败以及排斥反应发生率较高,而自体骨移植则多表现为供区的并发症。     

Mineral loss in cortical and trabecular bone during high-dose prednisone treatment

Summary To evaluate the effect of prednisone and triple treatment (sodium fluoride, calcium, and vitamin D) on trabecular and cortical bone serial bone mineral content (BMC) measurements were made at a metaphyseal (BMC_D) and diaphyseal (BMC_P) site on the forearm on 31 consecutive and previously bone-healthy patients scheduled for at least 24 weeks high-dose prednisone treatment. The patients were randomized into two further treatment groups: group I (n=16) received prednisone plus triple treatment and group II (n=15) received only prednisone. The two groups were similar with regard to age, sex, prednisone dose, and initial BMC. During 24 weeks treatment, BMC_D (partially representing trabecular bone) and BMC_P (mainly representing cortical bone) fell significantly and similarly, demonstrating that there is no preventive effect on bone mineral loss on the triple regimen. The BMC fall after 12 weeks was significantly more pronounced for metaphyseal (partially trabecular) than for diaphyseal (cortical) bone, whereas the values did not differ significantly after 24 weeks; this indicates a greater sensitivity to the hormone treatment of trabecular bone. In the entire group, the fall in BMC correlated positively with individual prednisone dose, significant at the diaphyseal site (r=0.39,P<0.05), but not at the metaphyseal site (r=0.31, P=0.08). It is concluded that corticosteroid-induced osteopenia is a diffuse bone disease which affects trabecular as well as cortical bone, suggesting that BMC measured on the forearm reflects changes in bone mineral at other locations.     

The role of cell type in bone healing mediated by ex vivo gene therapy

Background The ideal cellular vehicle for use in cell-mediated gene therapy to enhance bone healing has not yet been identified. The purpose of this study was to compare the capacity of two types of cells transduced with retro-bone morphogenetic protein 4 (BMP4)—muscle-derived cells (MDCs) and unfractioned bone marrow stromal cells (BMSCs).Method Primary rat MDCs and unfractioned rat BMSCs were transduced with a retrovirus to express BMP4. A 7-mm, critical-sized femur defect was created in adult rats, and 5×10⁶ transduced cells were implanted into the femoral defect. Bone healing was monitored radiographically and histologically at 4, 8, and 12 weeks post-implantation.Results All specimens in the MDC-BMP4 group and BMSC-BMP4 group showed a bridging callus at 8 and 12 weeks. At 12 weeks post-implantation the calluses of the MDC-BMP4 femora displayed significantly higher bone photodensity than the BMSC-BMP4 femora (P<0.05). Histomorphometry revealed no difference between the two treatment groups. However, non-union between newly formed and original bone was observed in none of the MDC femora but in six femora from the BMSC-BMP4 group.Conclusion Both MDCs and unfractioned BMSCs can improve healing of a critical-sized bone defect following transduction of the cells with retroBMP4. However, MDCs appear to yield superior results when compared with BMSCs in terms of improved healing of segmental defects.     

骨髓基质细胞移植修复半月板无血运区损伤的实验研究

目的比较自体与同种异体骨髓基质细胞移植对半月板无血运区损伤修复的影响。方法 40只成年新西兰大白兔随机平均分为 A、 B两组。 A组兔的骨髓基质细胞 (MSC)经体外培养后与纤维蛋白凝胶 (FG)混合,自体移植于其一侧的膝关节半月板缺损区,即 FG＋自体 MSC（自体移植组）;另一侧单纯植入 FG(FG植入组 )。于 B组兔的一侧膝关节半月板缺损区移植 FG＋同种异体 MSC(异体移植组 ),另一侧缺损不予修复 (空白对照组 )。分别于术后第 1、 2、 3个月取材,观察半月板损伤部位的组织形态学变化。结果 (1)自体移植组 :术后 1个月缺损区可见纤维组织,内有大量成纤维细胞;术后 2个月见大量软骨细胞并有胶原纤维形成;术后 3个月损伤区呈纤维软骨愈合。 (2)空白对照组 :术后 1～ 3个月缺损区始终未愈合。 (3)单纯 FG植入组 :术后 1～ 3个月缺损区可见纤维组织,内有少量成纤维细胞,没有软骨细胞生长,呈瘢痕样愈合。 (4)同种异体移植组 :与自体移植组所见大致相同,但有 3侧缺损区可见大量淋巴细胞浸润,胶原纤维少。结论骨髓基质细胞移植可促进半月板无血运区损伤的愈合,同种异体骨髓基质细胞移植修复半月板无血运区损伤发生免疫排斥反应的机率较低。     

Repair of large segmental bone defects using bone marrow stromal cells with demineralized bone matrix

Objective: The aim of the present study was to evaluate the effect of tissue‐engineered constructs on repair of large segmental bone defects in goats. Methods: Allogenic demineralized bone matrix (aDBM) was seeded with autologous marrow stromal cells (aMSC) for seven days to construct DBM–MSC grafts prior to implantation. 24 goats were randomly divided into three groups (eight in each). In each group, 3 cm diaphyseal femoral defects were created unilaterally, and subsequently filled with the DBM‐MSC grafts, DBM alone and an untreated control, respectively. Radiological analysis and biomechanical evaluation were performed at 12 and 24 weeks after operation. Results: Obvious increases in radiological scoring and biomechanical strength were found in the DBM‐MSC group when compared to the DBM group. X‐ray examination showed excellent bone healing in the DBM‐MSC group, whereas only partial bone repair was seen in the DBM group, and no healing in untreated controls. Histologically, a tendency to bone regeneration and remodeling was far more obvious for the DBM‐MSC group than the DBM only and untreated controls. Conclusion: Our results strongly suggest that transplantation of bone MSC within a DBM could have advantages for the bone repair of large segmental defects.     

Restoration of bone defect and enhancement of bone ingrowth using partially demineralized bone matrix and marrow stromal cells

PURPOSE: This study aimed to investigate the capability of combining marrow stromal cells (MSC) and partially demineralized bone matrix (PDBM) to fill bone defect and enhance bone ingrowth using a canine non-weight-bearing gap model. METHODS: Custom-made implants with 3mm gap between the porous surface and the host bone were used. The implants were inserted into the distal femurs of 25 mongrel dogs and the gaps were randomly assigned to be filled with culture-expanded autologous MSC-loaded PDBM, autograft, fresh-frozen allograft, PDBM alone, or nothing as controls. Histomorphometry using backscattered scanning electron microscopic examination, and mechanical push-out test were performed at 6 months after surgery. RESULTS: Histomorphometry showed that amounts of bone regeneration in the gap and bone ingrowth into the porous-coated surface in the MSC-loaded PDBM-treated group were comparable to those of autograft-treated group and were significantly greater than those of allograft-treated, PDBM-treated, or non-grafted groups. Mechanical test showed the same differences. CONCLUSION: The results of this study showed that combining PDBM and autologous culture-expanded MSC restored bone stock and enhanced bone ingrowth into the porous-coated area in a canine non-weight-bearing gap model. This combination may provide an option for reconstructing bone defect when we perform a cementless revision arthroplasty.     

Influence of short-term adenoviral vector and prolonged lentiviral vector mediated bone morphogenetic protein-2 expression on the quality of bone repair in a rat femoral defect model

The objective of this study was to compare the efficacy of adenoviral and lentiviral regional gene therapy in a rat critical sized femoral defect model. The healing rates and quality of bone repair of femoral defects treated with syngeneic rat bone marrow cells (RBMCs) transduced with either lentiviral vector (Group I) or adenoviral vector (Group II) expressing bone morphogenetic protein-2 (BMP-2) gene were assessed. RBMCs transduced with the adenoviral vectors produced more than 3 times greater (p < 0.001) BMP-2 when compared to RBMCs transduced with lentiviral vectors in an in vitro evaluation. Serial bioluminescent imaging demonstrated short duration luciferase expression (less than 3 weeks) in defects treated with RBMCs co-transduced with two adenoviral vectors (Group IV; adenovirus expressing BMP-2 and luciferase [Ad-BMP-2 + Ad-Luc]). In contrast, the luciferase signal was present for 8 weeks in defects treated with RBMCs co-transduced with two lentiviral vectors (Group III; lentivirus expressing BMP-2 and luciferase gene [LV-BMP-2 + LV-Luc]). There were no significant differences with respect to the radiological healing rates (p = 0.12) in defects treated with lentiviral versus adenoviral mediated BMP-2 gene transfer. Biomechanical testing of healed Group I femoral specimens demonstrated significantly higher energy to failure (p < 0.05) when compared to Group II defects. Micro CT analysis revealed higher bone volume/tissue volume fraction (p = 0.04) in Group I defects when compared to Group II defects. In conclusion, prolonged BMP-2 expression associated with lentiviral mediated gene transfer demonstrated a trend towards superior quality of bone repair when compared to adenoviral mediated transfer of BMP-2. These results suggest that the bone repair associated with regional gene therapy is influenced not just by the amount of protein expression but also by duration of protein production. This observation needs validation in a more biologically challenging environment where differences in healing rates and quality of bone repair are more likely to be significantly different.     

假体周围骨溶解性骨缺损的转骨形态发生蛋白-2基因治疗

目的 模拟假体周围骨溶解环境,观察骨形态发生蛋白-2(BMP-2)基因治疗假体周围骨溶解性骨缺损的效果.方法 成年雄性Beagle犬6条,于股骨外髁造成假体周围3mm骨缺损区.1条动物的左侧缺损区植入1ml平均直径1μm的钛合金颗粒混悬液,右侧植入1ml磷酸盐缓冲液(PBS),观察造模结果;其他5条动物双侧植入1ml钛合金颗粒混悬液,于术后2个月取出假体,植入转BMP-2基因冻干骨或单纯冻干骨,二次术后3个月取材,行组织学、组织形态计量学观察植骨愈合替代及界面骨整合情况.结果 颗粒造模术后2个月可见典型的骨溶解界膜组织形成.翻修术后3个月,冻干骨组见较多植骨残余,假体-骨界面基本为软组织界膜,假体骨接触率(BIC)为(1.38±1.22)%;基因治疗组见少量植骨残余,假体-骨界面有点状骨接触,BIC为(12.96±1.61)%,两组差异有统计学意义(P<0.01).结论 采用BMP-2基因治疗可提高假体周围骨溶解性骨缺损的界面骨整合.     

The influence of hydroxyapatite granules on the healing of a segmental defect filled with autologous bone marrow.

Hydroxyapatite(HA) ceramics are frequently used as a bone graft substitutes for the filling of bony defects. The addition of autologous bone marrow to HA ceramics does improve defect healing. There is conflicting evidence in the literature whether autologous bone marrow transplantation alone is as effective as the combination of HA ceramics and bone marrow combined. It was the purpose of this study to identify the role of additional HA ceramic granules on the healing of a sheep tibia segmental defect filled with autologous bone marrow. After permission of the local animal rights committee was obtained, a 3 cm segmental defect in the midshaft of 31 adult sheep was stabilized with an unreamed tibia nail. The animals were divided into 4 groups according to the mode of defect filling: HA plus autologous bone marrow (HA + MAR) (n = 8), autologous bone marrow (MAR) (n = 9), empty defect (DEF) (n = 6), cancellous bone graft (CAN) (n = 8). After three months follow up animals were sacrificed and analysed for the key parameters of union and maximum torque at failure. One nonunion was present in each of the HA + MAR, MAR, and CAN groups. Four of the six animals in the DEF group developed a nonunion. Maximum torque at failure was reported as percentage of the intact contralateral tibia: HA + MAR 39% +/- 24%, MAR 26% +/- 17%, DEF 22% +/- 13%, CAN 41% +/- 20%. The difference between the groups was statistically significant, but appeared to be relevant. We conclude from our data, that HA ceramics do improve healing of a segmental defect in the sheep tibia filled with autologous bone marrow. The results of this combination are comparable to cancellous autograft.     

Xenogenic demineralized bone matrix and fresh autogenous cortical bone effects on experimental bone healing: radiological, histopathological and biomechanical evaluation

Background  Bone grafting is used to enhance healing in osteotomies, arthrodesis, and multifragmentary fractures and to replace bony loss resulting from neoplasia or cysts. They are source of osteoprogenitor cells and induce bone formation and provide mechanical support for vascular and bone ingrowth. Autografts are used commonly but quantity of harvested bone is limited. The aim of this study is to evaluate autograft and new xenogenic bovine demineralized bone matrix (DBM) effects on bone healing process. Materials and methods  Twenty male White New Zealand rabbits were used in this study. In group I (n = 10) the defect was filled by xenogenic DBM and in autograft group the defect was filled by fresh autogenous cortical graft and fixed by cercelage wire. Radiological, histopathological and biomechanical evaluations were performed blindly and results scored and analyzed statistically. Results  Statistical tests did not reveal any significant differences between two groups on the 14th postoperative day radiographically (P > 0.05). There was a significant difference for union on 28th and 42nd postoperative days and for remodeling at on the 56th postoperative day radiologically (P < 0.05). Statistical tests did not support any significant differences between two groups for radiological bone formation (P > 0.05). Histopathological and biomechanical evaluation revealed no significant differences between two groups. Conclusions  The results of this study indicate that satisfactory healing occurred in rabbit radius defect filled with xenogenic bovine DBM. Complications were not identified and healing was faster, same as in cortical autogenous grafting.     

The use of BoneSource hydroxyapatite cement for traumatic metaphyseal bone void filling

OBJECTIVE: This prospective, randomized study was performed to determine whether a new, in situ setting hydroxyapatite cement is as safe or effective as autologous cancellous bone graft for the treatment of metaphyseal bone voids secondary to trauma. This was a multicenter study including Level I trauma centers and university hospitals. Thirty-eight patients who sustained an acute closed or open type I fracture of the humerus, radius, ulna, femur, tibia, or calcaneus and had a traumatic bone void requiring grafting of the metaphyseal or cancellous bone area were enrolled. Open reduction and internal fixation of the fracture was performed with use of either autologous cancellous bone or BoneSource hydroxyapatite cement to fill traumatic metaphyseal voids. Main outcome measures included maintenance of reduction, fracture healing, pain at defect site, pain at donor site, and clinical function of the limb. RESULTS: Patients treated with BoneSource had an 83% success rate in maintaining reduction, whereas patients treated with autograft had a 67% success rate. A successful clinical outcome, as measured by a healed fracture with minimal to no pain, moderate to maximum function, and no or minor donor site complications, was seen in 69% of patients treated with BoneSource and 57% of patients treated with autograft. In patients with at least 1 year of follow-up, the overall success rate was 79% in the BoneSource group and 70% in the autograft group. CONCLUSION: BoneSource is safe and effective when used to fill traumatic metaphyseal bone voids. It is at least as good as autograft for treatment of these defects.