The effect of demineralized bone matrix-calcium sulfate with vancomycin on calcaneal fracture healing and infection rates: a prospective study

BACKGROUND: Displaced intra-articular calcaneal fractures may have a central cancellous bone defect area. We hypothesized that human demineralized bone matrix (DBM) calcium sulfate (CaSO(4)) might act as a reasonable alternative to autograft in calcaneal fractures. When combined with antibiotic powder, this bone graft substitute also may act as a local antibiotic delivery device. This is the first clinical study evaluating bone healing and complications associated with DBM-calcium sulfate bone graft substitute in the treatment of displaced intra-articular calcaneal fractures with a central cancellous bone defect. METHODS: Over a 29-month period, 33 displaced intra-articular calcaneal fractures with central cancellous defects were treated with open reduction and internal fixation (ORIF) and grafting with vancomycin/DBM-calcium sulfate bone graft substitute. Eleven fractures without bone defects were treated with ORIF only. Patient demographics, medical history, and CT fracture classification were recorded. Postoperatively, fractures were monitored every 2 weeks for healing and complications. RESULTS: The mean time to union was 8.2 weeks in the grafted, while the control group mean time to union was 10.4 weeks (p = 0.0117). Wound problems occurred in five (15%) of the 33 patients with grafting, all in type III fractures with severe soft-tissue swelling, and included two minor wound healing delays, and three serious wound problems. At a mean followup time of 22.4 months, no DBM-calcium sulfate grafted calcaneus demonstrated evidence of osteomyelitis. CONCLUSIONS: This is the first study examining human DBM-calcium sulfate bone graft substitute to treat displaced intra-articular calcaneal fractures. Based on these initial data, human DBM-calcium sulfate acted as an acceptable and safe autograft alternative in displaced intra-articular calcaneal fractures with moderate (5 cc to 10 cc) central cancellous bone defects.     

Treatment of pseudoarthrosis of the scaphoid bone by bone transplantation (modified Matti-Russe operation)]

Author reviews possibilities in the treatment of nonunited scaphoid fractures. Different techniques with cancellous bone grafting are described and his own function-stable grafting osteosynthesis presented. Indications for his operation are well delineated and with regards to good results their accurate application is emphasized. 352 cases were treated using his grafting method in 94 per cent good results was obtained passing by 14 per cent the average results of 80 per cent with other grafting techniques.     

Decalcified and undecalcified cancellous bone block implants do not heal diaphyseal defects in dogs

Summary In a previous study it has been shown that granulae of decalcified bone matrix do not induce bony healing of 8-week-old mid-diaphyseal defects in dogs. The aim of this study was to test whether osteoinduction combined with the osteoconductive mechanisms provided by the natural structure of cancellous bone blocks would yield better results. A 30-mm-long diaphyseal defect of the left ulna was created in eight adult mongrel dogs and the bone was stabilized with a plate. A Silastic spacer was inserted in the defect for 8 weeks, followed by implantation of frozen undecalcified or decalcified allogeneic cancellous bone blocks for 16 weeks. Healing was analyzed using morphologic methods. At 16 weeks after implantation all grafts had been resorbed. In the decalcified group one defect healed, while none in the other group did so. The implant material was bioassayed in nude rats for osteoinductivity, which was found to be low in decalcified matrix and not detectable in undecalcified bone. Conclusion: Allogeneic cancellous bone blocks, demineralized or not, have no osteoinductive capacity and no osteoconductive function that promotes healing of mid-diaphyseal bone defects in dogs.     

Osseous healing with a composite of allograft and demineralized bone matrix: adverse effects of smoking

We report on our use of a composite graft of lyophilized cancellous allogenic chips and demineralized bone matrix (DBM; Grafton; Osteotech, Eatontown, NJ) to manage traumatic osseous defects and nonunions. Data were prospectively collected from all patients who received this composite bone graft between 1996 and 2000. Only acute fractures with bone loss resulting in a uncontained defect and atrophic non-unions were included in the present study. Demographic data and complications related to composite use, tobacco use, and other comorbidities that could affect healing were evaluated. One hundred seven patients (112 bone graft sites) were followed up for a mean of 32 months (range, 12-60 months). Graft sites included the forearm, femur and tibia. Of the 112 patients, there were 56 smokers (25 non-unions and 31 fractures) and 56 non-smokers (28 fractures and 28 non-unions). Healing occured in 38/56 smokers compared with 49/56 non-smokers. In failed cases, smoking was characteristic in 7/9 non-unions and 11/16 fractures. There were 26 acute uncontained injuries, 29 acute contained defects, and 67 nonunions. Grafting sites were radius/ulna (13 cases), humerus (17), femur (31), and tibia/fibula (51). Significant comorbidities were diabetes mellitus (4 cases), fungal osteomyelitis (1), and pulmonary alveolar proteinosis (1). Eight (73%) of the 11 patients with graft failure had a significant smoking history. This composite graft is an option for managing osseous defects and nonunions traditionally treated with autologous bone grafting but should be used with caution when treating patients who are smokers.     

Cancellous bone donor site regeneration

Patients requiring cancellous bone grafting of an extensive deficit or multiple grafting procedures often lack a sufficient quantity of autogenous cancellous donor bone. This study was designed to determine the potential for reharvesting autogenous cancellous bone donor sites in a canine model. Fixed-sized cancellous bone grafts were harvested from the ilium of 12 mature, conditioned dogs. Ilia containing the donor sites were removed from groups of 3 dogs at intervals of 6 weeks, 3 months, 6 months, and 1 year. The donor sites were evaluated by roentgenograms, histology, and histomorphometric analysis and were compared to the opposite, nonoperated ilia, which served as controls. The analysis revealed a gradual replacement of the surgical defect with new cancellous bone by 1 year. Donor site reharvesting is a potential alternative to multiple site grafting or the use of allograft material.     

骨段撑开转移治疗骨缺损国外进展

节段性骨缺损是下肢开放性骨折中较严重的损伤,传统的治疗包括:采用外固定支架稳定骨折、应用游离组织移植修复软组织缺损创面以及用带血管或不带血管的骨移植修复骨缺损.骨段撑开转移是治疗骨缺损的一种新方法.适宜治疗3～12 cm的骨干缺损,仅需行少量松质骨移植以促进局部骨愈合.而常规治疗方法植骨量较大.因而,供骨区并发症较少.而且,不需行游离组织移植修复创面.缺点是相对复杂,治疗时间长.当病例选择适当以及对技术掌握完善时,对某些骨缺损病例的治疗,才能充分发挥其优越性.     

Accelerated repair of cortical bone defects using a synthetic extracellular matrix to deliver human demineralized bone matrix.

Injectable hydrogel and porous sponge formulations of Carbylan-GSX, a crosslinked synthetic extracellular matrix (ECM), were used to deliver human demineralized bone matrix (DBM) in a rat femoral defect model. A cortical, full-thickness 5-mm defect was created in two femurs of each rat. Six rats were assigned to each of five experimental groups (thus, 12 defects per group). The defects were either untreated or filled with Carbylan-GSX hydrogel or sponges with or without 20% (w/v) DBM. Radiographs were obtained on day 1 and at weeks 2, 4, 6, and 8 postsurgery of each femur. Animals were sacrificed at week 8 postsurgery and each femur was fixed, embedded, sectioned, and processed for Masson's Trichrome staining. The bone defects were measured from radiographs and the fraction of bone healing was calculated. The average fractions of bone healing for each group were statistically different among all groups, and all treatment groups were significantly better than the control group. The Carbylan-GSX sponge with DBM was superior to the sponge without DBM and to the hydrogel with DBM. Histology showed that defects treated with the Carbylan-GSX sponge plus DBM were completely filled with newly generated bone tissue with a thickness comparable to native bone. Carbylan-GSX sponge was an optimal delivery vehicle for human DBM to accelerate bone healing.     

Bone marrow and recombinant human bone morphogenetic protein-2 in osseous repair

Bone marrow stem cells and recombinant human bone morphogenetic protein-2 each has the capacity to repair osseous defects. Recombinant human bone morphogenetic proteins require the presence of progenitor cells to function. It is hypothesized that a composite graft of recombinant human bone morphogenetic protein-2 and marrow would be synergistic and could result in superior grafting to autogenous bone graft. Syngeneic Lewis rats with a 5-mm critical sized femoral defect were grafted with recombinant human bone morphogenetic protein-2 and marrow, recombinant human bone morphogenetic protein-2, marrow, syngeneic cancellous bone graft, or carrier alone (control). Serial radiographs (3, 6, 9, 12 weeks) and torque testing (12 weeks) were performed. Bone formation and union were determined. The recombinant human bone morphogenetic protein-2 and marrow composite grafts achieved 100% union at 6 weeks. Recombinant human bone morphogenetic protein alone achieved 80% union by week 12. Both groups yielded a higher union rate and superior mechanical properties than did either syngeneic bone graft (38%) or marrow (47%) alone. The superior performance of recombinant human bone morphogenetic protein-2 combined with bone marrow in comparison with each component alone strongly supports a biologic synergism. This experimentation shows the clinical importance of establishing operative site proximity for the osteoinductive factors and responding progenitor cells.     

Bone grafting of cryosurgically treated bone defects: experiments in goats

It is hypothesized that cryosurgically treated bone defects are inappropriate host sites for cancellous bone grafting. The influence of autologous cancellous bone grafting on the healing of cryosurgically treated gap defects of long bones was investigated. A unilateral in vivo experiment was done to study bone strength and graft incorporation in the goat. The lining of a cylindrical defect of the femoral diaphysis was treated with a closed liquid nitrogen cryoprobe in 62 goats. Thirty-one animals received an impacted, morselized, cancellous bone graft harvested from the sternum. The other 31 animals served as controls. At 0, 4, 7, 10, 13, 16, and 26 weeks animals were euthanized and the femurs were evaluated for torsional strength, computed tomography, and histologic assessment. Specimens with a bone graft showed no significant increase in torsional strength with time compared to the controls. In all goats euthanized at 10 weeks or later, the graft was resorbed. The amount of bone apposition at the site of the cryosurgical lesion and the time at which the defect was bridged were similar in both groups. Autologous cancellous bone grafting does not accelerate healing of cryosurgically treated, stable, diaphyseal defects in the goat.     

一期开放松质骨植骨治疗感染性骨缺损的实验研究

目的 明确感染性骨折不愈合清创术后一期开放松质骨植骨的可行性，了解在感染的环境条件下，开放松质骨植骨愈合的组织病理变化过程。方法 新西兰白兔62只，制备双侧桡骨中段骨折，骨折端注射金黄色葡萄球菌制作感染性骨折模型，4周后经过x线片、病理、细菌培养来确定是否为感染。将确认为感染性骨折的47只兔，一侧桡骨行清创术并制造长度为1cm骨折端骨缺损，一期行自体松质骨植骨，伤口开放不闭合。另一侧桡骨不植骨为对照组。于第3、7天，第2、4、6、8、10、12周摄X线片，取材行EDTA脱钙，常规HE染色观察局部组织学变化。术后14周处死剩余兔取材行EDTA脱钙，常规HE染色组织病理检查及统计学分析。结果植骨术后第3、7天病理示绝大部分植骨条坏死。2周显示有新生骨痂生长。4周骨折愈合率：植骨组为20%，对照组为7％。6周骨愈合率分别为60％和20％。8～12周骨折愈合率分别为87％和67％。组织病理学显示在骨折愈合的不同阶段均可见缺损部位的炎症灶内有新骨形成和对松质骨条的替代过程。感染率：植骨组为13％，对照组为7％。骨痂面积：治疗组明显优于对照组(P＜0．01)。结论 一期开放植骨是治疗感染性骨缺损的一种简便、有效的方法。     

Ⅰ期开放松质骨植骨治疗感染性骨缺损

目的：探讨Ⅰ期开放松质骨植骨治疗感染性骨缺损的可行性,总结提高治疗成功率的因素。方法：12例感染性骨缺损患者,男8例,女4例;年龄22～68岁,平均42岁。其中跟骨骨缺损7例,胫骨4例,股骨1例。采用患处换药,刮除失活的软组织及骨组织,清创后Ⅰ期行自体松质骨植骨,伤口开放,术后创面爬满肉芽后行游离植皮治疗。结果：术后移植骨质表面覆盖肉芽组织时间平均24.1d,创面完全闭合时间平均30.3d,所有患者经过8～30个月（平均18个月）随访,所有骨缺损处经植骨后均骨性愈合,未发现感染复发者。结论：Ⅰ期开放植骨术是治疗感染性骨缺损简单可行的方法,术前刮除失活组织,术中彻底清除肉芽组织、充分植入松质骨及术后严格无菌换药是手术成功的关键。     

Use of hydroxyapatite ceramics for treatment of nonunited osseous defect after open fracture of lower limbs

Introduction  

Osseous defects in nonunited open fracture of the lower limbs are difficult to treat. Autogenous bone grafting is a promising treatment options, but a finite amount of autogenous bone graft is available from each individual and donor site morbidity remains a problem. These limitations have prompted the development and use of synthetic biomaterials such as hydroxyapatite (HA) ceramics. However, little information is available regarding the challenging cases such as nonunited open fractures The purpose of the present study is to evaluate the outcomes associated with the treatment of osseous defects in nonunited open fracture using novel HA ceramics.     

骨髓基质成骨细胞-松质骨基质复合人工骨修复颅骨缺损的实验研究

目的 观察松质骨基质－骨髓基质成骨细胞复合工人骨在骨缺损区的成骨作用，探索该组织工程化人工骨修复颅骨缺损的可行性。方法 成年新西兰兔骨髓细胞体外培养、诱导后，接种于藻酸盐－松质骨基质中，形成松质骨基质－藻酸盐－骨髓基质成骨细胞复合人工骨，修复自体颅骨缺损。分别植入松质骨基质和骨髓基质成骨细胞作为对照。植入4周和8周后行X线摄片和组织学检查，观察骨形成情况。结果 复合人工成骨量优于单纯植入松质骨基持或骨髓基质成骨细胞组，并明显优于空白对照。结论 松质骨基质－骨髓基质成骨细胞复合人工骨髓修复颅骨缺损效果良好，可以作为临床大型骨缺损修复的途径之一。     

Qualitative and quantitative analysis of orthotopic bone regeneration by marrow

A rat model of a femoral segmental defect was used to specifically test the hypothesis that autogenous marrow has the osteogenic capability to heal a bone defect. The variables analyzed included the ratio of the marrow volume to the defect, implantation of live or dead marrow, and remodeling of established nonunions by implantation of live marrow. The uniqueness of this model allows biomechanical evaluation of the new bone formed by the implant. When live marrow was implanted, woven bone formed at 3 weeks, progressing to early lamellar bone at 6 weeks, with subsequent remodeling for as long as 12 weeks in a volumetric fashion (p < 0.05). Bone marrow, when placed in a fresh femoral defect and given in sufficient amounts, produced a rate of union comparable with that of autologous bone grafts. Mature lamellar bone formed by marrow was evaluated biomechanically: the results were statistically comparable with those of cancellous bone grafts at 12 weeks. Significant bone formation occurred when marrow was percutaneously injected in femoral nonunions, although union and remodeling did not take place in this rat model. Implantation of dead marrow resulted in rare cellular infiltration and minimal bone formation in a manner comparable with that of autogenous cancellous bone grafts. These results indicate that bone marrow can lead to structurally functional bone regeneration in an orthotopic location.     

A radiographical and biomechanical study of demineralized bone matrix implanted into a bone defect of rat femurs with and without bone marrow

Repair of large bone defects represents a challenge to orthopedic surgery since autogenous graft is not available in large amounts. Demineralized bone matrix (DBM) which contains bone morphogenic protein, a potent osteoinductive glycoprotein, and collagen, an osteoconductive matrix, may be an effective substitute for these graft materials. Bone marrow which contains osteoprogenitor cells could potentiate the osteoinductive and osteoconductive properties of demineralized bone matrix. This study tested the ability of demineralized bone matrix with and without bone marrow to bridge large segmental defects, and evaluated the results both radiographically and biomechanically as compared to autogenous (isogeneic) cancellous bone graft. Demineralized bone-matrix segments implanted into a plated femoral segmental defect in rats resulted in firm union in most animals. Bone marrow significantly enhanced bone formation of demineralized bone-matrix implants at an early stage but with time, differences between bone marrow-augmented and bone marrow-deprived demineralized bone implants were no longer demonstrable radiographically and biomechanically. Newly formed bone had about 50% of the strength of the contralateral control bones. Femurs implanted with cancellous bone isografts had similar evidence of absolute union rate, radiographic and mechanical properties as DBM-implanted femurs.     

The effect of various sterilization procedures on the osteoinductive properties of demineralized bone matrix]

To minimize potential infection following the transplantation of allogeneic bone, extremely rigorous selection of donors and careful processing and storage of samples are required. Other major problems related to allogeneic transplants, such as reduced osteogenic properties and immunological reactions, led to the development of demineralized bone matrix (DBM). This osteoinductive bone extract is largely free of antigens and is easy to produce. However, to eliminate the potential risk of infection, DBM should be sterilized prior to implantation. The purpose of this study was to investigate the influence of different sterilization techniques on the osteoinductive properties of DBM. A series of 76 cortical defects (drill holes) 0.6 cm in diameter in the tibiae of 11 Merino sheep were filled with DBM in addition to autogeneic and allogeneic cancellous bone. Prior to implantation DBM was sterilized by autoclaving, gamma irradiation, or application of ethylene oxide or ethyl alcohol. A further 12 drill holes were left empty as controls. The formation of new bone was examined 3 and 6 weeks postoperatively, using histological, fluorescent-optical and microradiographical techniques. The amount of newly formed bone was also quantified. Apart from autoclaved DBM all matrix grafts showed excellent new bone formation following sterilization, by far exceeding the formation with allogeneic cancellous bone.     

双相磷酸钙组织工程骨块重建股骨头内骨缺损的实验研究

目的 观察在体外构建的具有仿生结构的双相磷酸钙（biphasic calcium phosphate，BCP）组织工程骨块植入犬股骨头缺损内的骨再生情况及预防股骨头塌陷的效果。方法 以犬股骨头的松质骨样本Micro—CT（micro—computed tomography）图像为基础，提取其中的图像信息，利用三维凝胶叠层成形法制备出具有仿骨小梁结构的陶瓷支架。在体外利用诱导分化的自体骨髓间充质细胞与仿生BCP支架复合，构建组织工程骨块，将其植入10只犬的股骨头负重区骨缺损内；另取10只火作为对照组，在股骨头骨缺损区内打球植入自体松质骨粒，对比观察仿生BCP骨块的植入效果。结果 制备出的股骨头仿生BCP支架具有良好的三维空间结构，支架小梁具有一定的方向性，呈板状模型；细胞在支架表面大量生长。植入动物体内30周后，实验组火股骨头外形基本完整，新生骨质包绕支架小梁并沿支架表面生长，而对照组犬股坩头均出现不同程度的塌陷。结论 仿生BCP组织工程骨块具有良好的生物相容性，植入犬股骨头负曩区骨缺损后，能在一定程度上防止股骨头塌陷。     

Personal experiences in the reconstruction of trauma-induced bone defects

In this report an analysis of all patients treated with bone grafting in a 5-year period is given. Bone grafting was necessary in 8.4% of patients treated by osteosynthesis. Bone defects are seen mostly in the lower extremities. Malunion and nonunion are relatively frequent after fractures of the forearm and tibia. Contaminated fractures were seen in 32 patients. Before any osseous reconstruction, the defects of skin and soft tissues had to be closed and local infections treated. The period between accident and bone grafting ranged between 3 weeks and 1 1/2 years. Only in stage I fractures is primary grafting indicated. Intensive treatment of infection was required first in 16.9% of cases. When segmental defects are present, multistaged bone grafting entails only a low degree of risk and usually successful. In 87% autogenic cancellous iliac bone was transplanted. The use of allogenic spongiosa cannot be recommended for traumatic defects.     

Early prophylactic bone grafting of high-energy tibial fractures

Fifty-three high-energy tibial fractures treated with early prophylactic posterolateral bone grafting were retrospectively reviewed. The bone-grafting procedures were performed at a mean of ten weeks following injury and at a mean of eight weeks following soft-tissue coverage. Ninety-six percent of the fractures had associated injuries with a mean injury severity score of 20.9. Seventy-nine percent of the fractures were classified as Grade III open fractures, and 40% had bone loss greater than 50% of the cortical circumference. Ninety-six percent of the fractures healed at a mean time of 43 weeks after injury. Segmental bone loss and soft-tissue injury requiring flap coverage were the best predictors of prolonged time to union. Comparison with a matched historical control group of tibial fractures not receiving early bone grafts revealed a mean reduction in time to union of 11.7 weeks (p = 0.03). The incidence of chronic osteomyelitis was 1.9%. These results are attributed to early and repeated aggressive debridement, immediate rigid external fixation, early soft-tissue coverage, and early posterolateral bone grafting. Recommendations include posterolateral cancellous bone grafting two weeks following wound closure by delayed primary closure, split-thickness skin graft, or local rotational myoplasty. A six-week delay following freely vascularized soft-tissue coverage prior to bone grafting is suggested.     

Bone matrix and marrow versus cancellous bone in rabbit radial defects

Implants of demineralized bone matrix induce new bone formation. In order to estimate the possible clinical usefulness of this phenomenon, autologous cancellous bone grafts were compared with composite grafts of bone matrix and marrow. Cancellous bone from the tuber ischii of the rabbit was transplanted to a preformed radial defect in the same animal. On the opposite side, a similar defect was filled with a mixture of either allogenous or autogenous bone-matrix particles and autogenous bone marrow. After 25 days, calcium 45 was injected intravenously. Three days later the animals were killed. Standardized segments of the rabbit's forearms, containing the middle of the defect, were cut out, ashed, and analyzed for 45Ca activity. No side difference in 45Ca deposition was found. The callus ash weight of the allogenous matrix-transplanted side was approximately 60% of that of the cancellous bone side. This side difference of ash weights corresponds to the estimated initial mineral content of the cancellous graft. Nontransplanted defects had very low ash weight and 45Ca activity. Thus, in the rabbit, composite grafts of bone matrix and marrow produce a bone yield comparable to that of cancellous bone.