Demineralized allogeneic bone matrix for cartilage repair

We tested the chondrogenic potential of demineralized allogeneic bone matrix (DABM) in the repair of osteochondral defects. In 42 adult rabbits, a 5-mm2 or 15-mm2 defect was created bilaterally in the intercondylar groove of distal femur. DABM was inserted directly in 37 defects, whereas in 35 it was inserted after previous placement in muscle for 4, 16, or 19 days. Another 12 defects were left empty, serving as controls. Subgroups of animals were killed at 6, 12, 18, and 26 weeks. The distal femora were excised and prepared for histologic evaluation in hematoxylin-eosin and toluidine blue. Cartilage-like repair tissue was observed in the majority of defects. However, there was a great variability in the experimental groups without any clear relationship to type of DABM implant, defect size, or postoperative time. Even individual knees exhibited varying stages of cartilage differentiation. Overall, DABM placed in muscle for 19 days appeared to yield the best repair of the defects. The most consistent findings of the present study were bone formation in the marrow of distal femur and, notably, the absence of bone differentiation toward the joint surface. Hence, it seems that the synovial environment prevents bone formation otherwise induced by DABM in vascular tissue. Although tissue formed in articular defects supplemented with DABM is of cartilaginous differentiation, which is retained over time, it is of highly variable quality. Hence, the described approach has to be optimized before it can be applied for the purpose suggested.     

The effect of locally delivered recombinant human bone morphogenetic protein-2 with hydroxyapatite/tri-calcium phosphate on the biomechanical properties of bone in diabetes-related osteoporosis

BackgroundRecombinant human bone morphogenetic protein-2 (rhBMP-2) is particularly effective in improving osteogenesis in patients with diminished bone healing capabilities, such as individuals with type 1 diabetes mellitus (T1DM) who have impaired bone healing capabilities and increased risk of developing osteoporosis. This study measured the effects of rhBMP-2 treatment on osteogenesis by observing the dose-dependent effect of localized delivery of rhBMP-2 on biomechanical parameters of bone using a hydroxyapatite/tri-calcium phosphate (HA/TCP) carrier in a T1DM-related osteoporosis animal model.ResultsAt the 4-week time point, the LD and HD groups both exhibited significantly higher BMD than controls; at the 8-week time point, the HD group exhibited significantly higher BMD than controls. Biomechanical testing revealed dose-dependent, higher trends in all parameters tested at the 4- and 8-week time points, with minimal significant differences.ConclusionsGroups treated with rhBMP-2 demonstrated improved bone mineral density at both 4 and 8 weeks compared to control saline groups, in addition to strong trends towards improvement of intrinsic and extrinsic biomechanical properties when compared to control groups. Data revealed trends toward dose-dependent increases in peak torque, torsional rigidity, shear stress, and shear modulus 4 weeks after rhBMP-2 treatment.

Level of evidence

Not applicable.     

Demineralized bone matrix and native bone morphogenetic protein in orthopaedic surgery

The recognition that demineralized bone matrix could induce bone formation when placed in mammalian skeletal muscle led to preclinical studies of crude native insoluble bone morphogenetic protein and noncollagenous protein, followed by the clinical application of demineralized bone matrix, chemosterilized autolyzed antigen-extracted allogenic bone, and autolyzed antigen-extracted allogenic bone matrix gelatin. Cultural norms and regulatory agencies influence the availability of different demineralized bone matrix preparations in different parts of the world, but there is continued interest in the biologic structure of native insoluble bone morphogenetic protein and noncollagenous protein aggregates and the applied science of osteoinduction and osteoconduction in reconstructive orthopaedic surgery. Demineralized bone matrix is not widely available in Asia, but tissue processing facilities in the United States distribute demineralized bone matrix materials with different carriers, handling properties, and possibly osteoinductive potential. The purpose of the current study was to review the development and use of various preparations of demineralized bone matrix materials.     

Demineralized bone matrix composite grafting for posterolateral spinal fusion

In a prospective series, the 24-month fusion status was evaluated radiographically among patients undergoing instrumented posterolateral lumbosacral spinal fusion. Seventy-three patients had a diagnosis of degenerative disk disease or degenerative spondylolisthesis and had supplemental bone grafting with demineralized bone matrix (DBM) putty (Grafton DBM; Osteotech, Eatontown, NJ) enriched with aspirated bone marrow (DBM bone marrow), DBM putty combined with iliac crest autograft (DBM autograft), or autograft. Overall, approximately 63% (12 of 19) of DBM bone marrow, 70% (19 of 27) of DBM autograft, and 67% (18 of 27) of autograft patients were fused at 24 months (P = .875). These findings suggest that both DBM composites offer similar performance to autograft in posterolateral spinal fusion.     

Demineralized bone matrix: basic science and clinical applications

Bone grafting with demineralized bone matrix (DBM) is useful in reconstructive surgery to ultimately provide anatomic alignment, restore function, or augment/change the biomechanics of the foot and ankle. DBM should be used in conjunction with a transplant or implant displaying mechanical strength. DBM can augment cortical grafts used for bridging gaps or defects and lengthening procedures by increasing the connectivity of the structural graft with the host bone. Another useful application is providing a biologic boost to patients who have less-than-ideal physiology. Because DBM has higher concentrations of available bone morphogenic proteins, it can aid in the incorporation of other grafts. Other uses include delayed unions, nonunions, packing joints for arthrodesis, filling resected cysts, and filling gaps of debrided infected bone.     

脱钙冻干异体骨移植对骨缺损的修复作用

目的应用脱钙冻干异体骨（DFDBA）修复骨缺损，解决种植区的骨量不足问题。方法在种植外科中，将脱钙冻干异体骨用于19例种植区骨缺损患者，观察种植体动度、牙齿指数（GI）及x线改变等临床指标，评价其临床应用效果。结果19例植骨手术均获成功，无一例种植体周围炎发生，种植体初期稳定性良好。结论脱钙冻干异体骨既有一定的力学支持能力，又有骨诱导作用，且可塑性强。     

Preparation and degradation characteristic study of bone repair composite of DL—polylactic acid／hydroxyapatite／decalcifying bone matrix

Objective:To explore the preparative method and study the degradation characteristics of bone repair composite of DL-polyactic acid(PDLLA) /hydroxyapatite(HA)/decalcifying bone matrix(DBM) in vitro.Methods:An emulsion blend method was developed to prepare the composite of PDLLA/HA/DBM in weight ratio of PDLLA:HA:DBM=1.2-2:1.5:1.The dynamic changes of weight,biomechanical property and pH value of PDLLA/HA/DBM and PDLLA in phosphate buffered saline(PBS,pH7.4)were studied respectively through degradation tests in vitro.Results:Without being heated,PDLLA,HA and DBM could be synthesized with the emulsion blend method as bone composite of PDLLA/HA/DBM,wich had both osteoconductive and osteoinductive effects.The diameter of the aperture was 100-400μm and the gap rate was 71.3%.During degradation,the pH value of PDLLA solution decreased lightly within 2 weeks,but decreased obviously at the end of 4 weeks and the value was 4.0 .While the pH value of PDLLA/HA/DBM kept quite steady and was 6.4 at the end of 12 weeks.The weight of PDLLA changed little within 4 weeks,then changed obviously and was 50% of its initial weight at the end of 12 weeks.While the weight of PDLLA/HA/DBM changed little within 5 weeks ,then changed obviously and was 60% of the initial weight at the end of 12 weeks.The initial biomechanical strength of PDLLA was 1.33 MPa, decreased little within 3 weeks, then changed obviously and kept at 0.11 MPa at the end of 12 weeks.The initial biomechanical strength of PDLLA/HA/DBM was 1.7 MPa, decreased little within 4 weeks, then changed obviously and kept at 0.21 MPa at the end of 12 weeks.Conclusions:The emulsion blend method is a new method to prepare bone repair materials.As a new bone repair material,PDLLA/HA/DBM is more suitable for regeneration and cell implantation,and the environment during its degradation is advantageous to the growth of bone cells.     

Demineralized bone matrix and fat autograft in a rabbit model of frontal sinus obliteration.

OBJECTIVE: In this study, we investigate the efficacy of demineralized bone matrix (DBM) as a material for frontal sinus obliteration in a rabbit model. STUDY DESIGN AND SETTING: Twenty-four New Zealand White rabbits were divided into four groups, and the study was carried out to two time periods. Twelve rabbits underwent frontal sinus obliteration with fat autograft, and 12 rabbits underwent the procedure with DBM. At 12 weeks, six control and six study rabbits were killed. The remaining 12 rabbits were killed at 36 weeks. All specimens underwent radiologic evaluation with spiral CT followed by histologic examination for evidence of bony growth. RESULTS: Sinuses obliterated with DBM showed replacement of the sinus cavity by trabecular bone. Histology demonstrated significant progressive replacement of DBM by cancellous bone from 12 weeks (53.3%) to 36 weeks (78.8%). There were no complications observed as a result of the materials used. CONCLUSION AND SIGNIFICANCE: DBM is a prospective material for frontal sinus obliteration. Long-term studies and human trials will further elucidate the role of this material.     

Comparative study of porous hydroxyapatite and tricalcium phosphate as bone substitute

This study was performed to quantitate the bone ingrowth and biodegradability of porous calcium phosphate. Two kinds of coralline hydroxyapatite (CHA), along with sintered tricalcium phosphate (TCP), were evaluated. All implants had totally interconnecting pores. These pores measured 260-600 mu for CHA-Goniopora (CHAG), 190-230 microns for CHA-Porites (CHAP), and 100-300 microns for TCP. Cylindrical implants (3 mm in diameter by 8 mm in length) were implanted into the diaphyses of rabbit tibias for 3 to 24 weeks. The quantity of regenerated bone, remaining implant, nonmineralized space, and the middle two quarters of the cortical area were measured by a computerized operator-assisted analysis for bone histomorphometry. At 3 weeks after implantation, 17.3% of CHAG, 11.3% of CHAP, and 7.0% of TCP were infiltrated by regenerated bone. At 24 weeks, 56.1% of CHAG, 52.7% of CHAP, and 44.7% of TCP were occupied by lamellar-type bone. Implant degradation was noted to be 46.4% for TCP and 27.5% for CHAP. In contrast, CHAG did not show appreciable degradation until 24 weeks.     

Accelerating bone formation and earlier healing after using demineralized bone matrix for limb lengthening in rabbits.

We studied the effects of grafting with demineralized bone matrix during lengthening of the tibia in young Japanese White rabbits. The demineralized bone matrix was made from frozen cortical bone harvested from other rabbits. A 5-mm gap was created in the tibial diaphysis by a subperiosteal osteotomy; a maximum of 20 mm (2-3 mm/day) of tibial lengthening was reached in a week with use of an external fixator. The control group of 20 rabbits did not receive an implant; the group of 21 experimental rabbits received an implant of demineralized bone matrix in the surgical gap. The control group failed to demonstrate radiographic callus 5 weeks after surgery, and nonunion was persistent after 1 year. In the group with demineralized bone matrix, new radiodensity was demonstrated within the lengthening gap at 3 weeks, with a gradual increase in bone density to 85% that of the intact tibia after 12 weeks. Bone union was seen within 1 year for all experimental animals for whom the external fixator was removed 8 weeks after the procedure. These bones showed normal bone structure histologically. The lengthening was carried out at a rapid distraction rate of 2-3 mm/day; therefore, this method allows for satisfactory bone formation at a faster rate than normal.     

Chondroosteogenetic response to crude bone matrix proteins bound to hydroxyapatite

For the development of a new implantable biomaterial that possesses osteogenetic ability, bone matrix morphogenetic proteins were bound to hydroxyapatite (BMP-HAP). A crude protein extract including the bone morphogenetic protein (BMP) fraction was precipitated in the pores of hydroxyapatite (HAP) inside of a dialysis sac. In tissue culture, BMP-HAP or HAP was used as substratum for rat mesenchymal muscle cell explants. The BMP-HAP and HAP controls were also implanted in the muscle pouches of mice. New cartilage and/or new bone formation was observed on the exterior surface of BMP-HAP but not of HAP controls. Implantation of this HAP into bone marrow cavities of rabbit femoral and tibial condyle produced new bone formation. The deposits extended further inside BMP-HAP than HAP pores. The pore diameters of 90-200 microns produced earlier ingrowth than into larger pore sizes. BMP-HAP should be tested for clinical application as osteogenetic biomaterial for augmentation of bone regeneration.     

Parecoxib impairs early metaphyseal bone healing in rats

Introduction Cox2 inhibitors decrease prostaglandin production and therefore influence bone healing especially in unstable long bone models. It is unclear to what extent implant fixation in stable metaphyseal bone is impaired. Method Male rats numbering 30 and female rats numbering 40 received a stainless steel screw in the metaphyseal bone of the proximal tibia. Half of the rats were treated with 6.4 mg/kg BW parecoxib by continuous release from a subcutaneous mini pump during 7 or 14 days. After treatment, the pull out force, stiffness, and pull out energy of the screw were measured. Results No effect of parecoxib on the pull out force was found for male rats. In female rats the pull out force was decreased by 16% (P = 0.03) after 7 days treatment with parecoxib. This effect had disappeared after 14 days. Conclusion Adverse effects of parecoxib on the early phase healing of metaphyseal bone in female rats are small and were not detectable after 14 days. No effect was seen in male rats, possibly due to a faster metabolic elimination of the drug.     

Demineralized bone implants for nonunion fractures, bone cysts, and fibrous lesions.

Demineralized bone implants were used to treat eight patients with fracture nonunion, five patients with bone cysts, and eight patients with fibrous lesions. Five of the eight patients with nonunions had had previous unsuccessful attempts at reconstruction. After fixation and implantation with either human or bovine demineralized bone, all eight fractures healed. For those patients with nonunion fractures, mean followup time was 8 years, 5 months, and longest followup was 15 years, 3 months. The cystic lesions in five patients included three typical aneurysmal bone cysts and two recurrent unicameral bone cysts. The aneurysmal bone cysts had excellent healing and bone remodeling. The two unicameral bone cysts were repacked more densely after 1 year and healed. For these patients with bone cysts, the mean followup time was 12 years, 5 months, and longest followup was 15 years, 1 month. The various fibrous lesions in seven of the eight patients were healed within 6 months, with only one requiring repacking. For these patients with fibrous bone lesions, the mean followup time was 9 years, 8 months, and longest followup was 14 years. A biopsy of the lesions in five patients was performed and in two cases showed osteoblasts and new bone around small particles of the implants. These results with long term followup show that allogeneic or xenogeneic demineralized bone implants offer a reasonable alternative for the treatment of typical nonunion fractures, bone cysts, and fibrous lesions of bone.     

脱矿骨纤维植入融合术治疗腰椎退行性疾病

[目的]探讨脱矿骨纤维(DBF)作为椎间融合器填充材料应用于下腰椎退行性疾病后路切开减压植骨融合内固定手术的临床疗效。[方法]回顾性分析2013年1月～2017年12月本院应用椎弓根钉内固定系统与椎间融合器技术治疗腰椎退行性疾病的患者69例。其中,28例使用DBF作为椎间融合器填充材料,41例完全采用自体骨填充。采用日本骨科学会(JOA)评分和Oswestry功能障碍指数(ODI)评价临床疗效,影像学检查评价植骨融合效果。[结果]两组患者均顺利手术,无严重并发症。DBF组27例患者术后未见过敏反应、感染或中毒症状,无皮疹、高热。两组患者术后平均随访(21.82±6.43)个月。两组术后JOA评分与ODI指数均较术著改善,差异有统计学意义(P0.05),术后第3、6个月DBF组JOA评分低于自体骨组,差异有统计学意义(P0.05),术后6个月,两组ODI指数差异无统计学意义(P0.05)。末次随访时两组间JOA和ODI评分差异均无统计学意义(P0.05)。影像学方面,术后3、6个月DBF组融合率低于自体骨组,差异有统计学意义(P0.05),但末次随访时,两组间融合率的差异无统计学意义(P0.05)。[结论]脱矿骨纤维作为植骨融合材料用于下腰椎退行性疾病手术治疗疗效满意,但较自体骨融合时间延长。     

Evaluation of hydroxyapatite and beta-tricalcium phosphate mixed with bone marrow aspirate as a bone graft substitute for posterolateral spinal fusion

Background:

Autologous cancellous bone is the most effective biological graft material. However, harvest of autologous bone is associated with significant morbidity. Since porous hydroxyapatite and beta-tricalcium phosphate are biodegradable materials and can be replaced by bone tissue, but it lacks osteogenic property. We conducted a study to assess their use as a scaffold and combine them with bone marrow aspirate for bone regeneration using its osteogenic property for posterolateral spinal fusion on one side and autologous bone graft on the other side and compare them radiologically in terms of graft incorporation and fusion.

Materials and Methods:

Thirty patients with unstable dorsal and lumbar spinal injuries who needed posterior stabilization and fusion were evaluated in this prospective study from October 2005 to March 2008. The posterior stabilization was done using pedicle screw and rod assembly, and fusion was done using hydroxyapatite and beta-tricalcium phosphate mixed with bone marrow aspirate as a bone graft substitute over one side of spine and autologous bone graft obtained from iliac crest over other side of spine. The patients were followed up to a minimum of 12 months. Serial radiographs were done at an interval of 3, 6, and 12 months and CT scan was done at one year follow-up. Graft incorporation and fusion were assessed at each follow-up. The study was subjected to statistical analysis using chi-square and kappa test to assess graft incorporation and fusion.

Results:

At the end of the study, radiological graft incorporation and fusion was evident in all the patients on the bone graft substitute side and in 29 patients on the autologous bone graft side of the spine (P > 0.05). One patient showed lucency and breakage of distal pedicle screw in autologous bone graft side. The interobserver agreement (kappa) had an average of 0.72 for graft incorporation, 0.75 for fusion on radiographs, and 0.88 for the CT scan findings.

Conclusion:

Hydroxyapatite and beta-tricalcium phosphate mixed with bone marrow aspirate seems to be a promising alternative to conventional autologous iliac bone graft for posterolateral spinal fusion.