The effect of simvastatin on bone formation and ceramic resorption in a peri-implant defect model

Experimental use of statins as stimulators of bone formation suggests they may have widespread applicability in the field of orthopaedics. With their combined effects on osteoblasts and osteoclasts, statins have the potential to enhance resorption of synthetic materials and improve bone ingrowth. In this study, the effect of oral and local administration of simvastatin to a beta tricalcium phosphate (betaTCP)-filled defect around an implant was compared with recombinant human bone morphogenetic protein 2 (rhBMP2). On hundred and sixty-two Sprague-Dawley rats were assigned to treatment groups: local application of 0.1, 0.9 or 1.7 mg of simvastatin, oral simvastatin at 5, 10 or 50 mg kg(-1) day(-1) for 20 days, local delivery of 1 or 10 microg of rhBMP2, or control. At 6 weeks rhBMP2 increased serum tartrate-resistant acid phosphatase 5b levels and reduced betaTCP area fraction, particle size and number compared with control, suggesting increased osteoclast activity. There was reduced stiffness and increased mechanical strength with this treatment. Local simvastatin resulted in a decreased mineral apposition rate at 6 weeks and increased fibrous area fraction, betaTCP area fraction, particle size and number at 26 weeks. Oral simvastatin had no effect compared with control. Local application of rhBMP2 increased resorption and improved mechanical strength whereas simvastatin was detrimental to healing. Oral simvastatin was ineffective at promoting either ceramic resorption or bone formation. The effect of statins on the repair of bone defects with graft substitute materials is influenced by its bioavailability. Thus, further studies on the optimal delivery system are needed.     

Autogenous bone particle/titanium fiber composites for bone regeneration in a rabbit radius critical-size defect model

Purpose: To explore the effects of autogenous bone particle/titanium fiber composites on repairing segmental bone defects in rabbits. Materials and methods: A model of bilateral radial bone defect was established in 36 New Zealand white rabbits which were randomly divided into 3 groups according to filling materials used for bilaterally defect treatment: in group C, 9 animal bone defect areas were prepared into simple bilateral radius bone defect (empty sham) as the control group; 27 rabbits were used in groups ABP and ABP-Ti. In group ABP, left defects were simply implanted with autogenous bone particles; meanwhile, group ABP-Ti animals had right defects implanted with autogenous bone particle/titanium fiber composites. Animals were sacrificed at 4, 8, and 12 weeks, respectively, after operation. Results: Micro-CT showed that group C could not complete bone regeneration. Bone volume to tissue volume values in group ABP-Ti were better than group ABP. From histology and histomorphometry Groups ABP and ABP-Ti achieved bone repair, the bone formation of group ABP-Ti was better. The mechanical strength of group ABP-Ti was superior to that of other groups. Conclusions: These results confirmed the effectiveness of autologous bone particle/titanium fiber composites for promoting bone regeneration and mechanical strength.     

Biodegradation process of alpha-TCP particles and new bone formation in a rabbit cranial defect model

The purpose of the present study was to observe the biodegradation process of pure alpha-tricalcium phosphate (alpha-TCP) particles and to determine the efficacy of alpha-TCP as a space maintainer in a bone defect. We used 14 rabbits and prepared two cranial bone defects in each rabbit. One defect was left empty as a control, whereas the other was filled with alpha-TCP particles about 300 mum in diameter. Animals were sacrificed at 1 week, 4 weeks, and 8 weeks. The cranial bone was then embedded either in paraffin wax for the preparation of decalcified specimens, or in polyester resin for the preparation of nondecalcified specimens. All specimens were evaluated histologically and histomorphometrically. As a consequence of the degradation of alpha-TCP, a "reticulate structure" appeared in the particles at 1 week and new bone was observed in this structure at 8 weeks. The amount of new bone between the control and experimental groups was not significantly different at any of the time points. However, in the experimental group, new bone at the surface of alpha-TCP was evident even in the center of the defect whereas fibrous connective tissue was dominant in the control group. These results indicate that alpha-TCP is a degradable osteoconductive material that is able to act as a space maintainer for bone regeneration when applied to a bone defect. While there was no significant difference in total bone formation between the experimental and negative control groups, the space-maintaining and osteoconductive properties of the particles may result in more complete bone formation in longer-term studies.     

The bone formation in vitro and mandibular defect repair using PLGA porous scaffolds

Highly porous scaffolds of poly(lactide-co-glycolide) (PLGA) were prepared by solution-casting/salt-leaching method. The in vitro degradation behavior of PLGA scaffold was investigated by measuring the change of normalized weight, water absorption, pH, and molecular weight during degradation period. Mesenchymal stem cells (MSCs) were seeded and cultured in three-dimensional PLGA scaffolds to fabricate in vitro tissue engineering bone, which was investigated by cell morphology, cell number and deposition of mineralized matrix. The proliferation of seeded MSCs and their differentiated function were demonstrated by experimental results. To compare the reconstructive functions of different groups, mandibular defect repair of rabbit was made with PLGA/MSCs tissue engineering bone, control PLGA scaffold, and blank group without scaffold. Histopathologic methods were used to estimate the reconstructive functions. The result suggests that it is feasible to regenerate bone tissue in vitro using PLGA foams with pore size ranging from 100-250 microm as scaffolding for the transplantation of MSCs, and the PLGA/MSCs tissue engineering bone can greatly promote cell growth and have better healing functions for mandibular defect repair. The defect can be completely recuperated after 3 months with PLGA/MSCs tissue engineering bone, and the contrastive experiments show that the defects could not be repaired with blank PLGA scaffold. PLGA/MSCs tissue engineering bone has great potential as appropriate replacement for successful repair of bone defect.     

Bone formation on the apatite-coated zirconia porous scaffolds within a rabbit calvarial defect

Previously, a strong and bioactive ceramic scaffold consisting of a porous zirconia body coated with apatite double layers (fluorapatite (FA) as an inner layer and hydroxyapatite (HA) as an outer layer) was successfully fabricated. In this contribution, the authors investigate the in vivo performance of the engineered bioceramic scaffolds using a rabbit calvarial defect model. In particular, the porosity and pore size of the scaffolds are varied in order to observe the geometrical effects of the scaffolds on their bone formation behaviors. The scaffolds supported on a zirconia framework can be produced with an extremely high porosity (approximately 84-87%), while retaining excellent compressive strength (approximately 7-8 MPa), which has been unachievable in the case of pure apatite scaffolds (approximately 74% porosity with approximately 2 MPa strength).The experimental groups used in this study include three types of zirconia scaffolds coated with apatite; high porosity (approximately 87%) with large pore size (approximately 500- 700 microm): AZ-HL, high porosity (approximately 84%) with small pore size (approximately 150-200 microm): AZ-HS, and low porosity (approximately 75%) with large pore size (approximately 500-700 microm): AZ-LL, as well as one type of HA porous scaffold: low porosity (approximately 74%) with a large pore size (approximately 500-700 microm) for the purpose of comparison. The scaffolds prepared with dimensions of approximately 10 mm (diameter) x 1.2 mm (thickness) are grafted in rabbit calvaria defects. The histological sections are made at 4 and 12 weeks after surgery and immunohistochemical analyses are performed on the samples.All of the specimens show a good healing response without adverse tissue reactions. Good healing is shown at 4 weeks post-surgery with the ingrowth of new bone into the macropore-channels of the scaffolds. The newly formed bone amounts to approximately 19.9-24.2% of the initial defect area, depending on the scaffold type, but there is no statistical significance between the scaffold groups. However, the defects without the scaffolds (control group) show a significantly lower bone formation ratio (approximately 4.3%). At twelve weeks after surgery, the extent of new bone formation is more pronounced in all of the scaffold groups. All of the scaffold groups show significantly higher bone formation ratios (26.7-46.9%) with respect to the control without the graft. In the comparison between the scaffold groups, those with high porosities (AZ-HL and AZ-HS) exhibit significantly higher bone formation as compared to the scaffold with low porosity (AZ-LL).Based on the present in vivo test performed within a rabbit calvaria defect model, it is concluded that the apatite-coated zirconia scaffolds show good bone forming ability and are considered to be a promising scaffolding material for bone regeneration since they possess a high level of both mechanical and biological properties.     

Beta-TCP bone graft substitutes in a bilateral rabbit tibial defect model

The use of artificial bone graft substitutes has increased as the surgical applications widen and the availability of allograft bone decreases. The ideal graft substitute should reabsorb with time to allow and encourage new bone formation whilst maintaining its properties as an osteoconductive scaffold until it is no longer required. A potential disadvantage of some synthetic substitutes is their long dissolution time. Beta-tricalcium phosphates (beta-TCPs) have some advantages when compared to hydroxyapatite (HA), when used as a filler, in that it is more rapidly reabsorbed. Three commercially available and clinically used beta-TCP bone graft substitutes with the same chemistry (Vitoss, Osferion, Chronos) but with varying macro and microscopic characteristics were investigated using a bilateral tibial metaphyseal defect model in New Zealand white rabbits. When placed into tibial defects all three materials performed similarly in terms of mechanical properties of the healing defects. A decrease in properties was found at 12 weeks where implant resorption was nearly achieved while remodelling of the anteromedial cortex had yet to be completed. All materials were osteoconductive and supported new bone formation while implant resorption with time differed between materials. Vitoss resorbed faster than the other materials and is likely to differences in particle geometry, pore structure and interconnectivity.     

兔桡骨临界骨缺损模型的制备

背景：各种原因造成的骨折和骨缺损导致的骨不连一直是临床骨科修复的一大难题,相关产品质量的检验需要标准的骨缺损模型,然而骨缺损的临界长度至今仍无定论。 目的：建立兔桡骨骨缺损模型,以确定兔桡骨临界骨缺损长度。 方法：将18只雄性新西兰大白兔,随机分为6组,在双侧桡骨中段分别做12,13,14,15,16,17 mm的缺损,伤口缝合包扎但不固定。 结果与结论：大体标本和放射学观察显示,3个月内12,13,14,15,16 mm组的缺损均有修复完整的情况,但17 mm组无一例修复。组织学结果显示12,13,14,15,16 mm组缺损修复区有骨小梁与骨基质的形成、骨再生和再血管化、髓腔不同程度再通以及成骨细胞,17 mm组可见成骨细胞,破骨细胞,但未见骨再血管化和髓腔再通。故兔桡骨临界骨缺损长度为17 mm。     

Controlled electro-implementation of fluoride in titanium implant surfaces enhances cortical bone formation and mineralization

Previous studies have shown that bone-to-implant attachment of titanium implants to cortical bone is improved when the surface is modified with hydrofluoric acid. The aim of this study was to investigate if biological factors are involved in the improved retention of these implants. Fluoride was implemented in implant surfaces by cathodic reduction with increasing concentrations of HF in the electrolyte. The modified implants were placed in the cortical bone in the tibias of New Zealand white rabbits. After 4 weeks of healing, wound fluid collected from the implant site showed lower lactate dehydrogenase activity and less bleeding in fluoride-modified implants compared to control. A significant increase in gene expression levels of osteocalcin and tartrate-resistant acid phosphatase (TRAP) was found in the cortical bone attached to Ti implants modified with 0.001 and 0.01 vol.% HF, while Ti implants modified with 0.1% HF showed only induced TRAP mRNA levels. These results were supported by the performed micro-CT analyses. The volumetric bone mineral density of the cortical bone hosting Ti implants modified with 0.001% and 0.01% HF was higher both in the newly woven bone (<100 μm from the interface) and in the older Haversian bone (>100 μm). In conclusion, the modulation of these biological factors by surface modification of titanium implants with low concentrations of HF using cathodic reduction may explain their improved osseointegration properties.     

Repair of segmental long bone defect in rabbit femur using bioactive titanium cylindrical mesh cage

A segmental rabbit femur defect was repaired using an empty bioactive titanium (BAT) mesh cage. A 10mm long titanium mesh cage was positioned in the bony defect and reinforced by intramedullary fixation. The BAT surface was prepared by chemical and thermal treatment. Pure titanium cages were used as a control. Torsional stiffness of the BAT group at 4 weeks was approximately equal to, and at 8 weeks twice, that of the intact femur. Differences between the torsional stiffness of the control and BAT groups were significant at both time intervals. Histological examinations showed that woven bone appeared around the cage by 4 weeks and transformed to lamella bone by 8 weeks. New bone bonded to the BAT surface without an intervening layer. The BAT cage enhanced the bone repairing process and achieved faster repair of long bone segmental defects.     

Titania and titania-silica coatings for titanium: comparison of ectopic bone formation within cell-seeded scaffolds

The aim of this study was to compare titania (TiO(2))-coated, titania-silica (TiSi)-coated, and uncoated (cpTi) titanium fiber meshes as scaffolds for bone engineering. The scaffolds were loaded with bone marrow stromal cells and implanted subcutaneously in rats. Ectopic bone formation after 1, 4, and 12 weeks of implantation was evaluated using histology and histomorphometry. After 1 week of implantation, multiple patches of unorganized mineralizing tissue were seen in all implants. The amount of this bone-like tissue clearly increased from 1 to 4 weeks. Bone apposition occurred in direct contact with coated meshes, while a thin layer of unmineralized fibrous tissue was often observed surrounding cpTi mesh fibers. After 12 weeks, the structure of bone, with bone marrow-like tissue, was further matured and mesh fibers were embedded in lamellar bone. No statistical differences in the amount of mineralized bone were observed between scaffold types at any point of time. Only TiSi scaffolds showed further increase in bone area from 4 to 12 weeks (p < 0.01). A notable difference was that the sol-gel coatings resulted in enhanced initial bone contact and distribution of bone tissue, whereas uncoated implants showed bone formation mainly in the center of the scaffolds. In conclusion, TiO(2)-based sol-gel coatings may be used in tissue engineering to gain more uniform distribution of bone throughout titanium fiber mesh scaffolds.     

Development and characterization of a rabbit alveolar bone nonhealing defect model

The aim of this study was to develop an easily accessible and reproducible, nonhealing alveolar bone defect in the rabbit mandible. Twenty-four adult male New Zealand white rabbits underwent unilateral mandibular defect surgery. Two types of defect in the premolar/molar region were compared: (1) a 10-mm "full thickness" cylindrical defect removing both cortical plates and the intervening trabecular bone and tooth roots; (2) a 10-mm "partial thickness" cylindrical defect removing only the lateral bony cortex, trabecular bone, and tooth roots. Both types of defect were examined at 0, 8, and 16 weeks using histology and/or microcomputed tomography to determine the quality and quantity of bone formation. The partial thickness defect displayed significant bone fill at 8 weeks (86.9% +/- 10.8%), and complete regeneration of bony contours and bridging by 16 weeks. In contrast, the full thickness defect was never able to bridge itself and displayed no significant difference in bone regeneration between the 8-week (61.5% +/- 3.7%) and 16-week (55.1% +/- 18.5%) time points. These results indicate that a nonhealing defect can be created with a 10-mm bicortical cylindrical ostectomy placed in the premolar/molar region of the rabbit mandible, demonstrating the potential of this animal model as a test bed for mandibular biomaterials and tissue-engineering constructs.     

带血供肌瓣作为骨生长因子载体修复骨缺损实验模型的探讨与制备

目的：制备带血供肌瓣植入骨缺损的动物模型。方法：取６只新西兰大白鼠,随机分为３组,每组２只,一组用于制备前肢铸型标本,一组行前肢动脉乳胶灌注,另一组用于骨缺损模型制作。结果：兔前肢指深屈肌有一较恒定的桡动脉分支,肌支长度在２５ｍｍ左右。以该肌支为蒂制成带血供肌瓣通过皮下隧道可安全地转移至桡骨下段骨缺损处。结论：以带血供指深屈肌瓣转移至桡骨下段１０ｃｍ以上骨缺损处是检验其能否作为骨生长因子载体较理想的实验模型。     

Haversian remodeling in guided bone regeneration with calcium alginate film in circular bone defect model of rabbit

The objective of this study is to investigate the effect of bioabsorbable Calcium alginate film in guided bone regeneration by the study of Haversian remodeling. Circular bone defects of 5 mm diameter were created in the corners of mandibles in 35 rabbits. The defects were covered with calcium alginate film (CAF) served as the experimental group, or collagen membrane (CM) as the control group, respectively. Healing condition was analyzed with gross, histological and immunohistochemical studies after 1, 2, 4, 6 and 8 weeks. The experimental group appeared more and earlier Haversian remodeling and osteoinductive factors leading to better bone regeneration. The control group showed more macrophages, less and later Haversian remodeling, absorbed slowly, while collected fewer osteoinductive factors in the early stage. Calcium alginate film, which is a relatively cheaper material, provides better effect than the collagen membrane in bone regeneration, Haversian remodeling and quantity of osteoinductive factors.     

Porous calcium polyphosphate scaffolds for bone substitute applications in vivo studies

Porous rods (6 mm in length and 4 mm in diameter) of calcium polyphosphate (CPP) made by gravity sintering of particles in the size ranges of 45-105, 105-150. and 150-250 microm and with initial volume percent porosity in the range of 35-45% were implanted in the distal femur of New Zealand white rabbits. In an initial experiment, four rabbits implanted with rods made from coarse particles (150-250 microm) were sacrificed at each of the following time points: 2 days, 2 weeks, 6 weeks and 12 weeks. In a subsequent experiment, 10 rabbits were implanted with rods made by sintering 45-105 microm particles and another 10 were made by using particles of 105-150 microm. These rabbits were sacrificed at 6 weeks (five rabbits) and 1 year (five rabbits). No adverse reaction was found histologically at any time point in either experiment. These experiments show that CPP macroporous rods can support bone ingrowth and that between 12 weeks and 1 year, the amount of bones formed is equivalent to the natural bone volume found at similar sites. The degradation of the CPP material is inversely proportional to the original particle size and is rapid initially (within the first 6 weeks) and slows down thereafter. In conclusion, this material seems to promote rapid bone ingrowth and can be tailored to degrade at a given rate in vivo to some degree through appropriate selection of the starting particle size.     

Dense fibrillar collagen matrices sustain osteoblast phenotype in vitro and promote bone formation in rat calvaria defect

Two pure collagen materials were prepared from acidic collagen solutions at 5 and 40?mg/mL. Benefits of collagen concentration on bone repair were evaluated in vitro with human calvaria cells and in vivo in a rat cranial defect. Both materials exhibited specific structures, 5?mg/mL was soft with an open porous network of fibrils; 40?mg/mL was stiffer with a plugged surface and bundles of collagen fibrils. Osteoblasts seeded on 5?mg/mL formed an epithelioid layer with ultrastructural characteristics of mature osteoblasts and induced mineralization. Numerous osteoblasts migrated inside 5?mg/mL, triggering reorganization of their actin cytoskeleton, whereas on 40?mg/mL osteoblasts remained in a resting state. In rat calvaria defects, both materials induced active bone formation. Dual-energy X-ray absorption bone area measures after 4 weeks averaged 84.0% with 5?mg/mL, 88.4% with 40?mg/mL, and 36.7% in the controls (p?相似文献   

兔股骨髁临界性骨缺损动物模型制备及临界骨缺损值

文题释义：临界性骨缺损：首先定义为自然状况下骨缺损不进行任何处理无法自愈的最短的骨缺损尺寸。随后考虑到观察实验动物完整的生命周期是非常困难的,将临界性骨缺损值定义为在实验期间物种不能自行愈合的最短骨缺损尺寸。 动物模型：是在医学研究中建立的模拟人类疾病表现的动物,骨组织工程中建立临床相关的测试动物模型来研究材料的生物相容性、降解、力学性能以及与宿主组织的相互作用,是体外实验和人体临床试验之间的关键一步。 背景：兔股骨远端骨缺损模型被研究者们广泛用于骨缺损替代骨组织工程材料的测试,但对于兔股骨髁圆柱形骨缺损模型的大小文献报道不一,直径分布在5-9 mm,深度8-12 mm,目前尚无统一的标准。 目的：建立兔股骨髁不同尺寸骨缺损模型,确定兔股骨髁临界性骨缺损尺寸。 方法：6月龄雄性新西兰白兔18只,随机分为3组,每组各6只,分别建立骨缺损模型,骨缺损直径依次为5,6,7 mm,深度均为10 mm,双侧手术,共计12侧。分别于术后第1天及术后第4,8,12周行CT扫描及三维重建,CT-Hedberg评分评价骨缺损愈合情况;于术后12周处死新西兰白兔,取出股骨髁缺损样本,通过大体观察和苏木精-伊红染色分析缺损区愈合情况。实验方案经徐州医科大学实验动物道德伦理委员会批准。 结果与结论：①术后所有兔均存活,术后12周大体观察示：直径5 mm组缺损由新生骨组织充填,股骨髁塑形良好,骨缺损基本完全修复;直径6 mm组、直径7 mm组骨缺损区可见明显凹陷,新生骨组织较少,骨缺损未修复;②CT图像示：术后第4,8周,直径5 mm组缺损区逐渐减小,断端桥接;直径6 mm、直径7 mm组缺损区仅周边有少量新生骨长入,缺损面积较前稍减小;术后第12周可见直径5 mm组皮质骨结构完整、连续,骨缺损基本完全修复;直径6 mm组骨缺损部分修复;直径7 mm组缺损未修复,仍可见明显缺损空腔存在;③CT-Hedberg评分显示,术后各时间点直径6 mm组评分显著低于直径5 mm组(P < 0.05);与直径7 mm组比较差异无显著性意义(P > 0.05);④组织学结果示：术后12周直径5 mm组缺损区出现排列不规则的骨小梁结构,并可见大量新生骨组织填充,其他2组在骨缺损周边可见部分新生骨小梁存在,但缺损区新生骨组织填充较少;⑤结果说明,在12周的实验观察期内,在缺损深度同为10 mm的条件下,直径>6 mm的股骨髁缺损未能自行愈合,而直径<6 mm的股骨髁缺损基本完全修复。此结果符合临界骨缺损的标准,故直径6 mm可作为兔股骨髁临界骨缺损值。 ORCID: 0000-0002-1257-965X(徐石庄) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

In vivo evaluation of resorbable bone graft substitutes in a rabbit tibial defect model

Calcium sulfate as a bone graft substitute is rapidly resorbed in vivo releasing calcium ions but fails to provide long-term three-dimensional framework to support osteoconduction. The setting properties of calcium sulfate however allow it to be applied in a slurry form making it easier to handle and apply in different situations. This study examines the in vivo response of calcium sulfate alone and as a carrier for a coralline hydroxyapatite in an established bilateral corticocancellous defect model in rabbits. Defects were filled flush to the anterior cortex with a resorbable porous ceramic alone and in combination with calcium sulfate slurry, calcium sulfate slurry alone or calcium sulfate pellets and examined at time points up to 52 weeks. Specimens where assessed using Faxitron X-ray, light and electron microscopy. Calcium sulfate in either slurry or pellet form does indeed support new bone formation alone however, complete filling of the bone defect is not observed. Calcium sulfate in slurry form does however improve the surgical handling of particulate bone graft substitutes such as Pro Osteon 200 R, which remained as an osteoconductive scaffold for up to 52 weeks and may have played an important role in the ultimate closure of the cortical windows.     

Porous calcium polyphosphate scaffolds for bone substitute applications -- in vitro characterization

Porous structures were formed by gravity sintering calcium polyphosphate (CPP) particles of either 106-150 or 150-250 microm size to form samples with 30-45 vol% porosity with pore sizes in the range of 100 microm (40-140 microm). Tensile strength of the samples assessed by diametral compression testing indicated relatively high values for porous ceramics with a maximum strength of 24.1 MPa for samples made using the finer particles (106-150 microm). X-ray diffraction studies of the sintered samples indicated the formation of beta-CPP from the starting amorphous powders. In vitro aging in 0.1 M tris-buffered solution (pH 7.4) or 0.05 M potassium hydrogen phthalate buffered solution (pH 4.0) at 37 degreesC for periods up to 30d indicated an initial rapid loss of strength and P elution by 1 d followed by a more gradual continuing strength and P loss resulting in strengths at 30d equal to about one-third the initial value. The observed structures, strengths and in vitro degradation characteristics of the porous CPP samples suggested their potential usefulness as bone substitute materials pending subsequent in vivo behaviour assessment.     

Stromal cells promote bone invasion by suppressing bone formation in ameloblastoma

Aims: To study the stromal variation and role of stromal–tumour cell interaction in impaired bone formation as well as enhanced bone resorption in ameloblastoma. Methods and results: Four types of stroma were observed histologically; fibrous, desmoplastic, myxoid and myxoid with hyalinization. Osteoblast and osteoclast were counted using haematoxylin and eosin sections and immunohistochemistry with CD68. After histomorphometric analysis, only fibrous and myxoid types of stroma were distinctly identified. Secreted frizzled‐related peptide (sFRP)‐2, transforming growth factor‐beta 1 and receptor activator of nuclear factor‐κB ligand (RANKL) revealed strong expression in myxoid type compared with the normal stroma. Bone morphogenetic protein (BMP)‐2 was negative in myxoid type, but positive in normal stroma. Fibrous‐type stroma showed weak expression of all antigens except RANKL compared with myxoid type. Conclusions: The results suggest that stroma does not act only in bone resorption, but also in the suppression of new bone formation. sFRP‐2 is the main factor for impaired bone formation. The expression of markers related to osteoclastogenesis and suppression of osteoblast formation is higher in myxoid‐type than in fibrous‐type stroma. Tumour cells create a favourable environment for impaired bone formation by secreting sFRP‐2 as well as bone resorption by secreting RANKL and interleukin‐6.     

Bone formation in a long bone defect model using a platelet-rich plasma-loaded collagen scaffold

Platelet-rich plasma (PRP), a platelet concentrate made of autogenous blood, has been used in recent years to improve bone defect healing particularly in maxillofacial reconstructions. The aim of the present study was to assess the effect of PRP on new bone formation in a critical diaphyseal long bone defect. A critical size defect (2.5 cm) in the tibial diaphysis of 16 sheep was supplied either with autogenous PRP in a collagen carrier or with collagen alone (controls). Platelets were enriched about 3.5 fold compared to normal blood in the PRP. After 12 weeks, the explanted bone specimens were quantitatively assessed by X-ray, computed tomography (CT), biomechanical testing and histological evaluation. Bone volume, mineral density, mechanical rigidity and histology of the newly formed bone in the defect did not differ significantly between the PRP treated and the control group, and no effect of PRP upon bone formation was observed. It was suggested that PRP does not enhance new bone formation in a critical size defect with a low regenerative potential. Such bone defects might require more potent stimuli, e.g. combinations of functional biomaterials or autografts, precursor cells or osteoinductive growth factors.