Denaturation of demineralized bone matrix significantly reduces bone formation by guided tissue regeneration

AIM: To examine in a discriminating capsule model whether denaturation of demineralized bone matrix (DBM) by heating may influence bone formation. MATERIALS AND METHODS: DBM was produced from the long bones of rats. Half the portion of DBM was denatured by heating in distilled water for 20 min at temperatures between 70 degrees C and 90 degrees C. Prior to the study, the destruction of the osteoinductive properties of the DBM was confirmed in three rats following intramuscular implantation. Thirty, 4-month-old, male albino rats of the Wistar strain were used in the study. Following surgical exposure of the mandibular ramus, a hemispherical Teflon capsule (internal diameter = 5.0 mm) was placed, with its open part facing the lateral aspect of the ramus. On one side (test side), the capsule was loosely packed with denatured DBM, while on the contralateral side, serving as control, the capsule was loosely packed with the same amount of non-denatured DBM. After healing periods of 30, 60, and 120 days, groups of 10 animals were killed and 40-70 microm thick undecalcified sections of the capsules were produced. Three sections from each specimen, representing the mid-portion of the capsule, were subjected to histological analysis and computer-assisted planimetric measurements. RESULTS: Increasing amounts of newly formed bone were observed in both test and control capsules during the experimental period. At 4 months, the new bone formed in the control capsules occupied 46.7% of the cross-sectional area of the capsules, while it was only 19.1% in the test capsules (P<0.05). CONCLUSION: Denaturation of DBM by heating significantly reduces bone formation by guided tissue regeneration.     

钛膜引导骨生长保持牙槽骨骨量的临床研究

目的评价钛膜在拔牙后引导骨生长保持牙槽骨骨量的临床效果，并探讨其应用技巧。方法选取62例只拔除1颗前牙的病例，随机分为3组，第1组（21例）为对照组，拔牙后3～4个月回院接受种植牙手术，第2组（20例）为钛膜组，拔牙后牙槽窝经过修整，放置稍大于牙槽窝的纯钛膜并将周围组织拉拢缝合。5～6个月回院接受种植牙手术或钛膜取出手术。第3组（21例）为钛膜加人工骨组．拔牙后牙槽窝即刻填入人工骨并放置稍大于牙槽窝的纯钛膜并缝合．5～6个月回院接受种植牙手术或钛膜取出手术。在曲面断层片上测量牙槽骨高度的变化。以上各组分别于拔牙后1、2、3及6个月后进行牙槽骨密度的测量。结果在拔牙后5～6个月时，牙槽骨平均退缩率分别为（26．42±0．89）％，（14．71±0．92）％，（7．434±0．76）％。第1、2组间差异具有统计学意义（P〈0．01）；在术后1～2个月时．第2、3组牙槽窝骨密度均高于第1组（P〈0．01）。结论钛膜可以有效保持拔牙后牙槽骨骨量．部分病例有拔牙创未能关闭及早期裂开现象，适当处理，未明显影响新生骨形成。     

可吸收性引导骨再生胶原膜治疗骨缺损的实验研究

本研究是对国产吸收性胶原膜的骨引导再生,在骨缺损上应用的有效性方面进行实验研究。方法在实验动物成年犬的颌骨左右侧形成骨缺损,实验侧的骨缺损上覆盖吸收性胶原膜,对照侧没有覆盖,实验期间分别为２周、６周、１２周的取出下颌骨;     

Biomimetic surface modification using synthetic oligopeptides for enhanced guided bone regeneration in beagles

Background: In previous studies, oligopeptide corresponding to the cell‐binding domains of bone morphogenetic proteins that bind to bone morphogenetic protein receptor enhanced the bone regenerative capacity of bovine bone minerals (BBM). The aim of this study is to evaluate the ability of BBM coated with oligopeptide to promote periodontal regeneration in a 1‐wall intrabony defect model in dogs. Methods: The second and third mandibular premolars and first molars of six adult beagles were extracted bilaterally, and the extraction sites were allowed to heal for 10 weeks. The 1‐wall intrabony defects were prepared bilaterally on the mesial and distal side of the fourth mandibular premolars. Twenty‐four intrabony defects were assigned to four treatment groups: 1) open flap debridement; 2) guided tissue regeneration (GTR); 3) GTR with a collagen membrane and BBM; and 4) GTR with a collagen membrane and BBM coated with the oligopeptide (Pep‐BBM). The animals were sacrificed 10 weeks after surgery. For the histometric analysis, defect height, junctional epithelium migration, new cementum, new bone height, and new bone area were measured. New bone volume was measured using microcomputed tomography. Results: Wound healing was generally uneventful. For junctional epithelium migration, the BBM and Pep‐BBM groups exhibited mean (± SE) values of 0.53 ± 0.41 and 0.48 ± 0.30 mm, and for new cementum height, 1.71 ± 0.46 and 2.50 ± 2.00 mm, respectively. For junctional epithelium migration and cementum regeneration, there were no significant differences between the two groups. The mean (± SE) values of new bone height and new bone volume in the Pep‐BBM group (3.88 ± 0.31 mm and 32.35% ± 9.60%) were significantly greater than the mean values for the BBM group (2.60 ± 0.41 mm and 20.56% ± 1.89%). For bone regeneration, the Pep‐BBM group showed superior results compared to the BBM group with statistically significant differences. Conclusions: Through various parameters to evaluate periodontal regeneration, this oligopeptide coating influenced only the ability of BBM to promote bone regeneration in 1‐wall intrabony defects in beagles. Junctional epithelium migration and cementum regeneration were not affected by this oligopeptide coating, and further investigations with special focus on regeneration of the periodontal ligament are necessary.     

引导洞形骨缺损再生模型中的哈弗氏管

目的 观察可吸收性海藻酸钙膜引导骨再生过程中哈弗氏管的再建及意义。方法 在家兔双侧下颌角前切迹处形成骨缺损。实验侧骨缺损上覆盖海藻酸钙膜，对照侧覆盖胶元膜。分别在术后1、2、4、6、8周时取出下颌骨，进行大体观察，X线观察，组织学观察，TGF-β与VEGF免疫组化染色。结果 海藻酸钙膜4周-6周吸收，胶元膜6周-8周吸收；前者异物巨噬细胞反应程度轻，后者反应程度重；术后6周内实验组哈弗氏管比对照侧出现早而多；前者大体观骨缺损愈合表面平整，后者表面突起；术后4周内实验侧TGF-β与VEGF阳性明显强于对照侧。结论 海藻酸钙膜比较元膜效果更好，哈弗氏系统再建和成骨作用均更快，且不影响骨再生修复。     

生长因子在牙槽骨组织再生中的应用与研究进展

实现牙槽骨组织再生是口腔医学领域的热门研究方向。许多国内外研究表明,生长因子在牙槽骨组织再生中起到重要作用,无论是在口腔种植,牙周治疗,还是拔牙位点保存等多个领域均有广阔的应用前景。本文对生长因子在口腔领域中促进牙槽骨组织再生的应用及研究进展进行综述。     

Alveolar bone formation at dental implant dehiscence defects following guided bone regeneration and xenogeneic freeze-dried demineralized bone matrix.

The present study evaluated rate and extent of alveolar bone formation in dental implant dehiscence defects following guided bone regeneration (GBR) and implantation of xenogeneic freeze-dried demineralized bone matrix (xDBM). A total of 16 titanium plasma-sprayed (TPS) and 16 hydroxyapatite-coated (HA) titanium cylinder implants were inserted in 4 mongrel dogs following extraction of the mandibular premolar teeth. Four implant sites per jaw quadrant (2 TPS and 2 HA implant sites) were prepared into extraction sockets in each dog. Buccal alveolar bone was removed to create 3 x 5 mm dehiscence defects. Two jaw quadrants in separate animals received GBR, GBR + xDBM, xDBM (control), or gingival flap surgery alone (GFS; control). Thus, four conditions were available for each implant type (TPS or HA): GBR, GBR + xDBM; xDBM and GFS. The animals received fluorescent bone labels to allow observations of rate and extent of bone formation. Animals were sacrificed at 12 weeks postsurgery and block sections were harvested for histologic analysis. There were no apparent histologic differences between TPS and HA implant defects. GBR and GBR + xDBM resulted in almost complete bone closure of the dental implant dehiscence defect. Rate of bone formation appeared higher following GBR alone. Extent of bone formation appeared somewhat greater following GBR + xDBM; however, delayed. xDBM alone did not adequately resolve the bony defect. In conclusion, GBR results in rapid, clinically relevant bone closure of dental implant dehiscence defects. Adjunctive implantation of xDBM does not appear to significantly improve the healing response in the model used.     

Immunolocalization of markers for bone formation during guided bone regeneration in osteopenic rats

Objective

The aim of this paper was to evaluate the repair of onlay autogenous bone grafts covered or not covered by an expanded polytetrafluoroethylene (e-PTFE) membrane using immunohistochemistry in rats with induced estrogen deficiency.

Material and Methods

Eighty female rats were randomly divided into two groups: ovariectomized (OVX) and with a simulation of the surgical procedure (SHAM). Each of these groups was again divided into groups with either placement of an autogenous bone graft alone (BG) or an autogenous bone graft associated with an e-PTFE membrane (BGM). Animals were euthanized on days 0, 7, 21, 45, and 60. The specimens were subjected to immunohistochemistry for bone sialoprotein (BSP), osteonectin (ONC), and osteocalcin (OCC).

Results

All groups (OVX+BG, OVX+BMG, SHAM+BG, and SHAM+BMG) showed greater bone formation, observed between 7 and 21 days, when BSP and ONC staining were more intense. At the 45-day, the bone graft showed direct bonding to the recipient bed in all specimens. The ONC and OCC showed more expressed in granulation tissue, in the membrane groups, independently of estrogen deficiency.

Conclusions

The expression of bone forming markers was not negatively influenced by estrogen deficiency. However, the markers could be influenced by the presence of the e-PTFE membrane.     

富自体浓缩生长因子纤维蛋白液联合Bio-Oss骨粉对口腔种植引导性骨再生术后黏膜愈合和骨缺损再生的影响

目的 探讨富自体浓缩生长因子纤维蛋白液联合Bio-Oss骨粉对口腔种植引导性骨再生术后黏膜愈合和骨缺损再生的影响。方法 选择2016年10月—2018年12月濮阳市油田总医院口腔科接诊的83例上颌单个前牙缺失伴唇侧骨缺损患者,将其分为2组,实验组（42例）采用富自体浓缩生长因子纤维蛋白液+Bio-Oss骨粉引导骨再生,对照组（41例）采用Bio-Oss骨粉引导骨再生。随访2组患者术后7 d、6周、1年手术区黏膜愈合程度、种植体成功率、骨缺损再生情况、疼痛程度和其他并发症等的发生情况。观察2组种植体成功率和术后并发症,以及术后黏膜颜色、肿胀程度、出血指数、探诊深度、附着丧失、植骨高度、成骨厚度的差异。采用SPSS 25.0软件包对数据进行统计学分析。结果 2组种植体成功率无统计学差异（95.24% ∶ 97.56%,P>0.05）,实验组并发症发生率显著低于对照组（2.38% ∶ 14.63%,P<0.05）,实验组黏膜颜色、肿胀度评分显著低于对照组[（0.65±0.03）分 ∶ （2.01±0.15）分、（1.10±0.37）分 ∶ （2.69±0.54）分,P<0.05],出血指数、探诊深度、附着丧失显著低于对照组[（0.35±0.05） ∶ （0.49±0.09）、（3.39±0.62）mm ∶ （4.41±0.95）mm、（3.02±0.66）mm ∶ （5.31±0.91）mm,P<0.05],植骨高度、成骨高度显著高于对照组[（2.61±0.50）mm ∶ （2.20±0.31）mm、（2.53±0.34）mm ∶ （2.02±0.27）mm,P<0.05],实验组术后疼痛程度显著低于对照组（P<0.05）。结论 富自体浓缩生长因子纤维蛋白液联合Bio-Oss骨粉可有效促进口腔种植引导骨再生术后黏膜愈合和骨缺损再生,减轻术后疼痛和并发症。     

Alveolar bone formation at dental implant dehiscence defects following guided bone regeneration and xenogeneic freeze‐dried demineralized bone matrix

The present study evaluated rate and extent of alveolar bone formation in dental implant dehiscence defects following guided bone regeneration(GBR) and implantation of xenogeneic freeze‐dried demineralized bone matrix (xDBM). A total of 16 titanium plasma‐sprayed (TPS) and 16 hydroxyapatite‐coated (HA) titanium cylinder implants were inserted in 4 mongrel dogs following extraction of the mandibular premolar teeth. Four implant sites per jaw quadrant (2 TPS and 2 HA implant sites) were prepared into extraction sockets in each dog. Buccal alveolar bone was removed to create 3 x 5 mm dehiscence defects. Two jaw quadrants in separate animals received GBR, GBR+xDBM, xDBM (control), or gingival flap surgery alone (GFS; control). Thus, four conditions were available for each implant type (TPS or HA): GBR, GBR+xDBM; xDBM and GFS. The animals received fluorescent bone labels to allow observations of rate and extent of bone formation. Animals were sacrificed at 12 weeks postsurgery and block sections were harvested for histologic analysis. There were no apparent histologic differences between TPS and HA implant defects. GBR and GBR+xDBM resulted in almost complete bone closure of the dental implant dehiscence defect. Rate of bone formation appeared higher following GBR alone. Extent of bone formation appeared somewhat greater following GBR+xDBM; however, delayed. xDBM alone did not adequately resolve the bony defect. In conclusion, GBR results in rapid, clinically relevant bone closure of dental implant dehiscence defects. Adjunctive implantation of xDBM does not appear to significantly improve the healing response in the model used.     

富含血小板血浆与口腔种植骨再生

富含血小板血浆因含多种高浓度生长因子而对骨再生有促进作用。本文综述了富含血小板血浆在促进口腔种植骨再生的研究进展。     

Prognostic factors for alveolar regeneration: bone formation at teeth and titanium implants

OBJECTIVES: There is a limited understanding of the effect of defect characteristics on alveolar bone healing. The objectives of this study were to assess the effect of alveolar bone width and space provision on bone regeneration at teeth and titanium implants, and to test the hypothesis that the regenerative potentials at teeth and implants are not significantly different. METHODS: Critical size, 5-6-mm, supra-alveolar, periodontal defects were surgically created in 10 young adult dogs. Similarly, critical size, 5-mm, supra-alveolar, peri-implant defects were created in four dogs. A space-providing expanded polytetrafluoroethylene device was implanted for guided tissue regeneration/guided bone regeneration. The animals were euthanized at 8 weeks postsurgery. Histometric analysis assessed alveolar bone regeneration (height) relative to space provision by the device and the width of the alveolar crest at the base of the defect. Statistical analysis used the linear mixed models. RESULTS: A significant correlation was found between bone width and wound area (r=0.55892, p<0.0001). Generally, bone width and wound area had statistically significant effects on the extent of bone regeneration (p<0.0005 and p<0.0001, respectively). Bone regeneration was linearly correlated with the bone width at periodontal (p<0.001) and implant (p=0.04) sites, and with the wound area at periodontal (p<0.0001) and implant (p=0.03) sites. The relationships of bone regeneration with these two variables were not significantly different between teeth and implants (bone width: p=0.83; wound area: p=0.09). When adjusted for wound area, bone regeneration was significantly greater at periodontal than at implant sites (p=0.047). CONCLUSIONS: The horizontal dimension of the alveolar bone influences space provision. Space provision and horizontal dimension of the alveolar bone appear to be important determinants of bone regeneration at teeth and implants. The extent of alveolar bone formation at implant sites is limited compared with that at periodontal sites.     

Bio-Oss骨粉联合富血小板纤维蛋白在牙槽骨缺损种植引导骨再生后的骨量变化

目的：探讨Bio-Oss骨粉联合富血小板纤维蛋白在牙槽骨缺损种植引导骨再生后骨量的变化。方法：选择106例单颗前牙缺失伴唇侧骨缺损患者,进行种植体种植同期引导骨再生。按随机数字表法随机分为2组,实验组（53例）采用Bio-Oss骨粉联合富血小板纤维蛋白+生物膜引导骨再生,对照组（53例）采用Bio-Oss骨粉联合生物膜引导骨再生。评价2组种植成功率、术后并发症率、种植体唇侧骨壁厚度、骨缺损再生情况。采用SPSS 25.0软件包对数据进行统计学分析。结果：2组种植体种植成功率差异无统计学意义（96.23%:88.68%,P>0.05）。种植后12个月,实验组种植体唇侧骨壁厚度显著大于对照组[（2.72±0.43） mm:（2.51±0.36） mm,P<0.05],不同位点种植体唇侧骨壁厚度大于对照组（P<0.05）,出血指数[（0.32±0.02）:（0.42±0.03）]、探诊深度[（3.31±0.69） mm:（4.32±0.95） mm]、附着丧失[（3.06±0.52） mm:（5.24±1.35） mm]均显著小于对照组（P<0.05）,植骨高度[（2.61±0.52） mm:（2.31±0.35） mm]、成骨高度[（2.59±0.32） mm:（2.01±0.16） mm] 显著大于对照组（P<0.05）。2组患者并发症发生率相比差异无统计学意义（1.89%:5.66%, P>0.05）。结论：Bio-Oss骨粉联合富血小板纤维蛋白可减少骨缺损种植引导骨再生后骨量丢失,促进骨缺损再生。     

Effect of diabetes and metabolic control on de novo bone formation following guided bone regeneration

Objectives: To evaluate histologically and morphometrically the effect of experimental diabetes and metabolic control on de novo bone formation following guided bone regeneration (GBR). Methods: Thirty‐five Wistar rats were allocated in three experimental groups: (a) uncontrolled, streptozotocin‐induced diabetes (D); (b) insulin‐controlled diabetes (CD); (c) healthy (H). A standardised titanium microimplant with sandblasted and acid‐etched surface was placed into the inferior border of the mandible bilaterally. On the test site, the microimplant was covered with a titanium reinforced expanded polytetrafluoroethylene membrane securely fixed in the mandible according to the GBR principle. The contralateral site served as control. Following 90 days of healing, undecalcified sections were prepared and planimetric measurements of the per cent vertical height of newly formed bone and the per cent new bone‐to‐implant contact were performed. Results: In all experimental groups, at the GBR treated sites, significant neo‐osteogenesis was observed. The vertical height of the newly formed bone and per cent bone‐to‐implant contact were not statistically significantly different among the H (51.3±7.2% and 50±6.8%), D (30.5±13.4% and 35±16.8%) and CD (41.6±8.3% and 39.9±6.5%) groups. However, uncontrolled diabetes was related to higher outcome variability and increased rate of infectious complications. In the control sites, marginal bone loss was observed in the D group, whereas, in the H and CD groups, minimal new bone formation was observed. Conclusions: Significant de novo bone formation can be achieved via GBR treatment even in the presence of uncontrolled diabetes, although less predictably compared with the healthy status. Insulin‐mediated metabolic control may reverse these adverse effects. To cite this article: Retzepi M, Lewis MP, Donos N. Effect of diabetes and metabolic control on de novo bone formation following guided bone regeneration.
Clin. Oral Impl. Res. 21 , 2009; 71–79.     

Role of chitin beads in the formation of jaw bone by guided tissue regeneration. An experiment in the rat

It has been reported that local application of bone grafts or synthetic bone substitutes (filler materials) may favour bone formation when used in combination with guided tissue regeneration (GTR). Therefore, the aim of the present investigation was to evaluate the effect of application of chitin beads (a bioabsorbable natural polymer) as a bone substitute in bone formation by GTR. The experiment was carried out in 25 rats. The mandibular ramus was exposed on one side after elevation of a muscle-periosteal flap, and a teflon capsule filled with chitin beads (2.0 mm in diameter) was placed with its opening facing the lateral aspect of the ramus. On the contralateral side of the jaw, serving as control, an empty teflon capsule was placed in the same manner. Groups of 5 animals were sacrificed at 7, 15, 30, 60 and 120 days following capsule placement. Histological analysis demonstrated that the amount of newly formed bone was similar in both experimental and control specimens, amounting to approximately 3% of the central/largest, cross-sectional area created by the capsule at 15 days, and to approximately 9% of this area at 30 days following capsule placement. At 60 and 120 days, however, the amount of newly formed bone observed in the control specimens was twice as large as that observed in the test specimens, amounting to approximately 31% of the cross-sectional area created by the capsule at 60 days, and to approximately 45% at 120 days. It is concluded that, although chitin beads (2.0 mm in diameter) are biocompatible, their presence retards bone formation in the model system used.     

釉质基质蛋白促进纯钛种植体表面骨形成的研究

目的　采用背反射电子(BSE)显微镜图像分析,定量研究釉质基质蛋白对纯钛种植体表面新骨形成的诱导作用。方法　实验用的纯钛种植体采用放电加工法特制而成,直径为1.6mm ,长度为3.5mm。种植体植入的部位为Wistar大鼠的两侧股骨,一侧作为实验组,种植窝内使用釉质基质蛋白Emdogain ;另一侧作为对照组,种植窝内仅使用釉质基质蛋白的载体丙二醇藻酸酯(PGA)。观察种植体植入后第14天和第30天种植体周围的新骨形成。结果　种植体植入后第14天,实验组和对照组种植体表面以及骨髓腔内均可见少量的新生小梁骨形成。种植体植入后的第30天,种植体周围新生小梁骨的量实验组高于对照组。结论　釉质基质蛋白可以促进种植体周围新骨的形成。     

降钙素基因相关肽在骨组织再生中的作用及机制

骨量不足是目前口腔种植修复中经常面临的问题,常用的骨组织再生办法有很多,如自体骨移植、生物骨粉及富血小板纤维膜的利用等,但临床效果都不是很显著.骨是一种由破骨和成骨细胞介导的处于动态代谢更新状态的组织,骨代谢受各种全身因素的影响,降钙素基冈相关肽(CGRP)是一种在人体广泛分布的神经肽,多项研究表明其在骨代谢中具有重要作用,特别是在成骨方面.其具体成骨作用及机制尚未完全清楚,一直在探讨之中,本文对此作一综述.     

Guided bone regeneration: materials and biological mechanisms revisited

Guided bone regeneration (GBR) is commonly used in combination with the installment of titanium implants. The application of a membrane to exclude non‐osteogenic tissues from interfering with bone regeneration is a key principle of GBR. Membrane materials possess a number of properties which are amenable to modification. A large number of membranes have been introduced for experimental and clinical verification. This prompts the need for an update on membrane properties and the biological outcomes, as well as a critical assessment of the biological mechanisms governing bone regeneration in defects covered by membranes. The relevant literature for this narrative review was assessed after a MEDLINE/PubMed database search. Experimental data suggest that different modifications of the physicochemical and mechanical properties of membranes may promote bone regeneration. Nevertheless, the precise role of membrane porosities for the barrier function of GBR membranes still awaits elucidation. Novel experimental findings also suggest an active role of the membrane compartment per se in promoting the regenerative processes in the underlying defect during GBR, instead of being purely a passive barrier. The optimization of membrane materials by systematically addressing both the barrier and the bioactive properties is an important strategy in this field of research.