Early therapeutic effect of platelet-rich fibrin combined with allogeneic bone marrow-derived stem cells on rats’ critical-sized mandibular defects

BACKGROUND Critically sized bone defects represent a significant challenge to orthopaedic surgeons worldwide.These defects generally result from severe trauma or resection of a whole large tumour.Autologous bone grafts are the current gold standard for the reconstruction of such defects.However,due to increased patient morbidity and the need for a second operative site,other lines of treatment should be introduced.To find alternative unconventional therapies to manage such defects,bone tissue engineering using a combination of suitable bioactive factors,cells,and biocompatible scaffolds offers a promising new approach for bone regeneration.AIM To evaluate the healing capacity of platelet-rich fibrin(PRF)membranes seeded with allogeneic mesenchymal bone marrow-derived stem cells(BMSCs)on critically sized mandibular defects in a rat model.METHODS Sixty-three Sprague Dawley rats were subjected to bilateral bone defects of critical size in the mandibles created by a 5-mm diameter trephine bur.Rats were allocated to three equal groups of 21 rats each.Group I bone defects were irrigated with normal saline and designed as negative controls.Defects of group II were grafted with PRF membranes and served as positive controls,while defects of group III were grafted with PRF membranes seeded with allogeneic BMSCs.Seven rats from each group were killed at 1,2 and 4 wk.The mandibles were dissected and prepared for routine haematoxylin and eosin(HE)staining,Masson's trichrome staining and CD68 immunohistochemical staining.RESULTS Four weeks postoperatively,the percentage area of newly formed bone was significantly higher in group III(0.88±0.02)than in groups I(0.02±0.00)and II(0.60±0.02).The amount of granulation tissue formation was lower in group III(0.12±0.02)than in groups I(0.20±0.02)and II(0.40±0.02).The number of inflammatory cells was lower in group III(0.29±0.03)than in groups I(4.82±0.08)and II(3.09±0.07).CONCLUSION Bone regenerative quality of critically sized mandibular bone defects in rats was better promoted by PRF membranes seeded with BMSCs than with PRF membranes alone.

Repair of oral mandibular defects with rib composite flap pedicled with internal thoracic

Objective To study feasibility and value of repair of oral mandibular defects with rib composite flap pedicled with internal thoracic vessels in basic level hospitals. Methods The clinical materials in 13 cases uith mandibular defects which were repaired with rib compos-

Healing Mechanism and Osteogenic Capacity of Bovine Bone Mineral—Human Amniotic Mesenchymal Stem Celland Autogenous Bone Graft in Critical Size Mandibular Defect

Experiments on maxillofacial bone tissue engineering showed the promising result;however, its healing mechanisms and effectiveness had not been fully understood. The aim of this study is to compare the bone healing mechanism and osteogenic capacity between bovine bone mineral loaded with hAMSC and autogenous bone graft in the reconstruction of critical size mandibular bone defect. Critical size defects were made at the mandible of 45 New Zealand white rabbits reconstructed with BBM-hAMSC, BBM alone, and ABG, respectively. At the end of first, second, and twelfth weeks, five rabbits from each experimental week were sacrificed for histology and immunohistochemistry staining. Expressions of vascular endothelial growth factor (VEGF), bone mor-phogenic proteins-2 (BMP2), Runx2 and the amount of angiogenesis were analyzed in the first and second week groups, while expressions of Runx2, osteocalcin, collagen type-I fibres, trabecular area and bone incorporation were analyzed in the twelfth week groups. The result showed that expressions of VEGF, BMP2 and Runx2 as well as the amount of angiogenesis were higher in ABG compared with BBM-hAMSC group in the first and second weeks of healing. The result of twelfth week of healing showed that expressions of Runx2 and osteocalcin as well as the thickness of collagen type-I fibres were significantly higher in BBM-hAMSC compared to ABG group, while there was no statistically difference in trabecular area and bone incorporation between BBM-hAMSC and ABG group. This study concluded that early healing activities were higher in auto-genous bone graft than in BBM-hAMSC, while osteogenic activities in the late stage of healing were higher in BBM-hAMSC compared to autogenous bone graft. It was also concluded that the osteo-genic capacity of BBM-hAMSC was comparable to autogenous bone graft in the reconstruction of critical size defect in the mandible.

Study on repairing canine mandibular defect with porous Mg-Sr alloy combined with Mg-Sr alloy membrane

To discuss the feasibility of the application of porous Mg-Sr alloy combined with Mg-Sr alloy membrane in the repair of mandibular defects in dogs.The second and third mandibular premolars on both sides were extracted from six dogs.The model of mandible buccal fenestration bone defects were prepared after the sockets healed.Twelve bone defects were randomly divided into groups A and B,then Mg-Sr alloy was implanted in bone defects of group A and covered by Mg-Sr alloy membrane while Mg-Sr alloy was implanted in bone defects of group B and covered by mineralized collagen membrane.Bone defects observed on cone beam computed tomographic images and comparing the gray value of the two groups after 4,8 and 12 weeks.After 12 weeks,the healing of bone defects were evaluated by gross observation,X-ray microscopes and histological observation of hard tissue.Bone defects in each group were repaired.At 8 and 12 weeks,the gray value of group A was higher than that of group B(P<0.05).At 12 weeks,the bone volume fraction of group A was higher than that of group B(P<0.05).The newly woven bone in group A is thick and arranged staggered,which was better than that of group B.Porous Mg-Sr alloy combined with Mg-Sr alloy membrane could further promote the repair of mandibular defects,and obtain good osteogenic effect.

Three-dimensional printed tissue engineered bone for canine mandibular defects

Background:Three-dimensional(3D)printed tissue engineered bone was used to repair the bone tissue defects in the oral and maxillofacial(OMF)region of experimental dogs.Material and methods:Canine bone marrow stromal cells(BMSCs)were obtained from 9 male Beagle dogs and in vitro cultured for osteogenic differentiation.The OMF region was scanned for 3D printed surgical guide plate and mold by ProJet1200 high-precision printer using implant materials followed sintering at 1250℃.The tissue engineered bones was co-cultured with BASCs for 2 or 8 d.The cell scaffold composite was placed in the defects and fixed in 9 dogs in 3 groups.Postoperative CT and/or micro-CT scans were performed to observe the osteogenesis and material degradation.Results:BMSCs were cultured with osteogenic differentiation in the second generation(P2).The nanoporous hydroxyapatite implant was made using the 3D printing mold with the white porous structure and the hard texture.BMSCs with osteogenic induction were densely covered with the surface of the material after co-culture and ECM was secreted to form calcium-like crystal nodules.The effect of the tissue engineered bone on the in vivo osteogenesis ability was no significant difference between 2 d and 8 d of the compositing time.Conclusions:The tissue-engineered bone was constructed by 3D printing mold and hightemperature sintering to produce nanoporous hydroxyapatite scaffolds,which repair in situ bone defects in experimental dogs.The time of compositing for tissue engineered bone was reduced from 8 d to 2 d without the in vivo effect.

A novel conceptual design of a biomimetic oral implant and its biomechanical effect on the repairment of a large mandibular defect

This study aimed to propose a novel biomimetic design strategy of an oral implant and to numerically examine its biomechanical effect according to clinical interests.The designed implant conceptually mimicked the morphology and elastic modulus of the mandibular bone.Basing on a CT-image-based patient-specific reconstruction of the tumor-excised mandible,the biomechanical effects of the implants with three materials(PEEK/n-HA/CF,PEEK/HA and Ti6Al4V),two surgical conditions(removed and retained muscles),and two postoperative stages(early and late)were fully investigated by a static finite element analysis.Moreover,according to clinical interests(e.g.failure and stability of the implant and rivets),maximum von Mises stresses and strains of the implant and rivets,maximum implant-bone gap in the early postoperative stage,and maximum von Mises stress of the mandible were mainly analyzed.The results showed that the implant composed of Ti6Al4V material was suitable for the current design strategy with respect to the other two PEEK-based materials.Although the implants in the muscle-retained surgical condition had relative greater indices compared to the muscle-removed surgical condition,the index difference between the two conditions was slight.The biomechanical indices indicating the failure and loosening risks of implant and rivets were much reduced in the late postoperative stage with respect to the early postoperative stage due to the osteointegration at the implant-bone interface.Generally,the proposed novel design strategy could be useful to guide the design of the oral implant addressing different implant materials and surgical conditions,and further made proper suggestion to clinicians and patients.

Digital design of scaffold for mandibular defect repair based on tissue engineering

Mandibular defect occurs more frequently in recent years,and clinical repair operations via bone transplantation are difficult to be further improved due to some intrinsic flaws.Tissue engineering,which is a hot research field of biomedical engineering,provides a new direction for mandibular defect repair.As the basis and key part of tissue engineering,scaffolds have been widely and deeply studied in regards to the basic theory,as well as the principle of biomaterial,structure,design,and fabrication method.However,little research is targeted at tissue regeneration for clinic repair operations.Since mandibular bone has a special structure,rather than uniform and regular structure in existing studies,a methodology based on tissue engineering is proposed for mandibular defect repair in this paper.Key steps regarding scaffold digital design,such as external shape design and internal microstructure design directly based on triangular meshes are discussed in detail.By analyzing the theoretical model and the measured data from the test parts fabricated by rapid prototyping,the feasibility and effectiveness of the proposed methodology are properly verified.More works about mechanical and biological improvements need to be done to promote its clinical application in future.

重度牙周破坏对下颌第一磨牙拔牙后种植手术方式影响的回顾性研究

目的:对下颌第一磨牙拔除后行种植修复的病例进行回顾性研究,探索重度牙周破坏(advanced periodontal defect,APD)对拔牙后种植手术方式的影响。方法:纳入下颌第一磨牙拔除后自然愈合3~12个月行种植手术的患者176例,共179个种植位点,进行回顾性分析,记录患者年龄、性别、缺牙时间以及拔牙时是否有APD。采用多因素Logistic回归,分析拔牙前APD是否是种植时行引导性骨再生(guided bone regeneration,GBR)的风险因素。结果:对年龄、性别、缺牙时间等因素校正后,结果显示,有APD的下颌第一磨牙,种植时行GBR的风险是无APD位点的4.738倍(95%可信区间:1.650~13.609,P<0.05)。结论:APD的下颌第一磨牙拔除后,种植手术时行GBR的可能性更大。

下颌骨缺损患者对咬合功能锻炼需求的质性研究

目的:了解口腔肿瘤术后下颌骨缺损患者咬合功能锻炼的现状与需求。方法 :采用目的 抽样法,对27例口腔肿瘤术后下颌骨缺损患者进行半结构式访谈,借鉴扎根理论的三级编码体系,运用Nvivo11质性分析软件进行自下而上的编码分析。结果:下颌骨缺损患者咬合功能锻炼的现状与需求可归纳为5个主题,即下颌骨缺损对患者的影响、咬合功能锻炼相关知识缺乏、对咬合功能锻炼内容的需求(期待专业化健康指导)、对咬合功能锻炼宣教方式的需求(期待多元化宣教方式及各种阻碍因素导致患者依从性降低)。结论 :建立统一规范的咬合功能锻炼方案,临床医护人员应关注患者的各种阻碍因素,调节患者心理状态,最大限度提高患者咬合功能锻炼的依从性。

下颌骨缺损腓骨肌皮瓣重建后种植义齿修复的临床效果评价

目的:评价下颌骨缺损腓骨肌皮瓣重建后种植义齿修复的临床疗效。方法:纳入15例因肿瘤行下颌骨缺损腓骨肌皮瓣重建后的患者,评价在种植义齿修复后2年种植体的存留率、种植体周探诊深度(PD)、改良龈沟出血指(mSBI)、种植体边缘骨高度(MBL)。结果:62枚种植体在行使功能后2年种植体存留率100%;种植修复2年后,与修复前相比,MBL、PD及mSBI未见统计学差异(P>0.05);PD>4 mm时,mSBI显著增加(P<0.05)。结论:下颌骨缺损腓骨肌皮瓣重建后种植义齿修复取得了良好的临床疗效,PD≤4 mm的种植体表现出更好的稳定性。

基于Micro-CT评价超声骨焊接技术PDLLA材料对骨愈合性能的影响

目的采用微焦点断层扫描(Micro-CT)评价超声骨焊接技术应用过程中超声震荡产热作用下PDLLA材料对骨愈合性能的影响。方法选择SPF级雄性新西兰大白兔36只,随机分为超声骨焊接技术辅助PDLLA材料组(A组)、拧入技术辅助PDLLA材料组(B组)、假手术组(C组)、空白对照组(D组),各9只。于术后4、8、12周取下颌骨标本,周围骨组织进行HE染色,观察各组植入钉周围情况。对术后4、8、12周的下颌骨大体标本拍摄Micro-CT图,使用VG Studio MAX软件进行三维重建,摆正数据样本,即颌骨颊侧造模处为轴向,动态分析植入钉体积、植入钉周围200μm环状区及骨缺损处的植入材料体积数、相对骨体积分数(BV/TV)、骨小梁厚度(Tb.Th)、骨小梁数(Tb.N)、骨小梁间隙(Tb.Sp)等骨愈合相关指标。结果HE染色结果显示,按3个时间可动态观察到A、B、C组骨缺损处骨性骨痂替代纤维性骨痂,形成类骨质,编织骨的过程符合正常骨损伤愈合的过程。Micro-CT结果显示,A、B组术后3个时间点的材料体积比较差异均无统计学意义(P>0.05);在3个时间点,4组植入钉周围200μm环状区中BV/TV、Tb.Th、Tb.N、Tb.Sp比较差异均无统计学意义(P>0.05);在骨缺损处,A、B、C组三个时间点BV/TV、Tb.Th、Tb.N、Tb.Sp比较差异无统计学意义(P>0.05);术后4周,与D组比较,A、B、C组BV/TV、Tb.Th、Tb.N、Tb.Sp差异有统计学意义(P<0.05);与C组比较,A、B组Tb.N差异有统计学意义(P<0.01)。术后8周,与D组比较,A、B、C组BV/TV、Tb.Th、Tb.N、Tb.Sp差异有统计学意义(P<0.05);术后12周,与D组比较,A、B、C组BV/TV、Tb.Th、Tb.Sp差异有统计学意义(P<0.05)。结论超声骨焊接技术其超声震荡产热作用下PDLLA材料对骨愈合性能无不良影响。

同期神经化腓骨瓣用于下颌骨重建及下唇感觉恢复的术式初探

目的:探讨下颌骨及下牙槽神经因肿瘤截除后,同期颌骨重建及感觉恢复的新方法,为临床提供参考。方法:对1例下颌骨成釉细胞瘤患者行下颌骨节段性切除,术中一并切除与病灶密切的下牙槽神经,同期行神经化血管化腓骨游离皮瓣移植修复。术后通过影像学观察其移植骨吸收情况,应用两点辨别觉和感觉测试丝评估感觉保存效果。结果:术后随访9个月,患者颜面自然对称,皮瓣存活良好,移植骨稳定未见明显吸收,下唇感觉功能良好,颏部稍次,无咬唇、流涎等问题;受区及供区未见并发症。结论:同期重建神经的新方法对腓骨瓣移植重建下颌骨时恢复下唇感觉及预防移植骨术后吸收具有较好效果。

The sequential treatment of extensive mandibular ameloblastoma

Ameloblastoma is the most frequent odontogenic tumor of the jaw. If not treated, ameloblastoma can gain an enormous size and cause severe facial disfigurement and functional impairment. Here we report two patients afflicted with extensive mandibular ameloblastoma (sized in 23 cm × 18 cm × 17 cm and 15 cm × 12 cm × 10 cm, respectively). Both the patients received the same sequential treatment including radical tumor resection, simultaneous reconstruction with fibula free flap graft, vertical distraction osteogenesis on the fibula graft, placement of endosseous dental implants, and final pros-thodontic rehabilitation. It took about 15 months to finish the entire course of treatment. And after the four-year follow-up, neither soft tissue related, nor hard tissue related problems were observed. Satisfactory facial symmetry, chewing and speech functions of the patients were restored. So this sequential treatment for extensive mandibular ameloblastoma can obtain an excellent effect by the shortest time and the lowest economical cost. Furthermore, the series also can be used to reconstruct giant mandibular defects caused by different reasons.

重组人源肿瘤坏死因子受体融合蛋白对大鼠下颌骨缺损的干预效果

目的:通过大鼠下颌骨缺损再植的实验动物模型,基于Janus激酶-信号转导与转录激活因子(Janus kinase-signal transducers and activators of transcription,JAK-STAT)通路探讨注射重组人源肿瘤坏死因子受体融合蛋白(recombinant human tumor necrosis factor receptor:Fc fusion protein,rhTNFR:Fc)对下颌骨缺损大鼠的干预效果。方法:将70只(雌雄各半)7~8周龄的健康SD大鼠随机分为3组,分别为空白组(10只)、对照组(30只)和实验组(30只)。实验组:于大鼠骨缺损处注入含有Rh TNFR:Fc(45 mg/kg)的Bio-Oss骨颗粒,其上覆盖Bio-Gide胶原膜;对照组:于大鼠缺损处注入含25μL 0.9%氯化钠溶液的Bio-Oss骨颗粒,同样覆盖Bio-Gide胶原膜;空白对照组为健康大鼠。取所有大鼠下颌骨组织,观察其形态学变化,行组织形态计量学测定。实验组和对照组大鼠于术后3、6、9周时被分批处死,取其左侧下颌骨进行炎症因子白细胞介素-6(interleukin-6,IL-6)和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)表达水平的检测,同时检测组织中凋亡相关分子Bax、Bcl-2、p-JAK2和p-STAT3蛋白的表达。结果:与对照组比较,实验组的缺损面积显著减少,IL-6和TNF-α的浓度显著下降,而凋亡相关分子Bax、p-JAK2和p-STAT3的表达显著下降,Bcl-2表达显著升高(P<0.05);与空白组比较,对照组和实验组缺损面积显著增加,缺损模型建立成功。结论:局部注射rh TNFR:Fc与Bio-Oss骨颗粒能够有效地促进下颌骨缺损修复,并且效果显著优于只使用Bio-Oss骨颗粒的组别,其修复作用与抑制细胞凋亡的能力相关,通过实验我们发现JAK2-STAT3细胞信号通路在其中发挥了重要作用。

同期神经化血管化髂骨瓣修复下颌骨及神经缺损

颌骨大型缺损的功能性重建是口腔颌面外科临床的重点问题,自体骨移植是主要的方法。然而,自体骨移植后的骨质易吸收,即使通过吻合血管,移植骨的自发性疏松化仍然严重影响牙种植及功能恢复。因此,血管化自体骨移植的疏松化成为颌骨重建的重要并发症之一,尚无预防措施。血供充足的自体骨无法避免自身疏松化的问题提示:血供之外被长期忽略的神经等系统因素可能调控移植骨内环境。笔者基于前期神经微环境调控间充质干细胞的系列研究,通过构建神经化血管化髂骨瓣动物模型及尸体解剖,提出了同期神经支配的血管化髂骨瓣修复下颌骨缺损的新术式。神经化血管化髂骨瓣移植是在髂骨瓣(骨肌皮瓣)植入受区并行血管吻合后,对同时获取的支配髂骨的髂腹股沟神经(传统方法一般忽略并牺牲)与下牙槽神经近心端及颏神经行显微缝合。笔者团队通过开展临床回顾性研究和前瞻性随机对照试验,证实同期神经化血管化髂骨瓣移植的新方法不仅抵御骨质吸收,而且能够恢复唇等周围软组织的感觉,可解决颌骨重建后感觉缺失及疏松化的关键问题,保证了牙种植义齿的成功,并提出“血供+神经”双系统骨移植的新理念。

三维打印+膜诱导技术修复重建下颌骨节段性缺损1例报道

目的:报道1例2021年2月就诊于我院的下颌骨右侧成釉细胞瘤,采用Masquelet膜诱导技术(Masquelet's induced membrane technique,MIMT)重建患者下颌骨节段性缺损。方法:依据MIMT原则,给予患者Ⅰ期下颌骨部分切除+骨水泥植入,Ⅱ期依托数字化技术三维打印模型预塑钛网,移植髂骨碎骨块,Ⅲ期拆除重建板及钛网。结果:根据影像学检查及术中所见,应用MIMT修复重建下颌骨节段性缺损效果良好。结论:三维打印与MIMT应用于下颌骨节段性缺损能取得良好的成骨效果,可进一步进行研究。

不同类型血管化游离腓骨瓣修复下颌骨缺损的回顾性分析

目的:探讨利用血管化游离腓骨瓣(free fibular flap, FFF)重建面下1/3软硬组织缺损的方法,评价利用腓骨瓣修复下颌骨缺损的多样性及灵活性。方法:收集因良、恶性肿瘤行下颌骨节段性切除同期行腓骨瓣修复的患者35例,统计患者下颌骨缺损类型、术前设计、腓骨瓣修复方法及携带皮岛的情况。结果:根据COM分类法进行分类,Ⅰ类6例、Ⅱ类26例、Ⅲ类3例,缺损长度为4.85~17.00 cm,平均(8.29±2.69)cm。单层腓骨瓣修复28例,其中1例单层腓骨宽达2.16 cm;折叠腓骨瓣修复6例;单层腓骨瓣+游离植骨1例,共8例患者下颌骨高度得到完美恢复。皮岛方面,因穿支缺如无皮岛者1例,30例携带1个皮岛,4例携带双皮岛,软组织缺损修复效果良好。结论:血管化FFF应用灵活,除能恢复下颌骨连续性外,还可以通过多种手段恢复下颌骨高度,并携带双皮岛修复复杂的软组织缺损。

应用龈壁提升术修复下颌第二磨牙远中龈下缺损的临床效果

目的 比较龈壁提升和冠延长术后,CAD/CAM玻璃陶瓷全冠对下颌第二磨牙根管治疗后远中龈下缺损的修复效果。方法 选择103颗患牙,随机分为实验组和对照组,分别进行龈壁提升术和牙冠延长术,然后用CAD/CAM玻璃陶瓷全冠修复。修复完成后6个月、12个月、24个月和36个月复查,按照改良美国公共健康协会修订标准(USPHS),对两组修复体进行评估和比较。结果 各复查时间所有修复体达到A级的比例80.0%以上,边缘密合度均无C级和D级评价,修复体外形、边缘着色情况、颜色匹配度、继发龋和修复体表面质地等无C级评价。修复后各时间段各指标比较差异均不显著(P>0.05)。结论 龈壁提升和冠延长术修复下颌第二磨牙远中龈下缺损的中短期临床效果相近。

节段性下颌骨切除腓骨重建后全口义齿修复1例

下颌骨缺损血管化游离骨移植后,因重建的骨高度不足,附着龈、前庭沟、舌颌沟缺失,使义齿修复极具挑战性。本文报道了1例因药物相关性颌骨坏死行节段性下颌骨切除血管化游离腓骨重建,术后采取调整后的全口义齿修复方案恢复咀嚼、发音、美观功能的治疗案例。

腓骨复合瓣游离移植修复下颌骨缺损

目的 总结应用游离腓骨复合瓣修复下颌骨缺损的经验。方法 1999年 6月～ 2 0 0 0年 11月对5 8例应用腓骨复合瓣游离移植修复下颌骨缺损的病例作回顾性研究 ,其中男 37例 ,女 2 1例。年龄 12～ 6 5岁 ,平均4 0 .9岁。分析下颌骨缺损原因 ,分析腓骨瓣设计、受区血管、组织瓣成活情况及术后并发症的发生情况。结果 5 8例中 5 2例为肿瘤切除术后修复 ,其中 4 3例为一期修复 ,9例为二期修复。采用游离腓骨复合骨瓣的腓骨长度 4～2 1cm ,平均 11.4 cm ;腓骨的截骨为 1～ 4次数 ,平均 2 .1次 ;骨瓣带皮岛最大范围 12 cm× 8cm,最小 3.0 cm×1.5 cm。术后游离腓骨瓣的临床成功率为 96 .6 % (5 6 /5 8) ,失败 2例。受供区并发症主要为血肿、积液、创口感染和腺瘘 ,有 4例为植皮坏死和创口感染 ,发生率为 2 4 .1% ,但不影响效果。结论 游离腓骨瓣在修复下颌骨缺损中具有操作灵活 ,安全可靠 ,制备简便 ,并发症少 。