微骨折技术与骨软骨移植治疗关节软骨缺损

背景：关节镜下微骨折治疗与骨软骨移植是关节软骨缺损主要的治疗方法之一,具有广阔的应用前景。 目的：探讨关节镜下微骨折治疗与自体和同种异体骨软骨移植治疗膝骨关节炎合并关节软骨缺损的效果。 方法：应用关节镜下微骨折治疗清理术结合软骨缺损区微骨折术治疗膝骨关节炎的临床疗效、临床症状及Tegner运动评级判定疗效并随访观察3-24个月。自体骨软骨移植治疗关节软骨缺损的患者进行观察随访,通过评价移植后关节活动度、临床症状的改善、关节影像学检查等评估自体骨软骨移植治疗的效果。并对同种异体骨软骨移植治疗关节软骨缺损进行动物实验研究,通过对移植部位的大体观察、组织学观察以及免疫组织化学染色观察,评估同种异体骨软骨移植治疗的效果。 结果与结论：关节软骨缺损应用关节镜下微骨折治疗后的患者,关节清理术结合软骨缺损区微骨折术总有效率89.7%。关节软骨缺损应用自体骨软骨移植治疗后的患者,关节疼痛、肿胀的症状改善,关节活动度正常,偶有关节静息痛或活动后轻微疼痛,影像学检查见移植骨软骨位置良好,修复愈合良好。关节软骨缺损应用同种异体骨软骨移植治疗后的实验动物,关节活动度正常,移植关节面光整,关节软骨被透明软骨覆盖,细胞有序排列,软骨基质分泌,修复软骨Ⅱ型胶原免疫组织化学染色强阳性。     

软骨下骨量变化与软骨退变的相关性

背景：关节软骨与软骨下骨在骨关节炎病变进程中的相互作用机制目前尚未完全阐明。软骨下骨量改变在骨关节炎病理进程中亦发挥重要作用。 目的：分析2种手术方式及2种蛋白酶诱导建立兔膝关节骨关节炎动物模型的效果,以及软骨下骨量变化与关节软骨退变的相关性。 方法：32只新西兰大白兔随机分为4组：Hulth模型组、前交叉韧带切断模型组、Ⅱ型胶原蛋白酶组及木瓜蛋白酶组,每组8只,右膝关节造模,左膝关节作为自身对照。造模后0,4,8周行DXA扫描,8周行MRI扫描后处死实验动物,取双侧膝关节制作病理组织学切片,比较各组膝关节影像学表现、大体形态及病理变化,并采用Mankin评分进行定量分析。 结果与结论：造模后0,4,8周实验侧膝关节骨密度进行性降低,骨量降低程度Hulth模型组>前交叉韧带切断模型组>Ⅱ型胶原蛋白酶组>木瓜蛋白酶组。MRI显示实验侧股骨内外髁关节软骨厚度变薄,厚度Hulth模型组<前交叉韧带切断模型组<Ⅱ型胶原蛋白酶组<木瓜蛋白酶组。大体标本、组织切片观察及Mankin评分显示手术建模组骨关节炎程度较药物组重,Hulth模型组病变最重,木瓜蛋白酶组最轻。结果说明关节内手术及关节腔内注射蛋白酶均能建立骨关节炎动物模型;手术造模可复制出中晚期骨关节炎,药物诱导可产生骨关节炎早期改变。骨关节炎病变严重程度与软骨下骨骨密度呈负相关;关节软骨退变和软骨下骨改变相互关联,病变进行性发展。     

异体和自体全厚关节软骨移植的实验研究

异体和自体新鲜全厚关节软骨移植共３２只新西兰兔。异体移植有排斥反应，关节软骨完全吸收，缺损区被宿主新生软骨修复。自体移植的软骨完全有活力，植骨裂隙由新生软骨修复。关节软骨无再生能力，修复软骨来自骨髓松质骨的间充质细胞，术后控制性关节运动能促使软骨生长。新形成的软骨基质不及正常软骨基质质量好，甚至正常软骨与修复软骨间存在裂隙，不能完全融合。     

关节软骨的修复与修复失败

文题释义： 自体软骨细胞移植：对于3.5-10 cm2的软骨缺损或多个缺损来说,自体软骨细胞移植是一种有效的软骨修复措施,取少量患者自体软骨于体外培养软骨细胞,并增殖到一定数量后植入软骨缺损处,从而达到修复缺损的目的。 基质诱导的自体软骨细胞移植：把经培养增殖后的软骨细胞接种到Ⅰ/Ⅲ型双层胶原膜上,继续培养数日,细胞与支架结合紧密之后,使用生物蛋白胶粘贴到关节软骨缺损病灶底部。术后,软骨细胞从胶原膜上游离并穿过生物胶,迁徙到软骨缺损的基底部。胶原膜和生物胶逐步降解并被吸收。接种的软骨细胞在局部生长、繁殖,并分泌基质,形成新的软骨组织修复缺损。背景：由于关节软骨具有复杂的生物学特性和高度的耐用性,自然退变或创伤引起的缺损都可能导致其结构和功能上不可逆的损害,因此关节软骨损伤后的修复治疗是临床上急需解决的问题。 目的：报告关节软骨修复技术失败最常见的危险因素及其发生率,分析影响选择特定手术治疗方法来处理软骨修复失败最重要的因素。 方法：以“articular cartilage, repair, clinic/clinical failure, surgery”为检索词,检索 PubMed和MEDLINE数据库,时限为2007至2019年,语言限制为英文。初检得到文献约343篇,根据纳入排出标准筛选,共纳入38篇文章进行分析。 结果与结论：①微骨折术和软骨镶嵌成形术在关节软骨修复后的前期和中期显示出不可忽视的失败率,而使用自体软骨细胞移植和异体骨软骨移植修复关节软骨的效果更好。②对于软骨修复失败的治疗：在以往软骨修复失败的患者中应用异体骨软骨移植可能是一个安全的选择,但对于失败的异体骨软骨移植的修复则有更高的失败率;而既往自体软骨细胞移植或基质诱导的自体软骨细胞移植失败的患者,经进一步的自体软骨细胞移植或基质诱导的自体软骨细胞移植治疗后,其治疗效果是可以接受的。此外,有软骨下骨髓刺激病史的患者,自体软骨细胞移植的失败率更高。③软骨修复失败的处理取决于手术治疗失败的类型以及软骨缺损的面积、部位的不同,异体骨软骨移植是治疗软骨下骨髓刺激患者软骨修复失败的最可靠的方法,而自体软骨细胞移植或基质诱导的自体软骨细胞移植在既往软骨修复失败的患者中显示出可以接受的治疗效果,在处理软骨修复失败的患者时,应该特别注意软骨下骨质的情况。ORCID: 0000-0002-3907-9145(张宇) 中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程     

膝关节软骨损伤的治疗进展

[摘要]膝关节具有多样且复杂的运动形式,是人体承重最大的关节,最易导致关节软骨损伤。由于其再生修复的能力很弱,故其损伤后很难自身修复,进而导致骨关节炎的发生。膝关节软骨损伤后目前主要有以下的手术治疗方式：①自体骨软骨移植技术（马赛克移植技术）;②同种异体骨软骨移植技术;③自体软骨细胞移植; ④合成或生物支架植入（组织工程技术）;⑤微骨折技术;⑥粉碎软骨修复技术;⑦生物制剂辅助治疗。通过选择性运用上述治疗可以在短期内改善临床症状,延迟或者避免行关节置换手术,本文将对其一一进行综述。     

组织工程化软骨修复界面整合的体外模型

背景:随着组织工程学的发展,自体软骨细胞移植技术经常被用来修复软骨缺损,整合不良是导致修复失败的原因之一。许多体外模型被用来进行这方面的研究。目的:建立一种组织工程化软骨修复界面整合的体外实验模型并评价其效果。方法:制备猪体外软骨整合模型,获得21个软骨环,18只琼脂糖凝胶覆盖的软骨环设为琼脂糖凝胶组,剩余3个做无琼脂糖对照组,分别植入分离的软骨细胞,观察近期软骨环边界细胞漏出情况,分别在1,2,4周做切片、染色并行组织学观察,测量新生软骨平均面积并进行比较。结果与结论:无琼脂糖对照组由于软骨细胞早期从软骨环底部漏出,未能在软骨环中形成软骨细胞聚集,所以未做后期处理,而琼脂糖凝胶组则未发生。琼脂糖凝胶组1,2,4周做切片并行固定后组织切片分别用苏木精-伊红染色、阿利新蓝、番红O、Ⅱ型胶原免疫组化染色,移植的软骨细胞在软骨环内不断增殖,并且产生细胞外基质。在第1,2周的孵育中,新生软骨的面积明显增大,到第4周时,面积也有进一步增加,但是第2-4周的面积增加,差异无显著性意义(P0.05)。模型成功模拟了自体软骨细胞移植修复关节软骨缺损的体外整合过程,未来可应用于软骨整合及软骨组织工程的机制研究。     

组织工程方法修复类风湿性关节炎软骨缺损的研究进展

类风湿性关节炎作为一种自身免疫疾病,会造成关节腔内关节软骨损伤.由于关节腔内没有血管和淋巴组织,营养物质主要通过弥散方式抵达,导致受损伤的关节软骨自身修复能力有限,这是治疗关节炎的瓶颈所在.目前临床上修复关节软骨的措施主要有微骨折术、自体骨软骨移植、异体骨软骨移植等,但都存在一定不足.当前关节软骨缺损修复的研究热点是利用组织工程方法获得稳定的自体软骨细胞,并与相应的支架结合后移植到病变关节处,其优点是创伤小、副作用少且方便使用,可能成为未来治疗类风湿性关节炎软骨缺损的发展方向.本文针对该方法的具体步骤进行简述,包括动物模型、种子细胞、支架材料、复合体的构建及体内移植后的修复情况.     

IGF-1在股骨头再造关节软骨化生中的作用

目的观察分析大转子骨瓣表面骨膜及腱膜等纤维结缔组织向关节软骨转化的规律及胰岛素样生长因子-1(IGF-1)在软骨化生过程中的作用。方法制备液氮冷冻双侧股骨头缺血性坏死(Osteonecrosis of femoral head,ONFH)的动物模型。左侧股骨头造模后即缝合关节囊,右侧股骨头根据分组不同采用不同的处理方式:A组(骨瓣治疗组):带血管蒂大转子骨瓣进行股骨头再造;B组(骨瓣加Ad-IGF-1基因治疗治疗组):带血管蒂大转子骨瓣股骨头再造,关节内注入表达IGF-1的腺病毒载体(Ad-IGF-1);两组动物分别于3,6,12,18,24周每批4只处死,对骨瓣进行大体观察,组织病理学观察,免疫组化检测。结果所有动物左侧冷冻区组织坏死,纤维状物覆盖,碎片样组织修复。组织病理切片及免疫组化证实A组右侧骨瓣区自6周出现透明软骨细胞,B组右侧骨瓣区自3周出现透明软骨细胞,B组较A组修复效果好。结果经统计学处理有统计学意义。结论大转子表面的骨膜及腱膜能够向关节软骨化生,IGF-1对大转子表面的骨膜及腱膜向关节软骨化生有促进作用,为ONFH的外科治疗及生长因子的应用提供基础。     

健膝强骨丸对膝骨关节炎家兔模型关节软骨病理改变的影响

背景：膝骨关节炎的病理学改变不可逆转,属中医“痹证”范畴,治疗目的是缓解或解除症状,延缓关节退变。健膝强骨丸方是武汉大学基础医学院荆州市第三人民医院的经验方,可补益肝肾,祛风散寒,除湿通络,强骨健膝。 目的：观察健膝强骨丸对膝骨关节炎兔模型膝骨关节软骨的保护作用,及其对软骨细胞骨形态发生蛋白7表达的影响。 方法：36只新西兰兔随机分为3组,每组12只,分别运用改良Hulth术制备兔膝骨关节炎模型。造模后第6周,给药组予健膝强骨丸0.1 g/kg灌胃,模型组和正常对照组予等量生理盐水灌胃。给药4周后通过软骨Mankin’s评分方法行兔膝关节软骨评分,电镜下观察软骨形态,免疫组化法检测膝关节软骨细胞骨形态发生蛋白7表达情况。 结果与结论：给药组兔膝关节软骨病理退变程度较其他2组轻,膝关节软骨细胞骨形态发生蛋白7的表达量较其他2组高,差异有显著性意义(P < 0.05)。提示健膝强骨丸可增强膝骨关节炎模型兔关节软骨细胞骨形态发生蛋白7的表达,从而促进膝关节软骨再生,减少软骨变形坏死,达到治疗关节炎的目的。 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程全文链接：     

多孔钽支架与磷酸三钙复合骨膜移植修复软骨缺损的比较

背景：早期实验证实骨膜含有潜在形成软骨或骨的间充质干细胞,在适当的条件下可向软骨细胞分化。 目的：比较观察多孔钽支架复合骨膜移植与磷酸三钙复合骨膜移植修复软骨缺损的效果。 方法：取雌性兔24只随机分为2组。建立膝关节软骨缺损模型,分别填入多孔钽支架和磷酸三钙支架,表面覆盖预处理的反置骨膜。石膏固定2周。于12周麻醉后处死兔,观察滑膜、关节液、股骨髁软骨大体观及股骨髁软骨病理表现。采用改良的Mankin骨关节炎的评分法。 结果与结论：多孔钽组滑膜增生明显,新生软骨表层呈蓝白色,周缘欠光滑,甲苯胺蓝染色可见软骨细胞排列稍紊乱,软骨细胞数目正常,多孔钽内骨长入良好,Mankin评分为7.35分。磷酸三钙组新生软骨表层呈蓝白色,周缘欠光滑,甲苯胺蓝染色可见软骨细胞排列稍紊乱,软骨细胞数目正常,磷酸三钙内骨长入可,Mankin评分为7.43分(P > 0.05)。表明多孔钽支架复合骨膜移植与磷酸三钙复合骨膜移植修复方式对软骨修复的结果无明显差别,但多孔钽支架与周围骨组织融合优于磷酸三钙。     

Effects on articular cartilage of subchondral replacement with polymethylmethacrylate and calcium phosphate cement.

Bone defects were created in rabbit medial femoral condyle in a model where subchondral bone was completely removed or about 2 mm of subchondral bone was maintained. Groups without augmentation and augmented with autogenous bone, polymethylmethacrylate, or calcium phosphate cement were sacrificed at 3, 12, and 24 weeks for evaluation of articular cartilage and observation of bone formation. In the model in which subchondral bone was completely removed, collapse of the subchondral bone together with exfoliation and prolapse of cartilage developed early in all cases. In the model in which 2 mm of subchondral bone was maintained, degeneration of articular cartilage developed at 12 weeks in the group augmented with polymethylmethacrylate, showing a significant difference when compared to the contralateral untreated control group. The group augmented with calcium phosphate cement did not demonstrate any evident difference from the control group. Mechanical properties after subchondral replacement did not differ between the groups augmented with polymethylmethacrylate and calcium phosphate cement, although calcium phosphate cement was considered histologically superior. Calcium phosphate cement was a reliable subchondral replacement material when the bone defect is adjacent to the articular cartilage.     

Microdrilled cartilage defects treated with thrombin-solidified chitosan/blood implant regenerate a more hyaline, stable, and structurally integrated osteochondral unit compared to drilled controls

This study analyzed the long-term cartilage and subchondral bone repair of microdrilled defects treated with chitosan glycerol-phosphate/blood implant, using thrombin (Factor IIa) to accelerate in situ solidification. We also evaluated the cartilage repair response to six smaller microdrill holes compared with two larger holes. Bilateral knee trochlear cartilage defects were created in n=8 skeletally mature rabbits, drilled with six proximal 0.5 mm and two distal 0.9 mm holes, then covered with in situ-solidified IIa-implants (treated) or with IIa-alone (control). After 6.5 months of repair, cartilage repair tissues were analyzed by histological scoring and histomorphometry for hyaline matrix characteristics and osseous integration. Subchondral repair bone was analyzed by 3D microcomputed tomography and compared to acute defects (n=6) and intact trochlea (n=8). Implant-treated cartilage repair tissues had higher structural integrity through the entire defect (p=0.02), twofold higher percent staining for glycosaminoglycan (p=0.0004), and ~24% more collagen type II staining over the smaller drill holes (p=0.008) compared with controls. Otherwise, hole diameter had no specific effect on cartilage repair. The subchondral bone plate was partially restored in treated and control defects but less dense than intact trochlea, with evidence of incomplete regeneration of the calcified cartilage layer. More residual drill holes (p=0.054) were detected in control versus treated defects, and control defects with more than 40% residual holes presented abnormally thicker trabeculae compared with treated defects. Low osteoclast numbers after 6.5 months repair suggested that bone was no longer remodeling. The subchondral bone plate surrounding the defects exhibited a significant thickening compared with age-matched intact trochlea. These data suggest that debridement and drilling can lead to long-term subchondral bone changes outside the cartilage defect. Compared with drilled controls, chitosan implants solidified with thrombin elicited a more hyaline and structurally integrated osteochondral unit, features needed for long-term durability.     

脱钙骨基质与骨髓间充质干细胞共培养关节腔内的成软骨活性

背景：将骨髓间充质干细胞附着到支架材料上再植入关节软骨缺损处,细胞不但不消失,而且可形成新的软骨。 目的：观察同种异体脱钙骨基质与骨髓间充质干细胞共培养在关节内的成软骨活性。 方法：在54只青紫蓝兔单侧膝关节制作关节软骨全层缺损模型,随机分组：实验组在缺损处植入自体骨髓间充质干细胞与同种异体脱钙骨基质复合物,对照组缺损处仅植入同种异体脱钙骨基质,空白对照组未植入任何物质。 结果与结论：植入后12周,实验组缺损处修复组织呈软骨样,表面光滑平坦,与周围软骨整合的软骨细胞更为成熟,修复组织与软骨下骨结合牢固;修复组织的细胞为透明软骨样细胞,柱状排列,Ⅱ型胶原染色阳性,与周围软骨及软骨下骨整合良好,且实验组组织学评分优于对照组和空白对照组 (P < 0.01)。对照组缺损处修复组织呈纤维样,与周围软骨未结合,空白对照组缺损区无修复组织,两组均无Ⅱ型胶原染色阳性表达。表明同种异体脱钙骨基质与骨髓间充质干细胞共培养后植入膝关节可形成软骨样组织,有效修复关节软骨缺损。     

Parametric analysis of the stress distribution on the articular cartilage and subchondral bone

Few studies have stressed on the sensitivity of stress distribution in different mechanical properties of the articular cartilage and subchondral bone. The purpose of this study was to establish parametric variations of mechanical factors individually and examine how these biomechanical effects influenced the cartilage and subchondral bone plate stress fields in the hip joint. A finite element model including acetabulum and proximal femur was established to study the stress change associated with the thinning of cartilage, the increasing of subchondral bone modulus and the thickening of subchondral bone plate individually. The stress distributions in bone/cartilage interface were evaluated. Sensitivity of the stress magnitudes to the parametric changes was also analyzed. The results indicated that cartilage thinning has more significant effect than subchondral bone modulus increasing or thickening on the shear stress levels in subchondral bone/cartilage interface. Subchondral bone plate modulus increasing has mild effect on the shear stress in subchondral bone/cartilage interface. Cartilage thinning acts as a major influence on the development of the articular cartilage damage.     

多孔丝素蛋白/羟基磷灰石复合脂肪间充质干细胞修复兔关节软骨及软骨下骨缺损

背景：丝素蛋白/羟基磷灰石是细胞立体培养的良好支架,是临床常用的骨缺损修复材料,具有良好的生物相容性。脂肪干细胞具有向骨及软骨细胞分化的潜能,适合骨软骨缺损修复。 目的：观察转化生长因子β1和胰岛素样生长因子1联合成软骨诱导脂肪干细胞与丝素蛋白/羟基磷灰石复合后修复兔关节软骨及软骨下骨缺损的效果。 方法：取新西兰大白兔56只,2只用于传代培养脂肪间充质干细胞,以3×109 L-1浓度接种到丝素蛋白/羟基磷灰石。其余54只新西兰大白兔,在股骨髁间制备软骨缺损模型,随机分为细胞复合材料组、单纯材料组和空白对照组,细胞复合材料组植入复合脂肪间充质干细胞的丝素蛋白/羟基磷灰石;单纯材料组植入丝素蛋白/羟基磷灰石;空白对照组不作任何植入。从大体、影像学、组织学观察比较缺损的修复情况。 结果与结论：12周时大体观察、CT、磁共振和组织学检查细胞材料复合组软骨及软骨下骨缺损区完全被软骨组织修复,修复组织与周围软骨色泽相近,支架材料基本吸收,未见明显退变和白细胞浸润,所有标本均未见丝素蛋白残留。单纯材料组缺损区缩小、部分修复,且呈纤维软骨样修复。空白对照组缺损无明显修复。提示复合脂肪间充质干细胞的丝素蛋白/羟基磷灰石修复兔关节软骨及软骨下骨缺损能力优于单纯丝素蛋白/羟基磷灰石材料。丝素蛋白/羟基磷灰石复合脂肪间充质干细胞可形成透明软骨修复动物膝关节全层软骨缺损,重建关节的解剖结构和功能,可作为新型骨软骨组织工程支架。     

Mono-iodoacetate-induced histologic changes in subchondral bone and articular cartilage of rat femorotibial joints: an animal model of osteoarthritis

Osteoarthritis (OA) is a degenerative joint disease characterized by joint pain and a progressive loss of articular cartilage. Studies to elucidate the pathophysiology of OA have been hampered by the lack of a rapid, reproducible animal model that mimics both the histopathology and symptoms associated with the disease. Injection of mono-iodoacetate (MIA), an inhibitor of glycolysis, into the femorotibial joint of rodents promotes loss of articular cartilage similar to that noted in human OA. Here, we describe the histopathology in the subchondral bone and cartilage of rat (Wistar) knee joints treated with a single intra articular injection of MIA (1 mg) and sacrificed at 1, 3, 5, 7, 14, 28, and 56 days postinjection. Histologically, the early time points (days 1-7) were characterized by areas of chondrocyte degeneration/necrosis sometimes involving the entire thickness of the articular cartilage in the tibial plateaus and femoral condyles. Changes to the subchondral bone, as evidenced by increased numbers of osteoclasts and osteoblasts, were noted at by day 7. By 28 days, there was focal fragmentation and collapse of bony trabeculae with fibrosis and increased osteoclastic activity. By 56 days there were large areas of bone remodeling evidenced by osteoclastic bone resorption and newly formed trabeculae with loss of marrow hematopoietic cells. Subchondral cysts and subchondral sclerosis were present in some rats. In conclusion, intra-articular injection of MIA induces loss of articular cartilage with progression of subchondral bone lesions that mimic those of OA. This model offers a rapid and minimally invasive method to reproduce OA-like lesions in a rodent species.     

The synergistic effects of microfracture, perforated decalcified cortical bone matrix and adenovirus-bone morphogenetic protein-4 in cartilage defect repair

We reported a technique for articular cartilage repair, consisting of microfracture, a biomaterial scaffold of perforated decalcified cortical bone matrix (DCBM) and adenovirus-bone morphogenetic protein-4 (Ad-BMP4) gene therapy. In the present study, we evaluated its effects on the quality and quantity for induction of articular cartilage regeneration. Full-thickness defects were created in the articular cartilage of the trochlear groove of rabbits. Four groups were assigned: Ad-BMP4/perforated DCBM composite (group I); perforated DCBM alone without Ad-BMP4 (group II); DCBM without perforated (group III) and microfracture alone (group IV). Animals were sacrificed 6, 12 and 24 weeks postoperation. The harvested tissues were analyzed by magnetic resonance image, scanning electron microscope, histological examination and immunohistochemistry. Group I showed vigorous and rapid repair leading to regeneration of hyaline articular cartilage at 6 weeks and to complete repair of articular cartilage and subchondral bone at 12 weeks. Groups II and III completely repaired the defect with hyaline cartilage at 24 weeks, but group II was more rapid than group III in the regeneration of repair tissue. In group IV the defects were concave and filled with fibrous tissue at 24 weeks. These findings demonstrated that this composite biotechnology can rapidly repair large areas of cartilage defect with regeneration of native hyaline articular cartilage.     

Tissue engineering-based cartilage repair with allogenous chondrocytes and gelatin-chondroitin-hyaluronan tri-copolymer scaffold: a porcine model assessed at 18, 24, and 36 weeks

We previously showed that cartilage tissue can be engineered in vitro with porcine chondrocytes and gelatin/chondoitin-6-sulfate/hyaluronan tri-copolymer which mimic natural cartilage matrix for use as a scaffold. In this animal study, 15 miniature pigs were used in a randomized control study to compare tissue engineering with allogenous chondrocytes, autogenous osteochondral (OC) transplantation, and spontaneous repair for OC articular defects. In another study, 6 pigs were used as external controls in which full thickness (FT) and OC defects were either allowed to heal spontaneously or were filled with scaffold alone. After exclusion of cases with infection and secondary arthritis, the best results were obtained with autogenous OC transplantation, except that integration into host cartilage was poor. The results for the tissue engineering-treated group were satisfactory, the repair tissue being hyaline cartilage and/or fibrocartilage. Spontaneous healing and filling with scaffold alone did not result in good repair. With OC defects, the subchondral bone plate was not restored by cartilage tissue engineering. These results show that tri-copolymer can be used in in vivo cartilage tissue engineering for the treatment of FT articular defects.     

HA-g-CS Implant and Moderate-intensity Exercise Stimulate Subchondral Bone Remodeling and Promote Repair of Osteochondral Defects in Mice

Background: Substantial evidence shows that crosstalk between cartilage and subchondral bone may play an important role in cartilage repair. Animal models have shown that hydroxyapatite-grafted-chitosan implant (HA-g-CS) and moderate-intensity exercise promote regeneration of osteochondral defects. However, no in vivo studies have demonstrated that these two factors may have a synergistic activity to facilitate subchondral bone remodeling in mice, thus supporting bone-cartilage repair.Questions: This study was to clarify whether HA-g-CS and moderate-intensity exercise might have a synergistic effect on facilitating (1) regeneration of osteochondral defects and (2) subchondral bone remodeling in a mouse model of osteochondral defects.Methods: Mouse models of osteochondral defects were created and divided into four groups. BC Group was subjected to no treatment, HC Group to HA-g-CS implantation into osteochondral defects, ME group to moderate-intensity treadmill running exercise, and HC+ME group to both HA-g-CS implantation and moderate-intensity exercise until sacrifice. Extent of subchondral bone remodeling at the injury site and subsequent cartilage repair were assessed at 4 weeks after surgery.Results: Compared with BC group, HC, ME and HC+ME groups showed more cartilage repair and thicker articular cartilage layers and HC+ME group acquired the best results. The extent of cartilage repair was correlated positively to bone formation activity at the injured site as verified by microCT and correlation analysis. Histology and immunofluorescence staining confirmed that bone remodeling activity was increased in HC and ME groups, and especially in HC+ME group. This bone formation process was accompanied by an increase in osteogenesis and chondrogenesis factors at the injury site which promoted cartilage repair.Conclusions: In a mouse model of osteochondral repair, HA-g-CS implant and moderate-intensity exercise may have a synergistic effect on improving osteochondral repair potentially through promotion of subchondral bone remodeling and generation of osteogenesis and chondrogenesis factors.Clinical Relevance: Combination of HA-g-CS implantation and moderate-intensity exercise may be considered potentially in clinic to promote osteochondral defect repair. Also, cartilage and subchondral bone forms a functional unit in an articular joint and subchondral bone may regulate cartilage repair by secreting growth factors in its remodeling process. However, a deeper insight into the exact role of HA-g-CS implantation and moderate-intensity exercise in promoting osteochondral repair in other animal models should be explored before they can be applied in clinic in the future.     

软骨下钻孔联合软骨源性形态发生蛋白缓释系统修复膝关节软骨缺损

背景：有研究表明软骨源性形态发生蛋白等因子在诱导细胞分化、促进软骨修复过程中起到重要调节作用;软骨下钻孔治疗软骨缺损在临床已广为应用,但其与软骨源性形态发生蛋白等因子联合应用的相关研究至今少有报道。 目的：将软骨下钻孔技术与关节内注射透明质酸/软骨源性形态发生蛋白1缓释载药微球(hyaluronic acid- coated cartilage-derived morphogenetic protein-1,HA/CDMP-1)相结合,观察其对软骨缺损修复的效果,并通过与单纯钻孔组及HA/CDMP-1微球组治疗结果比较,观察两者有无协同效应。 方法：用透明质酸包被软骨源性形态发生蛋白制备缓释微球冻干保存,制备兔实验膝关节全层关节软骨缺损模型,随后将兔随机分为模型组、钻孔组、HA/CDMP-1微球组和钻孔联合HA/CDMP-1微球组,分别采用生理盐水关节腔注射,软骨缺损区钻孔,HA/CDMP-1微球关节腔注射,软骨下钻孔并HA/CDMP-1微球注射。 结果与结论：建模后8,12,16周,组织学观察结果提示,钻孔联合HA/CDMP-1微球组软骨缺损区修复组织覆盖面积明显高于其他3组(P < 0.05);甲苯胺蓝染色和荧光定量PCR检测显示,钻孔联合HA/CDMP-1微球组修复的软骨组织中蛋白多糖和Ⅱ型胶原mRNA的表达明显高于其他3组(P < 0.01或P < 0.05)。结果证实,软骨下钻孔与关节腔内注射HA/CDMP-1联合应用修复兔膝关节软骨缺损近期疗效满意,提示两者可能发生协同作用。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：