自体骨软骨移植与含富集骨髓干细胞松质骨移植修复兔关节软骨缺损

目的:评价自体骨软骨移植与含富集骨髓干细胞松质骨镶嵌移植两种方法修复全层关节软骨缺损的生物学特征和效果。方法:采用新西兰大白兔制作左右后肢全层软骨缺损模型,分别进行自体骨软骨镶嵌移植、含富集骨髓干细胞松质骨镶嵌移植修复,对照组不作任何修复,每组12只。术后第4、8、12周处死动物取材,分别进行膝关节活动度测定、大体观察、光镜观察与电镜观察。结果:移植实验组在第12周时均能以类透明软骨组织修复缺损,对照组为纤维肉芽组织。形态学检查表明,两种方法均能以类透明软骨组织覆盖缺损,骨软骨移植组无明显免疫排斥现象,随着时间延长,修复高度逐渐增加。骨软骨移植组同含富集骨髓干细胞松质骨镶嵌移植组效果无显著差别。结论:骨软骨移植、含富集骨髓干细胞松质骨镶嵌移植两种方法均能以类透明软骨组织修复全层关节软骨缺损,含富集骨髓干细胞松质骨镶嵌移植更适用于较大面积软骨缺损的修复。     

自体骨髓基质干细胞辅助Mosaicplasty技术促进骨软骨缺损修复整合

目的探讨以基于骨髓基质干细胞(BMSCs)的组织工程技术与自体骨软骨柱镶嵌移植术(Mosaicplasty)相结合的方法修复骨软骨及促进缺损间隙的整合效果。方法12只中国山羊于术前2周抽取骨髓,体外培养自体BMSCs。术中以自制器械分别制造山羊双后肢股骨内髁负重区直径5 mm、深3 mm的复合骨软骨缺损各一处。在Mosaicplasty技术填充缺损后,即以动物自体BMSCs与透明质酸凝胶相复合,注射填充于左后肢骨软骨柱之间及与周围组织的间隙内,右后肢单纯自体骨软骨柱移植作为对照组。术后第4、8、16周分别取材进行组织学、组织化学及蛋白聚糖含量等检测。比较16周时两组的缺损区惨复软骨组织与正常软骨的蛋白聚糖含量。结果两组自体骨软骨柱移植软骨均以透明软骨存活,与周围正常软骨间无明显差异。实验组骨软骨柱的间隙内可见新生软骨修复,组织学表现与周围正常软骨相同。交界区整合良好,间隙消失;对照组各时间点软骨间的间隙为纤维组织或纤维软骨填充,仍有间隙存留。移植软骨的基质、实验组骨软骨柱间隙内的新生软骨基质及Ⅱ型胶原免疫组化染色均为阳性。蛋白聚糖含量比较显示,对照组骨软骨柱间隙内新生组织的蛋白聚糖含量均低于正常软骨和实验组,差异有显著性意义(P< 0．05)。结论基于BMSCs的组织工程技术结合Mosaicplasty技术,可以有效地促进骨软骨缺损间隙的整合,改善修复效果好,有望成为一种理想的促进骨软骨缺损修复的方法。     

自体柱状骨软骨移植修复股骨头软骨缺损的实验研究

目的探讨用自体股骨头非负重区骨软骨移植修复股骨头负重区软骨缺损。方法选用成年杂种犬18只,36个髋关节股骨头,随机抽取2只动物4个股骨头作为正常对照。分别凿取股骨头负重区及非负重区相同柱状骨软骨换位移植,于术后4、8、12、24及48周进行大体观察、组织学检查、电镜观察、CT、ECT及MRI检查。结果实验组移植后的骨软骨存活,骨软骨色泽及组织学检测显示移植的软骨细胞、骨细胞形态与正常对照组比较无显著差异,电镜观察显示其成骨细胞、骨细胞及软骨细胞与正常对照组无明显差异。结论股骨头非负重区骨软骨修复股骨头负重区软骨缺损,能达到骨愈合及修复软骨缺损的目的。     

自体骨软骨移植修复软骨缺损的研究

把非负重区正常软骨移植到负重区病损软骨部位，让其在受区发挥作用、改善关节功能、减轻患者痛苦是目前研究的热点。拟在关节镜监视下，取非负重区软骨自体移植替代负重区病变软骨．探讨自体骨软骨移植修复软骨缺损的可行性、效果及并发症。     

同体骨软骨镶嵌移植术修复关节软骨病损

目的　探讨同体同关节内骨软骨镶嵌式移植 ,治疗关节软骨病损的可行性。方法　采用美国镶嵌式骨软骨移植器 ,通过开放或关节镜下进行同关节非负重关节面提供骨软骨移植条块修复关节负重面的软骨病损。结果　手术 6例 ,术后随访 5～ 9个月 ,平均 6个月 ,均达到优良效果。结论　同体关节骨软骨镶嵌移植对治疗关节应力性局灶性软骨病、创伤性软骨缺损的45岁以下病人是一个效果确实、值得推广的方法     

自体骨软骨移植修复距骨软骨或骨软骨缺损

目的探讨从同侧膝关节非负重面获取骨软骨柱,行自体移植修复距骨穹窿部局限性软骨或骨软骨缺损的临床效果。方法23例距骨穹窿部软骨病损的患者,包括创伤后软骨缺损11例,剥脱性骨软骨炎9例和局灶性骨关节炎3例。踝关节镜下明确缺损的部位、大小,行关节镜下或加用关节切开移植术,缺损区清创后钻孔,自同侧膝关节非负重区钻取骨软骨小柱,利用骨软骨自体移植系统(osteochondralautografttransfersystem,OATS)的专用器械,采取压配固定技术将移植物植入受区的孔中,行单柱或多柱镶嵌式移植修复距骨软骨缺损。结果术后随访15～30个月,平均22个月。利用标准VAS(visualanaloguescale)尺子评估踝关节疼痛程度,评分从术前平均4.9±1.2降至术后0.8±0.1(P<0.001)。测量踝关节跖屈和背伸角度,关节活动范围由术前平均44.3°±5.8°增加到术后65.6°±11.2°(P<0.001)。按Mazur等方法综合评定踝关节的状况,评分从术前平均(51.7±8.6)分提高到(92.4±6.3)分(P<0.001)。术后MR检查提示修复的关节面平滑,移植物与周围组织结合良好。结论以同侧膝关节非负重区的骨软骨移植修复距骨局限性软骨或骨软骨缺损是一种疗效明显的外科手术方法。     

同体骨软骨镶嵌移植术修复关节软骨病损

目的：探讨同体同关节内骨软骨镶嵌式移植，治疗关节软骨病损的可行性。方法：采用美国镶嵌式骨软骨移植器，通过开放或关节镜下进行同关节非负重关节面提供骨软骨移植条块修复关节负重面的软骨病损。结果：手术6例，术后随访5-9个月，平均6个月，均达到优良效果。结论：同体关节骨软骨镶嵌移植对治疗关节应力性局灶性软骨病、创伤性软骨缺损的45岁以下病人是一个效果确实、值得推广的方法。     

自体镶嵌式骨软骨移植治疗伴局灶性软骨缺损的膝骨性关节炎

目的探讨自体镶嵌式骨软骨移植修复膝骨性关节炎负重区局灶性软骨缺损的可行性和疗效。方法2004年1月～2006年11月,对19例伴局灶性软骨缺损的膝骨性关节炎采用自体镶嵌式骨软骨移植技术治疗,在关节镜下行非负重区自体骨软骨移植修复软骨缺损,术后给予中药口服、玻璃酸钠关节腔注射,6周下地部分负重。定期随访,根据改良Lysholm评分标准、关节液蛋白多糖(PG)、膝关节MRI评价疗效。结果术后获随访12～34(平均24个月)个月,患者疼痛基本消失,功能良好。术前改良Lysholm评分15～63(39.7±4.6)分,术后54～100(93.1±5.9)分,有显著性差异(P<0.01)。术前关节液蛋白多糖215.5～897.3(508.8±203.6)μg/L,术后80.4～571.6(263.5±141.2)μg/L,治疗前后相比,差异有统计学意义(P<0.05)。术后复查MRI示原缺损区软骨表面光滑,移植的软骨下骨愈合良好,总有效率94.8。结论关节镜下自体骨软骨移植创伤小,结合中药口服、玻璃酸钠关节腔注射是治疗伴软骨缺损的膝骨性关节炎的有效方法。     

脱细胞骨软骨支架复合自体骨髓间充质干细胞修复羊骨软骨缺损的研究

目的探讨脱细胞骨软骨支架接种自体骨髓间充质干细胞(BMSCs)修复羊骨软骨缺损效果,探索骨软骨缺损新的修复方式。方法制备直径为8mm骨软骨脱细胞支架,培养羊BMSCs,接种于骨软骨支架,制备羊负重区骨软骨缺损模型,分空白、空白支架及细胞支架复合物3组,每组4只羊,3个月后处死动物取标本行大体及组织学检测。结果修复羊负重区骨软骨缺损模型实验结果显示细胞支架复合修复组骨软骨有较好修复,空白支架组软骨下骨基本修复、软骨侧无明显修复,空白对照组未见明显修复,缺损边缘软骨退变。结论含骨软骨连接结构的脱细胞骨软骨支架接种种子细胞能较好的修复羊负重区骨软骨缺损。     

自体骨软骨镶嵌移植术修复关节软骨缺损

目的：回顾性分析关节镜下自体骨软骨镶嵌式移植术治疗负重面关节软骨损伤的可行性。方法：采用Smith Nephew镶嵌式骨软骨移植器，在关节镜下挖取膝关节非负重关节面骨软骨条，并将之移检修复膝关节负重面的局灶性软骨缺损。结果：手术15例，术后随访7—12个月，平均9个月，均达到优良效果。结论：自体关节骨软骨镶嵌移植术对关节负重面局灶性软骨缺损有较好、确实的治疗效果。     

Ingrowth of osteochondral grafts under the influence of growth factors: 6-month results of an animal study

Introduction: In the age of growth factors and gene therapy, the induction of cartilage healing remains an unsolved problem. Even in autologous grafting, one of the preferred methods of treatment for focal osteochondral lesions, chondral integration remains difficult. This study aims to define a possible positive influence of growth factor augmentation on the ingrowth of these transplants. Materials and methods: In an ovine model, questions regarding the healing of osteochondral transplants under the influence of two different growth factors were to be addressed. Two osteochondral autologous transplantations (OAT), one in the weight-bearing surface of each femoral condyle, were performed on the ovine knee using the standard operative protocol. One of the grafts was bathed in augmented PBS containing 50 μg bFGF or bone morphogenetic protein (BMP)-2 directly prior to implantation, while the other condyle served as the control. Two groups, consisting of eight sheep each, were evaluated for each growth factor after 6 months. Results: During the evaluation of all the specimens, neither osteophytes nor synovial changes were observed. The mechanical consistency of the cartilaginous tissue began to reach a level equivalent to the surrounding tissue at 6 months, independent of the use of growth factor. Macroscopically, the superficial border of the transplanted osteochondral plug could easily be outlined in all groups, while the cartilage interface of the bFGF specimens was determined to be less demarcated than the BMP augmented plugs or the controls. Radiographically, a solid osteointegration of the graft could be documented at 6 months in the native and augmented groups. In contrast, integration of the chondral surface of the OAT was not seen macro- or microscopically in any specimen, even though cartilage surfaces remained viable. A firm physical interdigitation of the reconstructed joint surface could not be demonstrated in either of the two augmented groups or the control population. The augmentation with bFGF and BMP-2 stimulated the osseous ingrowth and seems to expedite the remodelling process, but was not able to improve chondral healing. Conclusion: The lack of integration of the cartilaginous portion of the transplanted plugs into the reconstructed joint surface, even following the augmentation with bFGF and BMP-2, does not bode well for the long-term survival of the joint itself.     

Contact pressure comparison of proud osteochondral autograft plugs versus proud synthetic plugs

Osteochondral autograft transfer is an accepted treatment for chondral and osteochondral defects of the knee. Synthetic plugs may eventually be used for primary treatment of defects. Currently they are largely used for osteochondral donor site backfill. Placement of osteochondral or synthetic plugs proud leads to articulating surface incongruity, increases in contact pressure, and potential for both plug and opposing surface degenerative change. We conducted a biomechanical study of human cadaver knees to determine whether differences exist in the contact pressure of osteochondral autograft plugs placed proud versus synthetic plugs placed proud. Ten human cadaveric knees were used (20 condyles). Contact pressure was measured with Tekscan sensor technology (South Boston, Massachusetts) with both static and cyclical loads (of 250 and 500 cycles) created by an MTS Bionix system (Eden Prairie, Minnesota) under the following conditions: native articular cartilage, surgically created defect (7-mm diameter), 1-mm proud osteochondral autograft, and 1-mm proud synthetic graft. Proud osteochondral autograft plugs resulted in a 21.4% increase in peak contact pressure over surrounding native articular cartilage versus a 4.9% increase with proud synthetic plugs. Synthetic plugs compressed their structure and subsided versus subchondral bone collapse with compressive load in osteochondral autograft plugs. Proud osteochondral autograft plugs have significantly higher peak contact pressures than proud synthetic plugs when placed for treatment of chondral and osteochondral defects in the knee.     

Alendronate prevents collapse in mechanically loaded osteochondral grafts: a bone chamber study in rats

BACKGROUND: Subchondral bone necrosis is important in osteonecrosis, Mb Kienboeck, intraarticular fractures or osteochondral grafting. As revascularization follows, bone resorption may lead to collapse in load bearing areas during the remodeling. Bisphosphonates are potent osteoclast inhibitors. Our hypothesis was that local bisphosphonate treatment of an osteochondral graft, in a high load environment, would protect the subchondral bone from collapse and maintain the joint architecture during remodeling. To investigate this, we used a rat bone chamber model to subject a necrotic osteochondral graft to a large mechanical load during remodeling. METHOD: Cylindrical osteochondral grafts were taken from the patellar groove of rats, one end of the cylinder being the joint surface. The grafts were frozen, thawed and treated with alendronate. The length of the cylinder was measured and the grafts were placed in the chambers, which were inserted into the proximal tibia of rats. The chambers were left to heal in for two weeks to allow establishment of a vascular supply, and then the transplanted osteochondral plugs were mechanically loaded for 4 weeks, once a day with 10 cycles of 2 MPa pressure at 0.16 Hz. RESULTS: At harvest, the graft length had decreased during remodeling in 5 of the 6 untreated controls, but only in 2 out of 8 alendronate-treated rats (p = 0.05). Histologically, the bone graft in the non-treated controls was resorbed in the remodeled part of the graft, whereas in the alendronate-treated rats a dense trabecular bone was found consisting of both new bone and graft. INTERPRETATION: Local treatment of the graft with bisphosphonate diminishes the risk of collapse during revascularization and bone remodeling in a mechanically loaded osteochondral graft. This could be useful in a variety of situations when bone remodeling occurs after a necrosis close to a joint, either spontaneously after osteonecrosis or a fracture, or after surgical procedures such as mosaic-plasty or other osteochondral grafting.     

Healing of osteochondral transplants--animal experiment studies using a sheep model

AIM: Autologous grafting has developed into one of the preferred methods of treatment for focal osteochondral lesions, although basic research on this topic remains sparse. In an animal study, questions regarding the healing of such osteochondral transplants are clarified. METHOD: An autologous osteochondral transplantation was performed on the ovine knee using the standard operative protocol. Two groups, consisting of 10 sheep each, were evaluated after 3 and 6 months, respectively. RESULTS: During the clinical evaluation of the specimens, neither osteophytes nor synovial changes were observed. The consistency of the cartilaginous tissue began to reach a level equivalent to the surrounding tissue only after 6 months. Macroscopically, the superficial border of the transplanted osteochondral plug could easily be outlined at both time points. Radiographically, a solid osteointegration of the graft could already be documented at 3 months. In contrast, integration of the chondral surface of the OAT was not seen macro- or microscopically at any point in time. A firm physical interdigitation of the reconstructed joint surface could not be demonstrated. CONCLUSIONS: The lack of integration of the cartilaginous portion of the transplanted plugs into the reconstructed joint surface leads to questions regarding the long-term survival of the joint itself.     

Osteochondral autologous transplantation in various joints

A chondral/osteochondral defect involving the articular surface of a joint is still a therapeutic problem. The goal of articular cartilage repair is restoration of cartilage congruity, accomplishing full painfree range of motion and elimination of cartilage detoriation. The use of autologous grafts was first reported by Wagner 1964. Now the use of cylindrical autograft plugs was described by Bobic 1996 and Hangody 1996. Operative management and early results of osteochondral cylindrical autograft plugs in the femoral condyle, patella, elbow and talar dome are presented. The arthroscopic/open use of autologous osteochondral grafts from the knee is indicated in osteochondral lesions in diameter from 1 to 3 cm, which can not be primarily refixed and in osteonecrosis at femoral condyle, patella, elbow, talar dome as well as shoulder.     

The effect of fibroblast growth factor-2 on autologous osteochondral transplantation

In this study, we performed a mechanical analysis of the effect of fibroblast growth factor-2 (FGF-2) on autologous osteochondral transplantation in a rabbit model. A full-thickness cartilage defect (diameter: 5 mm; depth: 5 mm) made in the right femoral condyle was treated with osteochondral transplantation using an osteochondral plug (diameter: 6 mm; depth: 5 mm) taken from the left femoral condyle. The animals were divided into three groups: Group I, the defect was filled with 0.1 ml of gelatin hydrogel containing 1 microg of FGF-2; Group II, the defect was filled with 0.1 ml of gelatin hydrogel only; Group III, the defect was left untreated. Thereafter, osteochondral plugs were transplanted and the transplanted osteochondral grafts were evaluated mechanically and histologically at postoperative weeks 1, 3, 8 and 12. The structural property of the osteochondral graft was significantly greater in Group I than in Groups II and III at postoperative week 3. Histological analysis at 3 weeks revealed a tendency towards increased subchondral bone trabeculae in Group I compared with the other groups. Autologous osteochondral grafts transplanted with gelatin hydrogel containing FGF-2 acquired adequate stiffness at an early postoperative phase.     

A morphologic,biochemical, and biomechanical assessment of short-term effects of osteochondral autograft plug transfer in an animal model

Purpose: The objective of this study was to assess the short-term changes that occur after an osteochondral autograft plug transfer from the femoral trochlea to the medial femoral condyle in a goat model. Type of Study: Articular cartilage repair animal study. Methods: Six adult male goats were used in this study. Two 4.5-mm osteochondral plugs were transferred from the superolateral femoral trochlea to 2 recipient sites in the central portion of the medial femoral condyle for a survival period of 12 weeks. Postmortem, the global effects of the procedure were assessed by gross morphologic inspection and by analyzing the synovial DNA for inflammatory response. The recipient sites were also evaluated histologically and biomechanically. Metabolic activity was determined by ³⁵SO₄ uptake, and viability was assessed using a live/dead stain and by confocal laser microscopy. Results: There was no evidence of significant gross morphologic or histologic changes in the operative knee as a result of the osteochondral donor or recipient sites. The patella, tibial plateau, and medial meniscus did not show any increased degenerative changes as a result of articulating against the donor or recipient sites of the osteochondral autografts. Analysis of synovial DNA revealed no inflammatory response. Biomechanically, 6- to 7-fold greater stiffness was noted in the cartilage of the transferred plugs compared with the control medial femoral condyle. Furthermore, on histologic examination, the healing subchondral bone interface at the recipient site had increased density. Glycosaminoglycan synthesis as determined by ³⁵SO₄ uptake was upregulated in the transplanted cartilage plug relative to the contralateral control, showing a repair response at the site of implantation. And finally, confocal microscopy showed 95% viability of the transferred plugs in the medial femoral condyle region. Conclusions: Our findings demonstrate the ability to successfully transfer an osteochondral autograft plug with maintenance of chondrocyte cellular viability. The transferred cartilage is stiffer than the control medial femoral condyle cartilage, and there is concern regarding the increased trabecular mass in the healing subchondral plate, but these do not result in increased degenerative changes of the opposing articular surfaces in the short term.Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 17, No 8 (October), 2001: pp 856–863     

Antegrade nailing in femoral shaft fracture patients - comparison of outcomes of isolated fractures,multiple fractures and severely injured patients

Introduction: Femoral shaft fractures in adults are high-energy fractures typically accompanied by additional fractures of the upper and lower extremities and brain, thoracic, or abdominal injuries. Intramedullary nailing enables early ambulation with a few complications, but rates of non-union remain high. Therefore, we aimed to compare bone union after femoral shaft fractures in adults (20–65 years old) depending on the injury severity and presence of multiple fractures.Patients and methods: This study retrospectively examined 178 patients (145 male and 33 female) who underwent intramedullary nailing for a femoral shaft fracture (Arbeitsgemeinschaft für Osteosynthesefragen/Orthopedic Trauma Association 32 type) between January 2014 and December 2018 and were followed up for at least 1 year. Patients who underwent intramedullary nailing after the preliminary application of an external fixator were excluded. Patients were divided into groups with isolated femoral shaft fractures (IS group), an injury severity score of ≤14, and multiple fractures of the extremities and the pelvic bone (at least three locations), including a femoral shaft fracture (MU group), and severely injured (injury severity score ≥15) with femoral shaft fractures (SE group). Non-union rate by group and risk factors related to bone union and bone union rate according to time to full weight bearing were analyzed.Results: In total, 29, 54, and 95 patients were assigned to the IS group, MU group, and SE group, respectively. Non-union was observed in two patients in the IS group (6.9%), six patients in the MU group (11.1%), and 11 patients in the SE group (11.6%). There were no significant differences in the bone union rate, according to multiple fractures (p=0.515) and injury severity score (p=0.561). Additionally, no differences in the bone union rate were observed according to the time to full weight bearing. Depending on open fracture (p=0.004) and fracture severity (p=0.011), the non-union rate showed a difference of up to four times or greater.Conclusions: When intramedullary nailing is performed to treat femoral shaft fractures, multiple fractures and severe trauma do not directly affect bone union. However, it should be noted that open fracture and greater fracture severity lead to higher chances of non-union.     

Healing of osteochondral grafts in an ovine model under the influence of bFGF

Purpose: The well-recognized limitations in cartilage healing have lead to the development of a number of resurfacing techniques for defects of joint surfaces. Autologous grafting has developed into 1 of the preferred methods of treatment for focal osteochondral lesions, although basic research on this topic remains sparse. Type of Study: In an animal study, questions regarding the healing of osteochondral transplants under the influence of basic fibroblast growth factor (bFGF) were addressed. Methods: Two osteochondral autologous transplantations (OAT), 1 in the weight-bearing surface of each femoral condyle, were performed on the ovine knee using a standard operative protocol. One of the grafts was bathed in phosphate buffered sulfate (PBS) containing 50 μg of recombinant human bFGF (rh-bFGF) directly before implantation. Two groups consisting of 10 sheep each were evaluated after 3 and 6 months, respectively. Results: During the evaluation of the specimens, neither osteophytes nor synovial changes were observed. Macroscopically, the superficial border of the transplanted osteochondral plug could easily be outlined at both time periods, even though the cartilage interface of the rh-bFGF specimens was less demarcated. Radiographically, a solid osteointegration of the graft could already be documented at 3 months in the control group. In contrast, integration of the chondral surface of the OAT was not seen macroscopically or microscopically at any point. A firm physical interdigitation of the reconstructed joint surface could not be demonstrated in either of the 2 groups. The augmentation with rh-bFGF stimulated the osseous ingrowth, but was not able to improve chondral healing. Conclusions: The lack of integration of the cartilaginous portion of the transplanted plugs into the reconstructed joint surface, even following augmentation with bFGF, leads to questions regarding the long-term survival of the joint itself.Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 19, No 2 (February), 2003: pp 182–187