Development of transplanted fetal bones: differences between isografts and allografts in mice

Allogeneic bone from bone banks frequently is used when large skeletal defects have to be bridged in orthopaedic surgery. Beside immunologic rejection of the graft, the loss in osteogenic potential caused by bone banking procedures may be a major reason for limited clinical success. Similar problems as described for bone have occurred with cartilage and osteochondral transplants. Improving the properties of allogenic bone so that its biologic activity becomes comparable to autologous bone could be substantially beneficial for the outcome of allograft transplantation. To dissect the steps involved in the integration of a fetal osteochondral graft as it matures to bone, the current study compared the development and biologic function of metatarsals from 18-day-old fetal mice freshly transplanted in three different immunologic settings. Morphologic assessment of (1) isografts and (2) allografts in nonsensitized hosts 12 days after transplantation revealed that the grafts bear an intrinsic potential to develop after transplantation. In allografts in nonsensitized hosts, however, a slight alteration in biologic activity as compared with isografts could be detected already in this early phase after transplantation by in situ hybridization for messenger ribonucleic acids encoding extracellular matrix proteins. (3) In contrast to isografts and allografts in nonsensitized hosts, morphologic features and biologic function of allografts transplanted to presensitized hosts were altered severely.     

Focal osteochondral necrosis of the femoral head of an adult after Legg-Calve-Perthes disease in childhood

In the treatment of circumscribed osteochondral lesions of the knee and the ankle joint autologous osteochondral transplantation (AOT) has been established as one of the possible operative therapies. However, there is less experience with the use of AOT on other joints (shoulder, elbow). The care of osteochondral defects of the hip joint with autologous osteochondral transplantation can still be regarded as an absolute rarity. Facing a focal osteochondral necrosis in a young female adult after LCP disease in childhood, we report about an autologous osteochondral transplantation at the femoral head using the diamond bone cutting system.     

Editorial Commentary: Osteochondral Allografting Is a “Kid-Friendly” Cartilage Repair Procedure

Fresh osteochondral allograft transplantation has been my preferred procedure for chondral and osteochondral lesions for many decades. This is particularly true for patients younger than 18 years of age, where diagnoses such as osteochondritis dissecans, osteochondral fractures, and osteonecrosis predominate, rendering the situation as much a “bone problem” as a “cartilage problem.” In the universe of cartilage-repair techniques, osteochondral allografts are particularly useful when bone defects must be managed. Furthermore, allografts have stood the test of time for safety, efficacy, and durability, even in a young, active population. For me, I don't think twice about using fresh allografts in young patients. I might even have to admit that an osteochondral allograft transplantation procedure for an osteochondritis dissecans lesion in a patient younger than 18 years old is my favorite surgery!     

Autologous osteochondral transplantation

The surface of diarthrodial joints is covered by hyaline cartilage whose regeneration capacity is extremely limited. Conventional surgical techniques enable repair of full-thickness articular cartilage defects only by fibrous cartilage having poor mechanical properties. Recently, new techniques have been developed to provide hyaline or hyaline-like repair tissue in the treatment of full-thickness cartilage defects. Autologous osteochondral transplantation involves press-fit implantation of both bone and cartilage obtained from healthy articular surface. The principal indication for this technique is unifocal full-thickness chondral or osteochondral defects measuring 1 to 4 square centimeters. This surgical procedure can be performed openly or arthroscopically. The graft should be placed vertically and evenly to the joint surface. Although short-term and mid-term results are satisfactory, several problems have been reported including donor site morbidity, damage to cartilage, and incongruity and incorporation of the graft. Autologous osteochondral transplantation provides viable osteochondral units at a single stage and eliminates the need for culturing chondrocytes which is quite expensive. Currently, no surgical technique or medical treatment provide complete healing of articular cartilage defects. Autologous osteochondral transplantation is an important stage worthy of improvement in this respect.     

Treatment of focal osteochondral defects of the acetabulum with osteochondral allograft transplantation

To our knowledge, treatment of focal osteochondral defects of the acetabulum with osteochondral allograft transplantation has not been described. As with osteochondral lesions of other weight-bearing surfaces, these defects may lead to disabling pain and early degenerative changes. In older patients who fail nonoperative treatment, hip arthroplasty is a reliable option to obtain pain relief and restore function. However, in young and active patients, it may be advantageous to restore joint congruity biologically. The clinical success of osteochondral allograft transplantation in the femoral condyles has been well-documented, with over 25 years of experience. We propose similar treatment principles in the hip joint.This article presents the cases of a 24-year-old woman (patient 1) and a 32-year-old man (patient 2) with hip pain and dysfunction secondary to a focal osteochondral defect of the acetabulum. Both were treated with osteochondral allograft transplantation to the defect using a dowel technique. A magnetic resonance image at 18 months in both cases demonstrated incorporation of the allograft bone into the host acetabulum. At 24 months in patient 1 and 42 months in patient 2, radiographs showed no progressive osteoarthritis. Both patients' Hip Outcome Scores were 100 points each.Osteochondral allografts allow large areas to be resurfaced without donor site morbidity, and these grafts provide an immediate functional joint surface. Although it has not been proven in terms of long-term follow-up, we believe that osteochondral allograft transplantation for focal osteochondral defects of the acetabulum in young, active patients is a feasible option to restore joint congruity.     

Immune responses to osteochondral allografts. Current knowledge and future directions

Immune responses directed against osteochondral allograft-associated immunogens have been demonstrated in a variety of animals models and, to a more limited degree, in human recipients. The most extensively studied, and presumably the most potent source of sensitization, are cell-surface transplantations found on the heterogeneous cell types ubiquitous to skeletal tissues. By virtually all criteria used for evaluation, the immunogenicity resulting from histocompatibility antigens is reduced by deep-freezing the allograft prior to implantation, and responses are diminished even further when tissues are freeze-dried. There is preliminary evidence to suggest that matrix components, particularly proteoglycan subunits, are also capable of sensitizing osteochondral graft recipients. The magnitude and significance of these immunogens are matters of speculation. Collagen may also act as an osteochondral allograft immunogen. The significance of osteochondral allograft immunogenicity, as compared with biomechanical factors in the incorporation of a bone graft, has not yet been elucidated. The effect of immune responses on clinical allograft success, if it is as important as it appears, should profoundly influence future osteochondral allograft research in reconstructive joint surgery.     

带旋髂深血管蒂髂骨与骨软骨联合移植治疗股骨头坏死

目的 探讨带血管蒂髂骨与自体柱状骨软骨联合移植治疗股骨头坏死(osteonecrosis of the femoral head,ONFH)的疗效及临床应用价值.方法 自2001年11月至2007年5月,采用带血管蒂髂骨与自体柱状骨软骨联合移植治疗ONFH患者13例(13髋),均为男性;年龄26-43岁,平均34.3岁.左侧7髋,右侧6髋.激素性ONFH 9例,股骨颈骨折内固定术后ONFH 4例.按国际骨循环研究学会分期,ⅢA期2例,ⅢB期4例,ⅢC期7例;术后3个月、6个月及每年X线片检查双髋正位及轴位片,必要时行CT或MR检查.采用Harris评分评价髋关节功能.结果 13例患者全部获得门诊随访,随访时间1.5-6.0年,平均(2.4±0.4)年.X线片和CT示,术后3个月可见植入的骨软骨柱和髂骨瓣轮廓,但与周围骨质界限模糊;股骨头内密度不均匀,股骨头外形不规则.术后1-2年.骨软骨柱及髂骨瓣与周围骨愈合良好,股骨头塌陷区不同程度恢复高度2-5 mm,平均(3.1±1.6)mm,囊性变消失或变小.术后1年影像学好转率为100%;Harris评分从术前平均(54.7±7.6)分提高到平均(81.8±13.5)分,差异有统计学意义.结论 带旋髂深血管蒂髂骨与骨软骨联合移植技术治疗青壮年中晚期ONFH患者可获得良好的近期疗效,中远期疗效有待进一步观察.     

Abwägung oder doch harte Kriterien in der Begutachtung von Läsionen der distalen Bizepssehne

Osteochondritis dissecans, transchondral and osteochondral fractures are collectively known under the generic term osteochondral lesions of the talus. The etiology of the aseptic bone necrosis still remains unclear. Osteochondritis dissecans often requires additional radiological diagnostics by conventional X?ray imaging in two planes and subsequent cross-sectional imaging in cases of unspecific clinical symptoms. The classification of Berndt and Harty with modifications for computed tomography and magnetic resonance imaging has been preoperatively proven. Asymptomatic lesions and stage I and II lesions are treated conservatively. Stage III lesions or persistance of symptoms after 6 months of conservative treatment require a surgical procedure in the form of bone marrow stimulation techniques or chondrocyte transplantation. Small defects without subchondral involvement are ideal for microfracturing, whereas subchondral cysts and medium sized defects are treated by osteochondral autograft transplantation. Autologous chondrocyte transplantations are used for large defects with intact subchondral bone. Currently, there are no valid evidential recommendations for the treatment of osteochondritis dissecans.     

Arthroscopic Glenoid Osteochondral Allograft Reconstruction Without Subscapularis Takedown: Technique and Literature Review

Failure to address glenoid deficiency/osteochondral defects can lead to persistent shoulder instability despite a surgical stabilization procedure. In patients with significant glenoid bone loss, osteoarticular allograft transplantation has the potential benefit of restoring normal glenohumeral anatomy. It may also reduce the risk of recurrent instability and permit near-normal postoperative range of motion while avoiding the complications of nonanatomic reconstruction techniques. Numerous open methods of anatomic glenoid reconstruction have been described, including the use of iliac crest autograft, distal tibia allograft, and glenoid allograft. Our purpose is to review the literature regarding the surgical treatment of glenoid bone deficiency. We also describe a novel technique of arthroscopic anteroinferior glenoid reconstruction using glenoid osteochondral allograft without subscapularis takedown. The potential risks and benefits of our technique are also discussed.     

Treatment of osteochondral defects of the distal femur with fresh osteochondral allografts: A preliminary report

Twenty-four patients with osteochondral defects of a femoral condyle who failed to respond adequately to arthroscopic arthroplasty underwent osteochondral grafting with fresh allografts. Grafts were obtained from young donors and were matched according to skeletal size as measured by standard x-rays. Transplantation was performed within 12 h of harvesting. Follow-up extends from 2 to 4 years in 10 cases and is 1-2 years in the remaining 14. All ten patients with follow-up greater than 2 years were improved when evaluated in terms of pain, buckling, and swelling. Of the 24 patients, 11 have been evaluated arthroscopically following transplantation. In all 11 cases, the graft appeared viable. Fraying, if present, was limited to the margins of the graft in all except two cases. Collapse was not observed.     

Reconstruction of skeletal deficits at the knee. A comprehensive osteochondral transplant program

From 1971 to 1982, 110 osteochondral transplants with follow-up evaluation were performed for treatment of skeletal deficits caused by degenerative, traumatic, and neoplastic diseases largely involving the knee joint. Seventy-eight small-fragment fresh allografts were transplanted for repair of old tibial plateau osteochondral fractures, osteonecrosis, and unicompartmental osteoarthritis. Thirty-two large-fragment grafts were performed following en bloc excision of bone tumors. Of these, 22 were allografts, three were vascularized fibular autografts, and seven were a combination of allografts and vascularized fibular autografts. In this large-fragment group, three grafts have been removed for tumor recurrence, two for infection, and one for a stress fracture. The results of these transplants have proved particularly rewarding in the old plateau fractures, for traumatic loss of bone and cartilage (osteonecrosis), and after en bloc excision of giant cell tumors.     

Inactivation of Vhl in Osteochondral Progenitor Cells Causes High Bone Mass Phenotype and Protects Against Age‐Related Bone Loss in Adult Mice

Previous studies have shown that disruption of von Hippel–Lindau gene (Vhl) coincides with activation of hypoxia‐inducible factor α (HIFα) signaling in bone cells and plays an important role in bone development, homeostasis, and regeneration. It is known that activation of HIF1α signaling in mature osteoblasts is central to the coupling between angiogenesis and bone formation. However, the precise mechanisms responsible for the coupling between skeletal angiogenesis and osteogenesis during bone remodeling are only partially elucidated. To evaluate the role of Vhl in bone homeostasis and the coupling between vascular physiology and bone, we generated mice lacking Vhl in osteochondral progenitor cells (referred to as Vhl cKO mice) at postnatal and adult stages in a tamoxifen‐inducible manner and changes in skeletal morphology were assessed by micro–computed tomography (µCT), histology, and bone histomorphometry. We found that mice with inactivation of Vhl in osteochondral progenitor cells at the postnatal stage largely phenocopied that of mice lacking Vhl in mature osteoblasts, developing striking and progressive accumulation of cancellous bone with increased microvascular density and bone formation. These were accompanied with a significant increase in osteoblast proliferation, upregulation of differentiation marker Runx2 and osteocalcin, and elevated expression of vascular endothelial growth factor (VEGF) and phosphorylation of Smad1/5/8. In addition, we found that Vhl deletion in osteochondral progenitor cells in adult bone protects mice from aging‐induced bone loss. Our data suggest that the VHL‐mediated signaling in osteochondral progenitor cells plays a critical role in bone remodeling at postnatal/adult stages through coupling osteogenesis and angiogenesis. © 2014 American Society for Bone and Mineral Research.     

Treatment principles for osteochondral lesions in foot and ankle

Osteochondral lesion of the talus (OLT) is a broad term used to describe an injury or abnormality of the talar articular cartilage and adjacent bone. A variety of terms have been used to refer to this clinical entity, including osteochondritis dissecans (OCD), osteochondral fracture and osteochondral defect. Whether OLT is a precursor to more generalised arthrosis of the ankle remains unclear, but the condition is often symptomatic enough to warrant treatment. In more than one third of cases, conservative treatment is unsuccessful, and surgery is indicated. There is a wide variety of treatment strategies for osteochondral defects of the ankle, with new techniques that have substantially increased over the last decade. The common treatment strategies of symptomatic osteochondral lesions include nonsurgical treatment, with rest, cast immobilisation and use of nonsteroidal anti-inflammatory drugs (NSAIDs). Surgical options are lesion excision, excision and curettage, excision combined with curettage and microfracturing, filling the defect with autogenous cancellous bone graft, antegrade (transmalleolar) drilling, retrograde drilling, fixation and techniques such as osteochondral transplantation [osteochondral autograft transfer system (OATS)] and autologous chondrocyte implantation (ACI). Furthermore, smaller lesions are symptomatic and when left untreated, OCDs can progress; current treatment strategies have not solved this problem. The target of these treatment strategies is to relieve symptoms and improve function. Publications on the efficacy of these treatment strategies vary. In most cases, several treatment options are viable, and the choice of treatment is based on defect type and size and preferences of the treating clinician.     

Autologous chondrocyte transplantation of the ankle

Autologous chondrocyte transplantation has been used in the treatment of chondral and osteochondral lesions in a limited number of patients. The results are promising over a medium-length follow-up (2-6 years). Deeper involvement of the subchondral bone may need autologous bone grafting along with ACT. Future long-term, comparative studies are needed to evaluate the efficacy and safety of the treatment.     

距骨骨软骨损伤的治疗研究进展

距骨骨软骨损伤是运动医学中具有挑战性的疾病之一。临床治疗策略包括保守治疗和手术治疗,保守治疗在儿童患者中效果最佳,对于成人患者常常选择进行手术治疗。目前常见的外科手术治疗方案包括关节镜下骨髓刺激、自体软骨细胞植入、自体骨软骨移植、同种异体骨软骨移植或同种异体青少年软骨微粒移植等。关节镜下骨髓刺激技术(特别是微骨折)适用于较小的病灶,是常见的一线治疗方案,中短期临床疗效令人满意,但长期疗效有待进一步观察。自体骨软骨移植常用于伴有较大囊性病变的距骨骨软骨损伤患者,有着较好的中短期临床疗效,然而术后存在囊肿复发和供区并发症的发生。近年来有大量文献报道其他生物治疗措施,如骨软骨损伤区域注射富含血小板血浆、或者浓缩骨髓细胞等,均有一定的临床疗效。本文对这些技术的应用细节和疗效进行综述,目的是为临床医生能够更好地治疗距骨骨软骨损伤提供依据。     

Surgical Treatment of an Osteochondral Lesion Associated with Stress Fracture of the Tarsal Navicular: A Case Report

We surgically treated an osteochondral lesion associated with a stress fracture of the tarsal navicular. The surgical procedure involved the confirmation and complete resection of the lesion under direct vision, followed by the transplantation of block-shaped iliac bone grafts. The postoperative computed tomography scan showed that the lesions had disappeared, the grafted bone had fused, and the stress fracture had healed. However, the tarsal navicular joint surface was slightly irregular. The patient was able to resume her sports activities 15 weeks after surgery. We have described a novel method to reconstruct the tarsal navicular after osteochondral lesion resection.     

Repair of cartilage defects in the knee

The factors to be considered in selecting a technique are the diameter of the chondral defect, the depth of the bone defect, and the knee alignment. As a rough guide, I suggest the following guide to treatment. Chondral defects (without bone involvement) <3 cm in diameter can be treated with microfracture, autologous chondrocyte transplantation, osteochondral autografts, or periosteal grafts. Osteochondral defects <3 cm in diameter and 1 cm in bone depth can be treated with autologous chondrocyte transplantation, osteochondral autografts, or periosteal grafts. Articular defects >3 cm in diameter and 1 cm in bone depth require osteochondral allografts. This is a rough guide to treatment and only the opinion of the author. The greater the bone involvement and the less contained the defect, the greater the need for allograft tissue. Allograft tissue should, however, only be used when the size of the lesion is beyond the other techniques. For all of these techniques, realignment osteotomy should be performed as an adjunct procedure if the lesion is in a compartment under more than physiological compression.     

Skeletal Stem/Progenitor Cells in Periosteum and Skeletal Muscle Share a Common Molecular Response to Bone Injury

Bone regeneration involves skeletal stem/progenitor cells (SSPCs) recruited from bone marrow, periosteum, and adjacent skeletal muscle. To achieve bone reconstitution after injury, a coordinated cellular and molecular response is required from these cell populations. Here, we show that SSPCs from periosteum and skeletal muscle are enriched in osteochondral progenitors, and more efficiently contribute to endochondral ossification during fracture repair as compared to bone-marrow stromal cells. Single-cell RNA sequencing (RNAseq) analyses of periosteal cells reveal the cellular heterogeneity of periosteum at steady state and in response to bone fracture. Upon fracture, both periosteal and skeletal muscle SSPCs transition from a stem/progenitor to a fibrogenic state prior to chondrogenesis. This common activation pattern in periosteum and skeletal muscle SSPCs is mediated by bone morphogenetic protein (BMP) signaling. Functionally, Bmpr1a gene inactivation in platelet-derived growth factor receptor alpha (Pdgfra)-derived SSPCs impairs bone healing and decreases SSPC proliferation, migration, and osteochondral differentiation. These results uncover a coordinated molecular program driving SSPC activation in periosteum and skeletal muscle toward endochondral ossification during bone regeneration. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Osteochondral allograft transplantation in the knee

Fresh osteochondral allograft (OCA) transplantation has over a 100-year clinical history. Many clinical and basic scientific studies have been performed with the result that allografting is now a part of the "cartilage repair paradigm" for the treatment of chondral or osteochondral lesions. In the knee joint, allografting has also been successfully used in complex joint reconstruction for the treatment of osteonecrosis, fracture malunion, and selected cases of osteoarthritis. Unlike many other cartilage repair techniques, OCA have the ability to restore mature, hyaline articular cartilage to the affected area. By virtue of their composite structure (cartilage and bone), allografts also can restore diseased or damaged bone often present in large or complex lesions. Nevertheless, OCA present unique and important difficulties in their clinical application, such as allograft tissue availability, safety issues, and immunologic response to the graft. Ongoing investigations continue to clarify the indications, surgical techniques, and clinical outcomes of fresh OCA.     

Partielle und komplette Gelenktransplantation mit frischen osteochondralen Allografts – das FLOCSAT-Konzept

Cartilage defects in adult patients do not heal well. Fresh osteochondral allograft (OCA) transplantation is based on mature, living, mechanically sound hyaline cartilage attached to a bone interface, which is brought into an osteochondral defect, where it becomes osseointegrated. According to current knowledge, intact hyaline cartilage tissue is immune privileged and does not, in contrast to bone, meniscus or ligaments, cause an immune reaction. The technique has the unique advantage of transplanting viable, mature and mechanically stable hyaline cartilage into the affected area. An OCA is the only biological surgical technique for chondral and osteochondral lesions after failed cell-based techniques or autologous osteochondral transplantation.Fresh osteochondral allografts with mainly small cylindrical transplants show survival of 20 years and more. Based on this experience the FLOCSAT (fresh large [>?10 cm²] osteochondral shell allograft transplantation) concept with the thinnest possible (<?6–8 mm) bone thickness has been developed. Cells survive in special media at 4 °C for 4 weeks or more and are transplanted with a minimum of 70% living cells in a live/dead assay and cell density >?200 cells/mm².FLOCSATs can replace parts or entire joints as uniplanar or multiplanar(n-planar)-FLOCSAT, as unipolar, bipolar or tripolar(n-polar)-FLOCSAT, and in combination with meniscus and/or ligaments (nMnL)-FLOCSAT (n number of structures).The FLOCSAT concept was applied successfully to knee, ankle and elbow joints. All transplants showed sound osseointegration. Cartilage failure was the reason for unsuccessful outcome. Challenges remain regarding graft availability, precise size matching, complex logistics, demanding surgical technique in complex geometries, and open questions in immunology and chimerism.