Lars Goebel

Effect of Subchondral Drilling on the Microarchitecture of Subchondral Bone Analysis in a Large Animal Model at 6 Months

Background: Marrow stimulation techniques such as subchondral drilling are clinically important treatment options for symptomatic small cartilage defects. Little is known about whether they induce deleterious changes in the subchondral bone. Hypothesis: Subchondral drilling induces substantial alterations of the microarchitecture of the subchondral bone that persist for a clinically relevant postoperative period in a preclinical large animal model. Study Design: Controlled laboratory study. Methods: Standardized full-thickness chondral defects in the medial femoral condyles of 19 sheep were treated by subchondral drilling. Six months postoperatively, the formation of cysts and intralesional osteophytes was evaluated. A standardized methodology was developed to segment the ovine subchondral unit into reproducible volumes of interest (VOIs). Indices of bone structure were determined by micro–computed tomography (micro-CT). Results: Analysis of the microarchitecture revealed the absence of zonal stratification in the ovine subarticular spongiosa, permitting an unimpeded and simultaneous analysis of the entire subchondral trabecular network. Subchondral drilling led to the formation of subchondral bone cysts (63%) and intralesional osteophytes (26%). Compared with the adjacent unaffected subchondral bone, drilling induced significant alterations in nearly all parameters for the microarchitecture of the subchondral bone plate and the subarticular spongiosa, most importantly in bone volume, bone surface/volume ratio, trabecular thickness, separation, pattern factor, and bone mineral density (BMD) (all P ≤ .01). Conclusion: The data show that the ovine subchondral bone can be reliably evaluated using micro-CT with standardized VOIs. We report that subchondral drilling deteriorates the microarchitecture both of the subchondral bone plate and subarticular spongiosa and decreases BMD. These results suggest that the entire osteochondral unit is altered after drilling for an extended postoperative period. Clinical Relevance: The subchondral bone remains fragile after subchondral drilling for longer durations than previously expected. Further evaluations of structural subchondral bone parameters of patients undergoing marrow stimulation are warranted.

Improved repair of chondral and osteochondral defects in the ovine trochlea compared with the medial condyle

Associations between topographic location and articular cartilage repair in preclinical animal models are unknown. Based on clinical investigations, we hypothesized that lesions in the ovine femoral condyle repair better than in the trochlea. Full‐thickness chondral and osteochondral defects were simultaneously established in the weightbearing area of the medial femoral condyle and the lateral trochlear facet in sheep, with chondral defects subjected to subchondral drilling. After 6 months in vivo, cartilage repair and osteoarthritis development was evaluated by macroscopic, histological, immunohistochemical, and biochemical analyses. Macroscopic and histological articular cartilage repair and type‐II collagen immunoreactivity were better in the femoral trochlea, regardless of the defect type. Location‐independently, osteochondral defects induced more osteoarthritic degeneration of the adjacent cartilage than drilled chondral lesions. DNA and proteoglycan contents of chondral defects were higher in the condyle, reflecting physiological topographical differences. The results indicate that topographic location dictates the structural patterns and biochemical composition of the repair tissue in sheep. These findings suggest that repair of cartilage defects at different anatomical sites of the ovine stifle joint needs to be assessed independently and that the sheep trochlea exhibits cartilage repair patterns reflective of the human medial femoral condyle.

Comprehensive analysis of translational osteochondral repair: Focus on the histological assessment.

Articular cartilage guarantees for an optimal functioning of diarthrodial joints by providing a gliding surface for smooth articulation, weight distribution, and shock absorbing while the subchondral bone plays a crucial role in its biomechanical and nutritive support. Both tissues together form the osteochondral unit. The structural assessment of the osteochondral unit is now considered the key standard procedure for evaluating articular cartilage repair in translational animal models. The aim of this review is to give a detailed overview of the different methods for a comprehensive evaluation of osteochondral repair. The main focus is on the histological assessment as the gold standard, together with immunohistochemistry, and polarized light microscopy. Additionally, standards of macroscopic, non-destructive imaging such as high resolution MRI and micro-CT, biochemical, and molecular biological evaluations are addressed. Potential pitfalls of analysis are outlined. A second focus is to suggest recommendations for osteochondral evaluation.

Early loss of subchondral bone following microfracture is counteracted by bone marrow aspirate in a translational model of osteochondral repair

Microfracture of cartilage defects may induce alterations of the subchondral bone in the mid- and long-term, yet very little is known about their onset. Possibly, these changes may be avoided by an enhanced microfracture technique with additional application of bone marrow aspirate. In this study, full-thickness chondral defects in the knee joints of minipigs were either treated with (1) debridement down to the subchondral bone plate alone, (2) debridement with microfracture, or (3) microfracture with additional application of bone marrow aspirate. At 4 weeks after microfracture, the loss of subchondral bone below the defects largely exceeded the original microfracture holes. Of note, a significant increase of osteoclast density was identified in defects treated with microfracture alone compared with debridement only. Both changes were significantly counteracted by the adjunct treatment with bone marrow. Debridement and microfracture without or with bone marrow were equivalent regarding the early cartilage repair. These data suggest that microfracture induced a substantial early resorption of the subchondral bone and also highlight the potential value of bone marrow aspirate as an adjunct to counteract these alterations. Clinical studies are warranted to further elucidate early events of osteochondral repair and the effect of enhanced microfracture techniques.

Surgical anatomy of medial open-wedge high tibial osteotomy: crucial steps and pitfalls.

Purpose To give an overview of the basic knowledge of the functional surgical anatomy of the proximal lower leg and the popliteal region relevant to medial high tibial osteotomy (HTO) as key anatomical structures in spatial relation to the popliteal region and the proximal tibiofibular joint are usually not directly visible and thus escape a direct inspection.Methods The surgical anatomy of the human proximal lower leg and its relevance for HTO are illustrated with a special emphasis on the individual steps of the operation involving creation of the osteotomy planes and plate fixation.ResultsThe posteriorly located popliteal neurovascular bundle, but also lateral structures such as the peroneal nerve, the head of the fibula and the lateral collateral ligament must be protected from the instruments used for osteotomy. Neither positioning the knee joint in flexion, nor the posterior thin muscle layer of the popliteal muscle offers adequate protection of the popliteal neurovascular bundle when performing the osteotomy. Tactile feedback through a loss-of-resistance when the opposite cortex is perforated is only possible when sawing and drilling is performed in a pounding fashion. Kirschner wires with a proximal thread, therefore, always need to be introduced under fluoroscopic control. Due to anatomy of the tibial head, the tibial slope may increase inadvertently.ConclusionsEnhanced surgical knowledge of anatomical structures that are at a potential risk during the different steps of osteotomy or plate fixation will help to avoid possible injuries.Level of evidenceExpert opinion, Level V.

Biological Reconstruction of the Osteochondral Unit After Failed Focal Resurfacing of a Chondral Defect in the Knee

Focal resurfacing prostheses are advocated as a novel treatment option for chondral and osteochondral defects caused by trauma, osteochondritis dissecans (OCD), spontaneous osteonecrosis (ON) of the knee joint, and localized osteoarthritis (OA) in otherwise stable joints of middle-aged patients. These metallic implants consist of an articular component with a polished cobalt-chrome (CoCr) surface connected to a fixation component that is placed into the subchondral bone. Their suggested role is to serve as an interim procedure for patients who are too young to undergo total knee replacement as a primary treatment or after failed articular cartilage repair. Proposed advantages are reduced postoperative pain levels, improved function and range of movement, and shorter rehabilitation compared with conventional unicondylar or bicondylar arthroplasty. By definition, when these focal resurfacing prostheses are implanted in chondral defects, the integrity of the subchondral bone is compromised, while the subchondral bone plate needs to be removed during implant site preparation, extending any chondral defect into an osteochondral defect. In the event of early prosthesis removal in younger patients, the question arises as to how the relatively large osteochondral defect resulting after implant removal can be treated. Also, implant fixation in the subchondral bone possibly affected by bone diseases such as ON or OCD remains questionable. We report the case of a 46-year-old patient with a painful focal prosthesis that was initially implanted as a treatment of a chondral defect in the medial femoral condyle in 2008. After its removal, the resulting subchondral bone defect was filled with an autologous cancellous bone graft and covered by a type I/III collagen membrane as an attempt of biological reconstruction as a salvage procedure. This report suggests that focal resurfacing prostheses may not be implanted as a treatment of chondral defects in patients who are too young to undergo possible conversion to knee arthroplasty. It also serves to emphasize the importance of validating the science from the peer-reviewed literature when considering the use of a new medical device.

A novel algorithm for a precise analysis of subchondral bone alterations

Subchondral bone alterations are emerging as considerable clinical problems associated with articular cartilage repair. Their analysis exposes a pattern of variable changes, including intra-lesional osteophytes, residual microfracture holes, peri-hole bone resorption, and subchondral bone cysts. A precise distinction between them is becoming increasingly important. Here, we present a tailored algorithm based on continuous data to analyse subchondral bone changes using micro-CT images, allowing for a clear definition of each entity. We evaluated this algorithm using data sets originating from two large animal models of osteochondral repair. Intra-lesional osteophytes were detected in 3 of 10 defects in the minipig and in 4 of 5 defects in the sheep model. Peri-hole bone resorption was found in 22 of 30 microfracture holes in the minipig and in 17 of 30 microfracture holes in the sheep model. Subchondral bone cysts appeared in 1 microfracture hole in the minipig and in 5 microfracture holes in the sheep model (n = 30 holes each). Calculation of inter-rater agreement (90% agreement) and Cohen’s kappa (kappa = 0.874) revealed that the novel algorithm is highly reliable, reproducible, and valid. Comparison analysis with the best existing semi-quantitative evaluation method was also performed, supporting the enhanced precision of this algorithm.

History of Arthroscopy

The development of arthroscopic surgery can be regarded as one of the milestones in orthopedic surgery within the twentieth century, along with joint arthroplasty and the open reduction and internal fixation of fractures.

Sustained spatiotemporal release of TGF-β1 confers enhanced very early chondrogenic differentiation during osteochondral repair in specific topographic patterns

The continuous presence of TGF‐β is critically important to induce effective chondrogenesis. To investigate chondrogenesis in a cartilage defect, we tested the hypothesis that the implantation of TGF‐β1‐releasing scaffolds improves very early cartilage repair in vivo. Spatiotemporal controlled release of TGF‐β1 was achieved from multiblock scaffolds that were implanted in osteochondral defects in the medial femoral condyles of adult minipigs. We observed a sustained presence of TGF‐β1 at 4 wk in vivo, which significantly promoted structural aspects of early overall cartilage repair, especially cellularity, cellular morphology, and safranin O staining intensity. Furthermore, early aggrecan and type II collagen production were both increased in specific topographic patterns in cartilaginous repair tissue. Sustained release of TGF‐β1 also increased cell numbers and proliferation, staining intensities for the stem cell surface marker, CD105, and number of stromal cell‐derived factor‐1 (SDF‐1) ‐positive cells within cartilaginous repair tissue. These data identify a mechanism by which TGF‐β1 modulates early chon‐ drogenesis by primarily increasing the number of progenitor cells arising from the subchondral bone marrow compartment via the SDF‐1/chemokine (CXC motif) receptor 4 pathway, their proliferation, differentiation, and extracellular matrix deposition in specific topographic patterns, highlighting the pivotal role played by TGF‐ β1 during this crucial phase.—Asen, A.‐K., Goebel, L., Rey‐Rico, A., Sohier, J., Zurakowski, D., Cucchiarini, M., Madry, H. Sustained spatiotemporal release of TGF‐β1 confers enhanced very early chondrogenic differentiation during osteochondral repair in specific topographic patterns. FASEB J. 32, 5298–5311 (2018). www.fasebj.org

Reliable landmarks for precise topographical analyses of pathological structural changes of the ovine tibial plateau in 2-D and 3-D subspaces

Selecting identical topographical locations to analyse pathological structural changes of the osteochondral unit in translational models remains difficult. The specific aim of the study was to provide objectively defined reference points on the ovine tibial plateau based on 2-D sections of micro-CT images useful for reproducible sample harvesting and as standardized landmarks for landmark-based 3-D image registration. We propose 5 reference points, 11 reference lines and 12 subregions that are detectable macroscopically and on 2-D micro-CT sections. Their value was confirmed applying landmark-based rigid and affine 3-D registration methods. Intra- and interobserver comparison showed high reliabilities, and constant positions (standard errors < 1%). Spatial patterns of the thicknesses of the articular cartilage and subchondral bone plate were revealed by measurements in 96 individual points of the tibial plateau. As a case study, pathological phenomena 6 months following OA induction in vivo such as osteophytes and areas of OA development were mapped to the individual subregions. These new reference points and subregions are directly identifiable on tibial plateau specimens or macroscopic images, enabling a precise topographical location of pathological structural changes of the osteochondral unit in both 2-D and 3-D subspaces in a region-appropriate fashion relevant for translational investigations.