Load Distribution After Serial Resection of the Posterior Horn of the Lateral Meniscus and Subsequent Meniscal Allograft Transplant: A Biomechanical Study.

BACKGROUND: Data are lacking as to when a meniscal allograft transplant (MAT) may be biomechanically superior to a partially resected lateral meniscus. HYPOTHESIS: Lateral MAT using a bone bridge technique would restore load distribution and contact pressures in the tibiofemoral joint to levels superior to those of a partial lateral meniscectomy. STUDY DESIGN: Controlled laboratory study. METHODS: Eleven fresh-frozen human cadaveric knees were evaluated in 5 lateral meniscal testing conditions (native, one-third posterior horn meniscectomy, two-thirds posterior horn meniscectomy, total meniscectomy, MAT) at 3 flexion angles (0°, 30°, and 60°) under a 1600-N axial load. Pressure sensors were used to acquire contact pressure, contact area, and peak contact pressure within the tibiofemoral joint. RESULTS: Limited (one-third and two-thirds) partial lateral posterior horn meniscectomy showed no significant increase in mean and peak contact pressures as well as no significant decrease in contact area compared with the intact state. Total meniscectomy significantly increased mean contact pressure at 0° and 30° (P = .008 and P < .001, respectively), increased peak contact pressure at 30° (P = .04), and decreased mean contact area in all flexion angles compared with the native condition (P < .01). Lateral MAT significantly improved mean contact pressure compared with total meniscectomy at 0° and 30° (P = .002 and P = .003, respectively) and increased contact area at 30° and 60° (P = .003 and P = .009, respectively), although contact area was still significantly smaller (24.1%) after MAT relative to the native meniscus (P = 0.015). However, allograft transplant did not result in better tibiofemoral contact biomechanics compared with limited partial meniscectomy (P > .05). CONCLUSION: The peripheral portion of the lateral meniscus provided the most important contribution to the distribution of contact pressure across the tibiofemoral joint in the cadaveric model. Total meniscectomy significantly increased mean and peak contact pressure in the cadaveric model and decreased contact area. Lateral MAT restored contact biomechanics close to normal but was not superior to the partially meniscectomized status. CLINICAL RELEVANCE: Surgeons should attempt to preserve a peripheral rim of the posterior lateral meniscus. Meniscal allograft transplant appears to improve but not normalize mean contact pressure and contact area relative to total lateral meniscectomy.

Etiology of Cartilage Lesions Does Not Affect Clinical Outcomes of Patellofemoral Autologous Chondrocyte Implantation.

OBJECTIVE: To determine the relationship between cartilage lesion etiology and clinical outcomes after second-generation autologous chondrocyte implantation (ACI) in the patellofemoral joint (PFJ) with a minimum of 2 years' follow-up. METHODS: A retrospective review of all patients that underwent ACI in the PFJ by a single surgeon was performed. Seventy-two patients with a mean follow-up of 4.2 ± 2.0 years were enrolled in this study and were stratified into 3 groups based on the etiology of PFJ cartilage lesions: patellar dislocation (group 1; n = 23); nontraumatic lesions, including chondromalacia, osteochondritis dissecans, and degenerative defects (group 2; n = 28); and other posttraumatic lesions besides patellar dislocations (group 3; n = 21). Patient's mean age was 29.6 ± 8.7 years. Patients in group 1 were significantly younger (25.4 ± 7.9 years) than group 2 (31.7 ± 9.6 years; P = 0.025) and group 3 (31.5 ± 6.6 years; P = 0.05). Body mass index averaged 26.2 ± 4.3 kg/m2, with a significant difference between group 1 (24.4 ± 3.2 kg/m2) and group 3 (28.7 ± 4.5 kg/m2; P = 0.005). A clinical comparison was established between groups based on patient-reported outcome measures (PROMs) and failure rates. RESULTS: Neither pre- nor postoperative PROMs differed between groups (P > 0.05). No difference was seen in survivorship between groups (95.7% vs. 82.2% vs. 90.5%, P > 0.05). CONCLUSION: Cartilage lesion etiology did not influence clinical outcome in this retrospective study after second generation ACI in the PFJ. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Femoral Trochlear Geometry in Patients with Trochlear Dysplasia Using MRI Oblique Trochlear View.

The objective of this study was to evaluate trochlear morphology in patients with trochlear dysplasia using a new oblique trochlear magnetic resonance imaging (MRI) view (OTV) in comparison with standard axial MRI sequences. MRI exam of 73 patients with patellofemoral instability (PFI) and the same number of controls were retrospectively reviewed. The oblique trochlear sequence was acquired by inclining the axial plane parallel to the intercondylar roof of the sagittal image, showing the anterior cruciate ligament (ACL) in its entire length. Trochlear morphology was assessed on axial and oblique trochlear sequences at three levels: level 1 at 25%, level 2 at 50%, and level 3 at 75% of the length of the trochlear groove. Trochlear sulcus angle and sulcus depth were measured at these three levels and compared between the new trochlear and standard axial sequences. Trochlear sulcus angle and sulcus depth were statistically different between axial and oblique trochlear views at all three levels (p < 0,05). Additionally, OTV displayed more uniform sulcus angle and depth along the trochlea. The oblique trochlear view on the MRI can more accurately evaluate trochlear morphology and also better characterize trochlear dysplasia in patients with PFI. This is Level III, retrospective comparative study.

Isolated MPTL reconstruction fails to restore lateral patellar stability when compared to MPFL reconstruction.

PURPOSE: To biomechanically evaluate MPTL reconstruction and compare it with two techniques for MPFL reconstruction in regard to changes in patellofemoral contact pressures and restoration of patellar stability. METHODS: This is an experimental laboratory study in eight human cadaveric knees. None had patellofemoral cartilage lesions or trochlear dysplasia as evaluated by conventional radiographs and MRI examinations. The specimens were secured in a testing apparatus, and the quadriceps was tensioned in line with the femoral shaft. Contact pressures were measured using the TekScan sensor at 30°, 60° and 90°. The sensor was placed in the patellofemoral joint through a proximal approach between femoral shaft and quadriceps tendon to not violate the medial and lateral patellofemoral complex. TekScan data were analysed to determine mean contact pressures on the medial and lateral patellar facets. Patellar lateral displacement was evaluated with the knee positioned at 30° of flexion and 9 N of quadriceps load, then a lateral force of 22 N was applied. The same protocol was used for each condition: native, medial patellofemoral complex lesion, medial patellofemoral ligament reconstruction (MPFL-R) using gracilis tendon, MPFL-R using quadriceps tendon transfer, and medial patellotibial ligament reconstruction (MPTL-R) using patellar tendon transfer. RESULTS: No statistical differences were found for mean and peak contact pressures, medial or lateral, among all three techniques. However, while both techniques of MPFL-R were able to restore the medial restraint, MPTL-R failed to restore resistance to lateral patellar translation to the native state (mean lateralization of the patella [mm]: native: 9.4; lesion: 22; gracilis MPFL-R: 8.1; quadriceps MPFL-R: 11.3; MPTL-R: 23.4 (p < 0.001). CONCLUSION: MPTL-R and both techniques for MPFL-R did not increase patellofemoral contact pressures; however, MPTL-R failed to provide a sufficient restraint against lateral patellar translation lateral translation in 30° of flexion. It, therefore, cannot be recommended as an isolated procedure for the treatment of patellar instability.

Macrophage: A Potential Target on Cartilage Regeneration.

Cartilage lesions and osteoarthritis (OA) presents an ever-increasing clinical and socioeconomic burden. Synovial inflammation and articular inflammatory environment are the key factor for chondrocytes apoptosis and hypertrophy, ectopic bone formation and OA progression. To effectively treat OA, it is critical to develop a drug that skews inflammation toward a pro-chondrogenic microenvironment. In this narrative and critical review, we aim to see the potential use of immune cells modulation or cell therapy as therapeutic alternatives to OA patients. Macrophages are immune cells that are present in synovial lining, with different roles depending on their subtypes. These cells can polarize to pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes, being the latter associated with wound-healing by the production of ARG-1 and pro-chondrogenic cytokines, such as IL-10, IL-1RA, and TGF-b. Emerging evidence reveals that macrophage shift can be determined by several stimuli, apart from the conventional in vitro IL-4, IL-13, and IL-10. Evidences show the potential of physical exercise to induce type 2 response, favoring M2 polarization. Moreover, macrophages in contact with oxLDL have effect on the production of anabolic mediators as TGF-b. In the same direction, type II collagen, that plays a critical role in development and maturation process of chondrocytes, can also induce M2 macrophages, increasing TGF-b. The mTOR pathway activation in macrophages was shown to be able to polarize macrophages in vitro, though further studies are required. The possibility to use mesenchymal stem cells (MSCs) in cartilage restoration have a more concrete literature, besides, MSCs also have the capability to induce M2 macrophages. In the other direction, M1 polarized macrophages inhibit the proliferation and viability of MSCs and impair their ability to immunosuppress the environment, preventing cartilage repair. Therefore, even though MSCs therapeutic researches advances, other sources of M2 polarization are attractive issues, and further studies will contribute to the possibility to manipulate this polarization and to use it as a therapeutic approach in OA patients.

Systematic Review of Human Dental Pulp Stem Cells for Cartilage Regeneration.

Background: Symptomatic cartilage lesions and early osteoarthritis produce significant clinical and economic burdens. Cartilage repair can improve the symptoms and delay arthroplasty. The complete healing of damaged cartilage with the consistent reproduction of normal hyaline cartilage has not yet been achieved. The choice of harvesting site might influence the cells' abilities to modulate immunologic and inflammatory responses. Recently, dental pulp has been shown to contain a stem cell niche consisting of dental pulp stem cells (DPSCs) that maintain their self-renewal capacity due to the active environment in the dental pulp of deciduous teeth. Objective: The aim of this study was to critically review the current literature on the potential and limitations of the use of dental pulp-derived mesenchymal stem cells in cell-based therapies for cartilage regeneration. Methods: An electronic, customized search of scientific articles was conducted using the PubMed/MEDLINE and EMBASE databases from their inception to December 2018. The inclusion criteria were applied, and the articles that described the use of DPSC in cartilage treatment were selected for complete evaluation. The articles were classified according to the scaffold used, experimental model, chondrogenic differentiation features, defect location, cartilage evaluation, and results. After the application of the eligibility criteria, a total of nine studies were selected and fully analyzed. Results: A variety of animal models were used, including mice, rats, rabbits, and miniature pigs, to evaluate the quality and safety of human DPSCs in the repair of cartilage defects. Among the articles, two studies focused on preclinical models of cartilage tissue engineering. Five studies implanted DPSCs in other animal sites. Conclusion: The use of DPSCs is a potential new stem cell therapy for articular cartilage repair. The preclinical evidence discussed in this article provides a solid foundation for future clinical trials. Impact statement Osteoarthritis presents an ever-increasing clinical and socioeconomic burden. While cartilage repair has the potential to improve symptoms and delay joint replacement, complete regeneration of hyaline cartilage has been an elusive goal. Dental pulp has been shown to contain a niche that protects dental pulp stem cells (DPSCs) from the cumulative effects of genetic and environmental factors and maintains their self-renewal capacity due to the active environment. Transplantation and preclinical trials have demonstrated the strong potential of regenerative tissue-engineering protocols using DPSCs.

Bone-Plug Versus Soft Tissue Fixation of Medial Meniscal Allograft Transplants: A Biomechanical Study.

BACKGROUND: It is controversial whether soft tissue fixation only and bone-plug techniques for medial meniscal allograft transplantation provide equivalent fixation and restoration of load distribution. Prior studies on this topic did not re-create the clinical situation with use of size-, side-, and compartment-matched meniscal transplants. HYPOTHESIS: Both techniques will provide equivalent fixation of the meniscal transplant and restore load distribution and contact pressures similar to those of the native knee. STUDY DESIGN: Controlled laboratory study. METHODS: Nine fresh-frozen human cadaveric knees underwent mean contact pressure, mean contact area, and peak contact pressure evaluation in 4 medial meniscal testing conditions (native, total meniscectomy, bone-plug fixation, and soft tissue fixation) at 3 flexion angles (0°, 30°, and 60°) using Tekscan sensors under a 700-N axial load. RESULTS: Medial meniscectomy resulted in significantly decreased contact area and increased contact pressure compared with the native condition at all flexion angles (P < .0001). Compared with the native state, soft tissue fixation demonstrated significantly higher mean contact pressure and lower mean contact area at 0° and 30° of flexion (P < .05), while bone-plug fixation showed no significant difference. There was no significant difference in peak contact pressure between study conditions. CONCLUSION: Total medial meniscectomy leads to significantly worsened load distribution within the knee. Medial meniscal allograft transplantation can restore load parameters close to those of the native condition. The bone-plug technique demonstrated improved tibiofemoral contact pressures compared with soft tissue fixation. CLINICAL RELEVANCE: Medial meniscal allograft transplantation with bone-plug fixation is a viable option to restore biomechanics in patients with meniscal deficiency.

Pulse Lavage Fails to Significantly Reduce Bone Marrow Content in Osteochondral Allografts: A Histological and DNA Quantification Study.

BACKGROUND: Current clinical practice calls for pulse lavage of fresh osteochondral allografts (OCAs) to reduce immunogenicity; however, there is limited evidence of its effectiveness in reducing allogenic bone marrow elements. PURPOSE: To evaluate the effectiveness of pulse lavage in removing marrow elements from trabecular bone in fresh OCA transplantation. STUDY DESIGN: Controlled laboratory study. METHODS: The authors evaluated 48 fresh OCA plugs with 4 different common sizes (14- and 24-mm diameter, 6- and 10-mm thickness). Within each size group, half of the samples underwent pulse lavage (n = 6) with saline solution and half were left untreated (no lavage; control group, n = 6). For each treatment and size group, 3 samples were analyzed for DNA content as an indicator of the number of residual nucleated cells; the other 3 samples were histologically analyzed to assess the presence and distribution of cells within subchondral bone pores in 3 specific locations within the plug: peripheral, intermediate, and core. RESULTS: Osteochondral plugs treated with pulse lavage did not show a significant decrease in DNA content in comparison with untreated plugs. Overall, histological analysis did not show a significant difference between the treated and untreated groups (P = .23). Subgroup analysis by size demonstrated decreased marrow content in treated versus untreated groups in the thinner plug sizes (14 × 6 mm and 24 × 6 mm). Histological evaluation by zone demonstrated a significant difference between groups only in the peripheral zone (P = .04). CONCLUSION: Pulse lavage has limited effectiveness in removing marrow elements, in particular in plugs that are larger in diameter and, more importantly, in thickness. Better techniques for subchondral bone treatment are required for more thorough removal of potentially immunogenic marrow elements. CLINICAL RELEVANCE: OCA transplantation has become an established treatment modality. Unfortunately, OCA is not without limitations, chiefly its mode of failure through inadequate integration of the allograft subchondral bone with subsequent collapse. In an effort to improve integration, current clinical practice calls for pulse lavage to remove allogenic bone marrow from the subchondral bone in hopes of decreasing the immunogenicity of the graft and facilitating revascularization.

Anatomic Risk Factors for Focal Cartilage Lesions in the Patella and Trochlea: A Case-Control Study.

BACKGROUND: Focal cartilage lesions in the patellofemoral (PF) joint are common. Several studies correlated PF risk factors with PF instability, anterior knee pain, and PF arthritis; however, there is a lack of evidence correlating those factors to PF focal cartilage lesions. PURPOSE: To evaluate the influence of the anatomic PF risk factors in patients with isolated focal PF cartilage lesions. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Patients with isolated PF focal cartilage lesions were included in the cartilage lesion group, and patients with other pathologies and normal PF cartilage were included in the control group. Multiple PF risk factors were accessed on magnetic resonance imaging scans: patellar morphology (patellar width, patellar thickness, and patellar angle), trochlear morphology (trochlear sulcus angle, lateral condyle index, and trochlear sulcus depth), patellar height (Insall-Salvati ratio and Caton-Deschamps index), axial patellar positioning (patellar tilt, angle of Fulkerson), and quadriceps vector (tibial tuberosity-trochlear groove distance). RESULTS: A total of 135 patients were included in the cartilage lesion group and 100 in the control group. As compared with the control group, the cartilage lesion group had a higher sulcus angle (P = .0007), lower trochlear sulcus depth (P < .0001), lower angle of Fulkerson (P < .0001), lower patellar width (P = .0003), and higher Insall-Salvati ratio (P < .0001). From the patients in the cartilage lesion group, 36% had trochlear dysplasia; 27.6%, patella alta; and 24.7%, abnormal patellar tilt. These parameters were more frequent in the cartilage lesion group (P < .0001). Trochlear lesions were more frequent in men, presented at an older age, and had fewer associated anatomic risk factors. Patellar lesions, conversely, were more frequent in women, presented at younger age, and were more closely associated with anatomic risk factors. CONCLUSION: PF anatomic abnormalities are significantly more common in patients with full-thickness PF cartilage lesions. Trochlear dysplasia, patella alta, and excessive lateral patellar tilt are the most common correlated factors, especially in patellar lesions.

No effect of topical application of tranexamic acid on articular cartilage.

PURPOSE: The objective of this study was to evaluate potential cytotoxicity of TXA on articular cartilage by assessing chondrocyte viability of osteochondral explants after exposure to different concentrations and durations of TXA. METHODS: Thirty-nine osteochondral plugs (OCPs) were harvested from three adult Yucatan minipigs immediately after their death. OCPs were divided into 13 groups exposed to different concentrations of TXA (1, 2 and 4 mg/ml in saline solution) for 1, 3 and 6 h. Negative controls were exposed to saline solution for 0, 1, 3 and 6 h. Chondrocyte viability was assessed by Live/Dead cell assay and calculated as the ratio of live cells (green fluorescence) to overall cells (green + red cells) for each concentration of TXA and time point in a 50-µm scanned image. RESULTS: No correlation was found between chondrocyte viability, and TXA concentration and time of exposure. Overall, chondrocyte viability ranged from 90 to 99%. There was no statistical difference among control group, 1, 2 and 4 mg/ml TXA solutions at each time point [1 h (n.s.), 3 h (n.s.), 6 h (n.s.)]. Similarly, no statistical difference among groups was observed when comparing cell viability at 1, 3 and 6 h of TXA exposure, (Fig. 2) [1 mg/ml (n.s.), 2 mg/ml (n.s.), and 4 mg/ml (n.s.)]. CONCLUSIONS: In conclusion, doses of TXA approximating the current clinical protocols for topical use did not demonstrate any cytotoxic effects on cartilage explants in a Yucatan mini pig model. Thus, supporting the topical application for procedures with intact cartilage, such as partial knee replacement surgery and cartilage repair procedures.

Human Synovial Mesenchymal Stem Cells Good Manufacturing Practices for Articular Cartilage Regeneration.

Background: Cartilage restoration is a desperately needed bridge for patients with symptomatic cartilage lesions. Chondral lesion is a pathology with high prevalence, reaching as much as 63% of general population and 36% among athletes. Despite autologous chondrocyte implantation versatility, it still fails to fully reproduce hyaline articular cartilage characteristics. Mesenchymal stem cells (MSCs) may be isolated from various known tissues, including discarded fragments at arthroscopy such as synovial membrane. Choice of harvesting site is motivated by MSCs' abilities to modulate immunologic and inflammatory response through paracrine communication. Synovial MSCs have a greater proliferation and strong chondrogenic potential than bone and adipose MSCs and a less hypertrophic differentiation than bone MSCs. Good manufacturing practice (GMP) laboratory techniques for human clinical trials are still novel. To our knowledge, there are only two clinical trials in humans published since today. Purpose: Therefore, this work aimed to isolate and characterize synovial MSCs and evaluated their differentiation properties according to GMP standards. Materials and Methods: One-gram tissue sample from three patients of synovia was harvested at the beginning of arthroscopy surgery. MSCs were isolated, expanded, and characterized by flow cytometry. Results: It was possible to isolate and expand MSCs cultures from synovia, characterize MSCs by flow cytometry using proper monoclonal antibodies, and differentiate MSCs by coloring technique after chondrogenic, adipogenic, and osteogenic differentiations. Cartilage treatment may benefit from these tissue engineering protocols since arthroscopic procedures are routinely performed for different purposes in a previous stage and a favorable chondronegic differentiation cell lineage may be collected and stored in a less invasive way. Conclusion: Laboratory protocols established according to presented GMP were able to isolate and characterize MSCs obtained from synovia. Impact Statement Articular cartilage restoration is a desperately needed bridge for patients with symptomatic cartilage lesions and it rises as a socioeconomic issue with a considerable economic burden. Synovial mesenchymal stem cells (MSCs) have a greater proliferation rate and strong chondrogenic potential than bone and adipose MSCs and a less hypertrophic differentiation than bone MSCs. To our knowledge, there are only two human clinical trials with good manufacturing practice laboratory techniques for synovial MSCs harvesting and differentiation. Cartilage treatment may benefit from these tissue engineering protocols since arthroscopic procedures are routinely performed for different purposes in a previous stage.

A New Technique for Distalization of the Tibial Tubercle That Allows Preservation of the Proximal Buttress.

BACKGROUND: Tibial tubercle osteotomy (TTO) is a treatment option for patients with patellofemoral instability and chondrosis. Occasionally, these patients also present with patella alta, and distalization of the tibial tubercle is desirable. Free distal transfer of the tubercle, however, can compromise mechanical stability of the osteotomy construct, leading to loss of fixation. PURPOSE: To evaluate alternative TTO proximal cut geometries to investigate whether these can result in tubercle distalization while preserving the proximal buttress. STUDY DESIGN: Descriptive laboratory study. METHODS: Three variants of TTO cut geometry were evaluated on Sawbones as well as cadaveric knees. The proximal cut of the osteotomy was modified in 2 axes: anterior-posterior (AP) and medial-lateral (ML). Three variations were used: ML neutral/AP neutral, ML 30° proximal/AP neutral, and ML neutral/AP 30° proximal. The medial cut plane was 45° for all specimens. Tibial tubercle position was evaluated before and after osteotomy to calculate anteriorization, medialization, and distalization. RESULTS: Distalization was achieved with all variants. Increasing the inclination angle of the proximal cut in the AP and ML axes resulted in maximum distalization. A proximally directed cut yielded significantly more distalization when performed in the AP axis than in the ML axis (P < .05). Even the standard, neutral cut resulted in 5 mm of distalization. CONCLUSION: Fulkerson osteotomy allows 3-dimensional repositioning of the tibial tubercle and has historically been utilized to achieve anteriorization and medialization. Even the neutral cut of a standard TTO resulted in distalization, which is relevant for patients with preexisting patella baja. Modification of the proximal cut increased distalization of the tubercle while preserving the proximal buttress, a potential benefit for construct stability. CLINICAL RELEVANCE: These results provide a guideline for adjusting the proximal cut geometry in Fulkerson TTO to meet specific patient needs.

Intralesional Osteophyte Regrowth Following Autologous Chondrocyte Implantation after Previous Treatment with Marrow Stimulation Technique.

Objective Bone marrow stimulation surgeries are frequent in the treatment of cartilage lesions. Autologous chondrocyte implantation (ACI) may be performed after failed microfracture surgery. Alterations to subchondral bone as intralesional osteophytes are commonly seen after previous microfracture and removed during ACI. There have been no reports on potential recurrence. Our purpose was to evaluate the incidence of intralesional osteophyte development in 2 cohorts: existing intralesional osteophytes and without intralesional osteophytes at the time of ACI. Study Design We identified 87 patients (157 lesions) with intralesional osteophytes among a cohort of 497 ACI patients. Osteophyte regrowth was analyzed on magnetic resonance imaging and categorized as small or large (less or more than 50% of the cartilage thickness). Twenty patients (24 defects) without intralesional osteophytes at the time of ACI acted as control. Results Osteophyte regrowth was observed in 39.5% of lesions (34.4% of small osteophytes and 5.1% of large osteophytes). In subgroup analyses, regrowth was observed in 45.8% of periosteal-covered defects and in 18.9% of collagen membrane-covered defects. Large osteophyte regrowth occurred in less than 5% in either group. Periosteal defects showed a significantly higher incidence for regrowth of small osteophytes. In the control group, intralesional osteophytes developed in 16.7% of the lesions. Conclusions Even though intralesional osteophytes may regrow after removal during ACI, most of them are small. Small osteophyte regrowth occurs almost twice in periosteum-covered ACI. Large osteophytes occur only in 5% of patients. Intralesional osteophyte formation is not significantly different in preexisting intralesional osteophytes and control groups.