Faculty Bibliography

OBJECTIVE:Biologics are increasingly used for cartilage repair and osteoarthritis (OA) treatment. This study aimed to provide an overview of the clinical trials conducted on this subject. DESIGN:Two-word combinations of two sets of key words "cartilage"; "joint"; "osteoarthritis" and "biologics"; "stem cells"; "cell implantation" were used to search the database of ClinicalTrials.gov and supplemented with searches of PubMed and EMbase. The registered trials were analyzed for clinical conditions, completion status, phases, and investigated biologics. Recently completed trials with posted/published results were summarized. RESULTS:From 2000 to 2022, a total of 365 clinical trials were registered at ClinicalTrials.gov to use biologics for cartilage repair and OA treatment. Since 2006, the number of registered trials accelerated at an annual rate of 16.4%. Of the 265 trials designated with a phase, 72% were early Phase 1, Phase 1, and Phase 2. Chondrocytes and platelet-rich plasma (PRP) were studied in nearly equal number of early- and late-stage trials. Mesenchymal stem/stromal cells (MSCs) were the most commonly investigated biologics (38%) and mostly derived from bone marrow and adipose tissue (70%). In last 5 years, 32 of the 72 completed trials posted/published results, among which seven Phase 3 trials investigated chondrocytes, PRP, bone marrow aspirate concentrate, hyaluronic acid, collagen membrane, and albumin. CONCLUSIONS:There was a rapid increase in the number of registered clinical trials in recent years, using a variety of biologics for cartilage repair and OA treatment. Majority of the biologics still require late-stage trials to validate their clinical effectiveness.

BACKGROUND:An international consensus group of experts was convened to collaboratively advance toward consensus opinions based on the best available evidence on key topics within cartilage repair of the ankle. The purpose of this article is to present the consensus statements on osteochondral lesions of the tibial plafond (OLTP) and on ankle instability with ankle cartilage lesions developed at the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. METHODS:Forty-three experts in cartilage repair of the ankle were convened and participated in a process based on the Delphi method of achieving consensus. Questions and statements were drafted within 4 working groups focusing on specific topics within cartilage repair of the ankle, after which a comprehensive literature review was performed and the available evidence for each statement was graded. Discussion and debate occurred in cases where statements were not agreed on in unanimous fashion within the working groups. A final vote was then held. RESULTS:A total of 11 statements on OLTP reached consensus. Four achieved unanimous support and 7 reached strong consensus (greater than 75% agreement). A total of 8 statements on ankle instability with ankle cartilage lesions reached consensus during the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. One achieved unanimous support, and seven reached strong consensus (greater than 75% agreement). CONCLUSION:These consensus statements may assist clinicians in the management of these difficult clinical pathologies. LEVEL OF EVIDENCE:Level V, mechanism-based reasoning.

BACKGROUND:The evidence supporting best practice guidelines in the field of cartilage repair of the ankle are based on both low quality and low levels of evidence. Therefore, an international consensus group of experts was convened to collaboratively advance toward consensus opinions based on the best available evidence on key topics within cartilage repair of the ankle. The purpose of this article is to report the consensus statements on "Pediatric Ankle Cartilage Lesions" developed at the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. METHODS:Forty-three international experts in cartilage repair of the ankle representing 20 countries convened to participate in a process based on the Delphi method of achieving consensus. Questions and statements were drafted within four working groups focusing on specific topics within cartilage repair of the ankle, after which a comprehensive literature review was performed and the available evidence for each statement was graded. Discussion and debate occurred in cases where statements were not agreed upon in unanimous fashion within the working groups. A final vote was then held, and the strength of consensus was characterised as follows: consensus: 51-74%; strong consensus: 75-99%; unanimous: 100%. RESULTS:A total of 12 statements on paediatric ankle cartilage lesions reached consensus during the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. Five achieved unanimous support, and seven reached strong consensus (>75% agreement). All statements reached at least 84% agreement. CONCLUSIONS:This international consensus derived from leaders in the field will assist clinicians with the management of paediatric ankle cartilage lesions.

BACKGROUND:The evidence supporting best practice guidelines in the field of cartilage repair of the ankle is based on both low quality and low levels of evidence. Therefore, an international consensus group of experts was convened to collaboratively advance toward consensus opinions based on the best available evidence on key topics within cartilage repair of the ankle. The purpose of this article is to report the consensus statements on "terminology for osteochondral lesions of the ankle" developed at the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. METHODS:Forty-three international experts in cartilage repair of the ankle representing 20 countries were convened and participated in a process based on the Delphi method of achieving consensus. Questions and statements were drafted within four working groups focusing on specific topics within cartilage repair of the ankle, after which a comprehensive literature review was performed, and the available evidence for each statement was graded. Discussion and debate occurred in cases where statements were not agreed on in unanimous fashion within the working groups. A final vote was then held, and the strength of consensus was characterised as follows: consensus, 51%-74%; strong consensus, 75%-99%; unanimous, 100%. RESULTS:A total of 11 statements on terminology and classification reached consensus during the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. Definitions are provided for osseous, chondral and osteochondral lesions, as well as bone marrow stimulation and injury chronicity, among others. An osteochondral lesion of the talus can be abbreviated as OLT. CONCLUSIONS:This international consensus derived from leaders in the field will assist clinicians with the appropriate terminology for osteochondral lesions of the ankle.

BACKGROUND:Optimal characterization of Adult acquired flatfoot deformity (AAFD) on two-dimensional radiograph can be challenging. Weightbearing Cone Beam CT (CBCT) may improve characterization of the three-dimensional (3D) structural details of such dynamic deformity. We compared and validated AAFD measurements between weightbearing radiograph and weightbearing CBCT images. METHODS:20 patients (20 feet, right/left: 15/5, male/female: 12/8, mean age: 52.2) with clinical diagnosis of flexible AAFD were prospectively recruited and underwent weightbearing dorsoplantar (DP) and lateral radiograph as well as weightbearing CBCT. Two foot and ankle surgeons performed AAFD measurements at parasagittal and axial planes (lateral and DP radiographs, respectively). Intra- and Inter-observer reliabilities were calculated by Intraclass correlation (ICC) and Cohen's kappa. Mean values of weightbearing radiograph and weightbearing CBCT measurements were also compared. RESULTS:Except for medial-cuneiform-first-metatarsal-angle, adequate intra-observer reliability (range:0.61-0.96) was observed for weightbearing radiographic measurements. Moderate to very good interobserver reliability between weightbearing radiograph and weightbearing CBCT measurements were observed for the following measurements: Naviculocuneiform-angle (ICC:0.47), Medial-cuneiform-first-metatarsal-gapping (ICC:0.58), cuboid-to-floor-distance (ICC:0.68), calcaneal-inclination-angle(ICC:0.7), axial Talonavicular-coverage-angle(ICC:0.56), axial Talus-first-metatarsal-angle(ICC:0.62). Comparing weightbearing radiograph and weightbearing CBCT images, statistically significant differences in the mean values of parasagittal talus-first-metatarsal-angle, medial-cuneiform-first-metatarsal-angle, medial-cuneiform-to-floor-distance and navicular-to-floor-distance was observed (P < 0.05). CONCLUSION/CONCLUSIONS:Moderate to very good correlation was observed between certain weightbearing radiograph and weightbearing CBCT measurements, however, significant difference was observed between a number of AAFD measurements, which suggest that 2D radiographic evaluation could potentially underestimate the severity of AAFD, when compared to 3D weightbearing CT assessment.

Level V, clinical tips.

Foot fat pad (FFP) is a highly functionalized fat depot of great significance for weight bearing in the foot. Mesenchymal stromal cells (MSCs) in subcutaneous adipose tissues are widely studied for regenerative potentials. MSCs in FFP, which may contribute to the physiological and pathological conditions of the foot, have not been characterized. In this study, MSCs were isolated from FFP (designated as MSCs-ffp) and subcutaneous adipose tissue (designated as MSCs-sub) from rats. The cell surface markers, proliferation, and efficiency of colony formation were compared between MSCs-ffp and MSCs-sub. In addition, MSCs-ffp were induced for osteogenic, chondrogenic, and adipogenic differentiation. The tri-lineage differentiation potentials were compared between MSCs-ffp and MSCs-sub by the expression of Runx2, Sox9, and proliferator-activated receptor gamma (PPAR-γ), respectively, using quantitative polymerized chain reaction. The expression of elastin and associated genes by MSCs-ffp were also evaluated. MSCs-ffp, like MSCs-sub, expressed CD44, CD73, and CD90. MSCs-ffp and MSCs-sub proliferated at similar rates but MSCs-ffp formed more colonies than MSCs-sub. MSCs-ffp were capable of differentiating into osteogenic, chondrogenic, and adipogenic lineages. Under the conditions of osteogenic and adipogenic differentiation, MSCs-sub expressed more Runx2 and PPAR-γ, respectively, than MSCs-ffp. The undifferentiated MSCs-ffp upregulated the expression of fibulin-5. In conclusion, MSCs-ffp shared common biology with MSCs-sub but were more efficient in colony formation, less adipogenic and osteogenic, and participated in elastogenesis. The unique features of MSCs-ffp may relate to their roles in the physiological functions of FFP.

BACKGROUND/UNASSIGNED:Surgeons frequently add an Achilles tendon lengthening or gastrocnemius recession to increase dorsiflexion following total ankle replacement. Previous studies have looked at the effects of these procedures on total tibiopedal motion. However, tibiopedal motion includes motion of the midfoot and hindfoot as well as the ankle replacement. The current study examined the effects of Achilles tendon lengthening and gastrocnemius recession on radiographic tibiotalar motion at the level of the prosthesis only. METHODS/UNASSIGNED:Fifty-four patients with an average of 25 months follow-up after total ankle replacement were divided into 3 groups: (1) patients who underwent Achilles tendon lengthening, (2) patients who had a gastrocnemius recession, (3) patients with no lengthening procedure. Tibiotalar range of motion was measured on lateral dorsiflexion-plantarflexion radiographs using reference lines on the surface of the implants. RESULTS/UNASSIGNED:Both Achilles tendon lengthening and gastrocnemius recession significantly increased tibiotalar dorsiflexion when compared to the group without lengthening. However, the total tibiotalar range of motion among the 3 groups was the same. Interestingly, the Achilles tendon lengthening group lost 11.7 degrees of plantarflexion compared to the group without lengthening, which was significant. CONCLUSION/UNASSIGNED:Both Achilles tendon lengthening and gastrocnemius recession increased radiographic tibiotalar dorsiflexion following arthroplasty. Achilles tendon lengthening had the unexpected effect of significantly decreasing plantarflexion. Gastrocnemius recession may be a better choice when faced with a tight ankle replacement because it increases dorsiflexion without a compensatory loss of plantarflexion. LEVEL OF EVIDENCE/UNASSIGNED:Level III, retrospective comparative study.

This study was designed to investigate how low-intensity pulsed ultrasound (LIPUS) suppresses traumatic joint inflammation and thereafter affects the progression of posttraumatic osteoarthritis. Intra-articular fracture (IAF) was created in the right knee of rats. LIPUS was applied to the knees with IAFs for 20 min/d for 2 wk-LIPUS(+) group. The study controls included rats that underwent sham surgery but no LIPUS treatment (control group) or underwent IAF surgery without LIPUS treatment-LIPUS(-) group. By histology, at 4 wk, leukocyte infiltration in the synovium was reduced in the LIPUS(+) group. Furthermore, LIPUS treatment reduced CD68⁺ macrophages in the synovium and limited their distribution mostly in the subintimal synovium. Measured with enzyme-linked immunosorbent assay, interleukin-1β (IL-1β) in the joint fluid of the LIPUS(+) group was reduced to about one-third that in the LIPUS(-) group. By reducing synovial macrophages and lowering IL-1β in the joint fluid, LIPUS is potentially therapeutic for posttraumatic osteoarthritis.