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:Achilles tendinopathy is a common cause of posterior ankle and heel pain in both active and sedentary patients. Though the majority of patients respond to first-line non-operative management including activity modification, immobilization, orthotics, and physical therapy with stretching and eccentric strengthening, there is no consensus for patients who fail these treatments. We evaluate the role of iliac crest bone marrow aspirate (BMA) injections as a treatment option for recalcitrant cases. METHODS:A retrospective chart review was conducted of patients with refractory Achilles tendinopathy treated with iliac crest BMA concentrate injection. Symptoms were assessed using the numeric rating system (NRS) pain score at the pre-operative visit and at six, 12, 24, and 48 weeks postoperatively. Post-operative complications were recorded. RESULTS:(range, 18.4 to 34.4), and average duration of symptoms prior to BMA injection was 2.3 years (range, 1 to 7). Pre-operatively, average NRS was 6.26 (95% CI, 5.04 to 7.49), with significant improvement at six weeks (mean, 4.26; 95% CI, 2.94 to 5.59; p = 0.04), ten weeks (mean, 4.13; 95% CI, 2.91 to 5.35; p = 0.012), 24 weeks (mean, 3.40; 95% CI, 2.05 to 4.75; p = 0.03), and 48 weeks (mean, 2.60; 95% CI, 1.14 to 4.06; p = 0.007) post-operatively. Overall, there was trending improvement over the 48-week follow-up period, with a mean improvement in NRS of - 3.22 (95% CI, - 1.06 to - 5.38; p = 0.007) at final follow-up. There was no discernable difference between insertional and non-insertional tendinopathy, and there were no incidences of post-operative complications. CONCLUSION/CONCLUSIONS:Iliac crest BMA appears to be a safe, effective, and potentially lasting treatment option for patients with intractable, insertional and non-insertional Achilles tendinopathy. Patients demonstrated and maintained statistically significant decrease in NRS pain score post-operatively with no complications at the donor or injection site.

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.

Level V, clinical tips.

BACKGROUND:Correction of hammertoe deformities at the proximal interphalangeal (PIP) joint results in an inherent loss of motion that can be a concern for active patients who want to maintain toe function and grip strength. Diaphyseal proximal phalangeal shortening osteotomy (DPPSO) is a joint-sparing procedure resecting a cylindrical portion of the proximal phalanx on the middiaphysis. PATIENTS/METHODS/METHODS:This was a retrospective review including patients treated using DPPSO with at least a 1-year follow-up. Demographic, comorbidity, and Visual Analogue Scale (VAS) scores and complication data were obtained. Radiological assessment included union status and alignment. Medial frontal anatomical (mFAA), frontal proximal interphalangeal (mFIA), plantar lateral anatomical (pLAA), and medial and plantar lateral interphalangeal angles (pLIA) were measured. RESULTS:< .01). Union occurred in all patients at an average of 11.2 weeks. Complications were present on 4 toes (8.8%), with no recurrences. The pLIA significantly changed from 44.9° to 17.9°. There were no significant differences in the preoperative and postoperative values of the mFAA, pLAA, and mFIA. CONCLUSIONS:DPPSO provides adequate pain relief and corrects the PIP joint in the lateral plane without significantly affecting the coronal plane or the anatomical axis of the phalanx in the frontal and lateral views, nor producing secondary deformities. DPPSO is a safe, effective, and reproducible technique with a low complication rate. LEVELS OF EVIDENCE/UNASSIGNED:

BACKGROUND/UNASSIGNED:We investigated the long-term radiographic outcomes of the Cotton osteotomy performed at our institution by the 2 senior authors in conjunction with other reconstruction procedures to correct adult-acquired flatfoot deformity (AAFD). METHODS/UNASSIGNED:We retrospectively studied patients who underwent Cotton osteotomy between 2005 and 2010 with minimum 4-year follow-up. Radiographic assessment was made on weightbearing radiographs taken at 4 different time intervals: preoperative, early (first postoperative full weightbearing), intermediate (between 1 and 4 years postoperatively), and final (over 4 years postoperatively). RESULTS/UNASSIGNED:= .35) between early radiographs and final follow-up. DISCUSSION/UNASSIGNED:This is the longest reported radiographic follow-up of the Cotton osteotomy performed to address forefoot varus deformity as part of AAFD. The Cotton osteotomy achieved radiographic correction of the medial longitudinal arch at early follow-up, but approximately half of the patients had lost over 50% of that correction at final follow-up. The lengthened angular shape of the cuneiform did not collapse, implying that further collapse occurred through the medial column joints. LEVEL OF EVIDENCE/UNASSIGNED:Level IV, case series.

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.

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.