Faculty Bibliography

OBJECTIVES/OBJECTIVE:Circulating mesenchymal stem cells (MSCs) participate in fracture healing and can be used to enhance fracture healing. This study investigated how CD271-selected MSCs travel in circulation and when is the optimal time to apply MSCs intravenously during fracture healing. METHODS:Based on the expression of CD271, MSCs were isolated from human bone marrow and labeled with cypate, a near-infrared fluorochrome. A unilateral closed fracture was created at the femur in immunodeficient mice. The cypate-labeled MSCs were injected into the tail vein of the mice at days 1 and 3 after fracture and were tracked by near-infrared imaging. The mice were euthanized at 3 weeks after fracture. Immunohistochemistry was performed to detect human MSCs at the fracture sites. Migration of CD271-selected MSCs, under the influence of stem cell-derived factor-1, was assessed in vitro. RESULTS:Intravenously injected at day 1, but not day 3, after fracture, CD271-selected MSCs accumulated at the fracture sites significantly and lasted for at least 7 days. All fractures, with or without MSC injections, healed in 3 weeks. Human cells were localized at the fracture sites in mice by immunohistochemistry. CD271-selected MSCs migrated toward the medium contained stem cell-derived factor-1 in vitro. CONCLUSIONS:After intravenous injection, CD271-selected MSCs were recruited to the fracture sites. The stages of fracture healing influenced the homing of culture-expanded MSCs. In mice, an optimal window of intravenous injection of MSCs was around 24 hours after fracture. CLINICAL RELEVANCE/CONCLUSIONS:Intravenous application of MSCs may serve as a practical route to deliver stem cells for the treatment of fracture nonunion and delayed union.

Plantar fat pad (PFP) is a tissue structure that absorbs the initial impact of walking and running and ultimately bears body weight at standing. This study was designed to quantify the histomorphological changes of the PFP in aged rats. The most medial PFP was dissected from the hind feet of young rats (4 months old, n = 6) and aged rats (24 months old, n = 6). Histological structure and cellular senescence of PFP were analyzed stereologically and histomorphometrically. Immunohistochemistry of matrix metalloproteinase 9 (MMP9) was also performed on PFP tissue sections. Compared with young rats, the thickness of epidermis, dermis and septa of the PFP were significantly reduced in the aged rats. The total volume of adipose tissue in the PFP of aged rats was only about 65% of that in the young rats. The microvascular density and the number of fat pad units (FPU), a cluster of adipocytes enclosed by elastin septa, in the PFP were unchanged in the aged rats. In the aged rats, the number of adipocytes per FPU was reduced but the number of simple adipocyte clusters, without surrounding septa, was increased. The shift of the types of adipocyte clusters in the aged PFP was accompanied by degradation of elastin fibers and increased expression of MMP9. In conclusion, the PFP, particularly the elastic septa, degenerates significantly in aged rats and this may contribute to the pathology of PFP-related diseases.

BACKGROUND:Numerous modalities are used today to treat symptomatic osteochondral lesions in the ankle. However, there are ongoing challenges with the treatment of certain lesions, and concerns exist regarding long-term effectiveness. METHODS:The purpose of the study was to collect clinical outcomes of pain and function in retrospectively and prospectively enrolled patients treated with particulated juvenile cartilage for symptomatic osteochondral lesions in the ankle. This study collected outcomes and incidence of reoperations in standard clinic patients. The analysis presented here includes final follow-up to date for 12 males and 11 females representing 24 ankles. Subjects had an average age at surgery of 35.0 years and an average body mass index of 28 ± 5.8. Fourteen ankles had failed at least 1 prior bone marrow stimulation procedure. The average lesion size was 125 ± 75 mm(2), and the average depth was 7 ± 5 mm. In conjunction with the treatment, 9 (38%) ankles had 1 concomitant procedure and 9 (38%) had more than 1 concomitant procedure. Clinical evaluations were performed with an average follow-up of 16.2 months. RESULTS:Average outcome scores at final follow-up were American Orthopaedic Foot & Ankle Society Ankle-Hindfoot Scale 85 ± 18 with 18 (78%) ankles demonstrating good to excellent scores, Short-Form 12 Health Survey (SF12) physical composite score 46 ± 10, SF12 mental health composite score 55 ± 7.1, Foot and Ankle Ability Measure (FAAM) activities of daily living 82 ± 14, FAAM Sports 63 ± 27, and 100-mm visual analog scale for pain 24 ± 25. Outcomes data divided by lesion size demonstrated 92% (12/13) good to excellent results in lesions 10 mm or larger and those smaller than 15 mm. To date, 1 partial graft delamination has been reported at 16 months. CONCLUSIONS:Preliminary data from a challenging clinical population with large, symptomatic osteochondral lesions in the ankle suggest that treatment with particulated juvenile cartilage could improve function and decrease pain. Longer follow-up and additional subjects are needed to evaluate improvement level and ideal patient indications. LEVEL OF EVIDENCE/METHODS:Level IV, case series.

BACKGROUND:Injection for interdigital neuroma (IDN) may not selectively target the common digital nerve. We investigated the anatomical localization and extent of extravasation with injection for IDN. METHODS:Two fellowship-trained foot and ankle surgeons injected radiopaque contrast into the third webspace of 49 cadaveric specimens (29 with 2 mL and 20 with 1 mL). Computed tomography scan of each specimen was obtained. An independent blinded foot and ankle surgeon analyzed the scans. RESULTS:All injections were accurate. Contrast was found in the second (greater than 70%) and fourth (greater than 30%) webspaces in both injection volume groups. No contrast was found within the third metatarsophalangeal joint. Extravasation extent was significantly greater with 2 mL versus 1 mL of solution in the medial to lateral (27.9 [7.8] mm vs 23.7 [6.0] mm; P = .05) and distal to proximal (52.1 [13.7] mm vs 40.4 [16.1] mm; P = .01) planes. No differences were observed in extravasation extent between surgeons. CONCLUSION/CONCLUSIONS:Injection for IDN was accurate, and extravasation extended into adjacent webspaces in a large percentage of specimens with both solution volumes. Lower extent of extravasation with 1 mL of solution did not indicate better selectivity of injection. CLINICAL RELEVANCE/CONCLUSIONS:Steroid injections for interdigital neuroma were accurate for therapeutic purposes but not diagnostic, except potentially for distinguishing webspace pain from joint pain.

BACKGROUND:In patients with Achilles tendinosis, Achilles tendon debridement can be supplemented with flexor hallucis longus tendon transfer. Outcomes have not been studied prospectively in older, sedentary, and overweight patients. METHODS:Fifty-eight consecutive limbs in fifty-six consecutive older, sedentary patients with insertional or midsubstance Achilles tendinosis were enrolled prospectively and underwent the procedure. Ten patients were lost to follow-up, leaving forty-eight limbs in forty-six patients available for evaluation after twenty-four months. RESULTS:The forty-six patients who were included in the study had an average age of 54 ± 10 years with an average body mass index of 33.8 ± 6.8 kg/m². Significant improvement was observed between baseline and twenty-four months in terms of the visual analog scale for overall pain intensity (6.7 ± 2.3 versus 0.8 ± 2.0; p < 0.001), the Short Form-36 physical score (34.3 ± 8.0 versus 49.0 ± 9.3; p < 0.001), the Ankle Osteoarthritis Scale pain (54.4 ± 19.2 versus 1.9 ± 2.7; p < 0.001) and dysfunction (62.6 ± 21.4 versus 11.0 ± 24.2; p < 0.001) subscale scores, and performance of a single-leg heel rise (1.9 ± 3.0 versus 7.3 ± 2.7 cm; p < 0.001). Significant improvement compared with baseline was observed at three or six months except in the single-leg heel rise. Improvements in terms of pain and function occurred over twenty-four months, with the most improvement occurring in the first twelve months. At twenty-four months, maximum gastrocnemius circumference was significantly less in the involved compared with the uninvolved leg (40.2 ± 5.1 versus 41.2 ± 4.8 cm; p < 0.001). The mean passive range of motion of the first metatarsophalangeal joint decreased from 85.1° ± 25.3° preoperatively to 68.1° ± 36.7° (a 20% change) at six months (p = 0.03). Most patients reported no hallux weakness (57%; twenty-six of forty-six patients) and no loss of balance due to hallux weakness (76%; thirty-five of forty-six patients). Postoperative peroneal tendinitis was observed in seven patients. Complications included deep-vein thrombosis (two patients), superficial infection or delayed wound-healing (six), scar pain (four), and early disruption of the reconstruction due to a fall (one). CONCLUSIONS:Surgical debridement of the Achilles tendon with flexor hallucis longus tendon transfer was associated with significant improvement in terms of Achilles tendon function, physical function, and pain intensity in a group of relatively inactive, older, overweight patients. When present, hallux weakness had minimal functional sequelae.

CD271 has been applied to isolate mesenchymal stem cells (MSCs) from bone marrow and other tissues. Umbilical cord blood is a unique resource of stem cells and endothelial progenitor cells. Isolation of MSCs from umbilical cord blood, however, has been inefficient and inconsistent. This study was designed to examine the potential application of CD271 as a marker for the isolation of MSCs from umbilical cord blood. CD271+ cells were isolated from umbilical cord blood and bone marrow using CD271 antibody-conjugated microbeads, and characterized in osteogenic, chondrogenic and adipogenic differentiation. CD271+ cells from umbilical cord blood were slow to proliferate compared with those isolated from bone marrow. While CD271+ cells from bone marrow differentiated into osteogenic, chondrogenic and adipogenic lineages, there were no sound indications of differentiation by CD271+ cells from umbilical cord blood under the same differentiation conditions applied to the CD271+ cells from bone marrow. The study also found that bone marrow CD271+ cells remarkably upregulated the expression of chondrogenic genes under chondrogenic differentiation induction. When implanted into bone defects in mice, CD271+ cells from bone marrow regenerated significant bone, but the counterparts in umbilical cord blood formed little bone in the bone defects. In conclusion, CD271 is an efficient marker for MSC isolation from bone marrow but has failed to isolate MSCs from umbilical cord blood. CD271+ cells in bone marrow are particularly chondrogenic. The property of CD271+ cells is unique but varies from different tissues.

Standard 4-strand repair of Achilles tendon tears is effective, but additional strength may be desirable in patients who are compromised or those with reruptures. Use of a xenograft scaffold has not been investigated biomechanically in Achilles tendon repair. This study compared stiffness, gap formation, and ultimate load to failure with Krackow repair vs Krackow repair augmented with xenograft scaffold in 6 matched pairs of fresh-frozen human lower extremities. The Achilles tendon was transected 4 cm above the calcaneal insertion. Specimens were randomized to receive standard Krackow repair or Krackow repair augmented with a porcine xenograft scaffold. The graft was wrapped around the repaired tendon, sutured to itself with 2-0 FiberWire (Arthrex, Naples, Florida), and attached to the tendon distally and proximally and then medially and laterally. Specimens were loaded for 200 cycles between 5 and 30 N. Load to 5-mm gapping and load to ultimate failure were measured. Xenograft scaffold augmentation of standard Krakow Achilles tendon repair was significantly stronger and stiffer than standard Krackow repair in a biomechanical model immediately after repair (39.0±8.8 vs 24.4±4.6 N/mm; P=.01). The augmented repair group had significantly higher load to ultimate failure than did the Krackow group (862.7±174.0 vs 479.5±65.5 N; P<.01). Biological factors remain to be investigated, but this augmentation method could provide additional strength in patients who are compromised or those with reruptures.

BACKGROUND:It may be possible to avoid malleolar osteotomy for treatment of osteochondral talar lesions with chondrocyte transplantation techniques, where perpendicular approach to the talar surface is not required. We hypothesized that limited anterior distal tibial plafondplasty would allow access to most of the talar surface. We compared talar access with soft tissue exposure versus plafondplasty. METHODS:Two soft tissue exposures (anteromedial and anterolateral) and two limited anterior distal tibial plafondplasties (anteromedial and anterolateral) were used on 12 cadaver lower-extremity specimens. Digital analysis was used to assess the accessible area. RESULTS:Percentage of total talar dome surface area access increased significantly between soft tissue exposure and limited plafondplasty medially (22.3 +/- 6.3% versus 37.9 +/- 4.6%; p < 0.001) and laterally (22.4 +/- 7.7% versus 37.9 +/- 7.7%; p < 0.001). Percentage sagittal plane access also increased significantly between soft tissue exposure and limited plafondplasty medially 54.4 +/- 12.0% versus 81.3 +/- 9.7%; p < 0.001) and laterally (53.3 +/- 14.5% versus 80.9 +/- 12.8%; p < 0.001). Limited exposure to an additional 14.2 +/- 5% of the total talar surface area was possible. The posterior 10.6 +/- 8% was inaccessible. CONCLUSIONS:A soft tissue approach with limited plafondplasty provided adequate exposure for the majority of the medial and lateral talar surface. Only the central posterior 10% of the talus was not accessed by this method. CLINICAL RELEVANCE/CONCLUSIONS:It may be possible to avoid malleolar osteotomy by using limited plafondplasty to access the talar dome for treatment of osteochondral lesions if perpendicular access to the talus is not required.