Hongsen Chiang

Evaluation of articular cartilage repair using biodegradable nanofibrous scaffolds in a swine model: a pilot study

The aim of this study was to evaluate a cell‐seeded nanofibrous scaffold for cartilage repair in vivo. We used a biodegradable poly(ε‐caprolactone) (PCL) nanofibrous scaffold seeded with allogeneic chondrocytes or xenogeneic human mesenchymal stem cells (MSCs), or acellular PCL scaffolds, with no implant as a control to repair iatrogenic, 7 mm full‐thickness cartilage defects in a swine model. Six months after implantation, MSC‐seeded constructs showed the most complete repair in the defects compared to other groups. Macroscopically, the MSC‐seeded constructs regenerated hyaline cartilage‐like tissue and restored a smooth cartilage surface, while the chondrocyte‐seeded constructs produced mostly fibrocartilage‐like tissue with a discontinuous superficial cartilage contour. Incomplete repair containing fibrocartilage or fibrous tissue was found in the acellular constructs and the no‐implant control group. Quantitative histological evaluation showed overall higher scores for the chondrocyte‐ and MSC‐seeded constructs than the acellular construct and the no‐implant groups. Mechanical testing showed the highest equilibrium compressive stress of 1.5 MPa in the regenerated cartilage produced by the MSC‐seeded constructs, compared to 1.2 MPa in the chondrocyte‐seeded constructs, 1.0 MPa in the acellular constructs and 0.2 MPa in the no‐implant group. No evidence of immune reaction to the allogeneically‐ and xenogeneically‐derived regenerated cartilage was observed, possibly related to the immunosuppressive activities of MSCs, suggesting the feasibility of allogeneic or xenogeneic transplantation of MSCs for cell‐based therapy. Taken together, our results showed that biodegradable nanofibrous scaffolds seeded with MSCs effectively repair cartilage defects in vivo, and that the current approach is promising for cartilage repair. Copyright

Multipotential mesenchymal stem cells from femoral bone marrow near the site of osteonecrosis.

Stem cell‐based therapies for degenerative disorders and injuries are promising in the new era. Multipotential mesenchymal stem cells (MSCs) from bone marrow (BM) are on the leading edge because they are easy to expand in culture while maintaining their multilineage potential. In vitro assessment of the chondrogenic and osteogenic potentials of cultured MSCs has been established, and the BM used in those experiments was exclusively from healthy donors via iliac crest aspiration. It is unknown whether human marrow obtained from femurs also contains these multipotential MSCs. We collected marrow from proximal femurs of two patients undergoing total hip replacement surgery for femoral head osteonecrosis and isolated and culture expanded MSCs to about 20 population doublings. These cells were homogeneously positive for β1‐integrin. When pelleted into aggregates and cultured in a medium containing transforming growth factor‐β3 for 14 days, the cells began to express mRNA for aggrecan and collagen type II and to deposit immunoreactive collagen type II and sulfated proteoglycans in the matrix, hallmarks of chondrogenic differentiation. These MSCs could also be differentiated into osteocytic lineage in vitro, as shown by increased expression of alkaline phosphatase activity and deposition of mineral content onto culture plates. These results indicate that femoral BM obtained during hip surgeries also contained multipotential MSCs. These data imply that direct replacement therapy using MSCs from in situ marrow may be possible in the future and that an MSC bank may be established by using marrow from this approach, bypassing the necessity for iliac marrow aspiration from healthy donors.

Repair of Articular Cartilage Defects: Review and Perspectives

Articular cartilage defects heal poorly and lead to catastrophic degenerative arthritis. Clinical experience has indicated that no existing medication substantially promotes the healing process and the cartilage defect requires surgical replacement, preferably with an autograft. However, there is a shortage of articular cartilage that can be donated for autografting. A review of previous unsuccessful experiences reveals the reason for the current strategy to graft cartilage defects with regenerated cartilage. Autologous cartilage regeneration is a cell-based therapy in which autogenous chondrocytes or other chondrogenic cells are cultured to constitute cartilaginous tissue according to the principles of tissue engineering. Current studies are concentrating on improving such techniques from the three elements of tissue engineering, namely the cells, biomaterial scaffolds, and culture conditions. Some models of articular cartilage regeneration have yielded good repair of cartilage defects, in animal models and clinical settings, but the overall results suggest that there is room for improvement of this technique before its routine clinical application. Autologous cartilage regeneration remains the mainstay for repairing articular cartilage defects but more studies are required to optimize the efficacy of regeneration. A more abundant supply of more stable cells, i.e. capable of maintaining the phenotype of chondrogenesis, has to be identified. Porous scaffolds of biocompatible, biodegradable materials that maintain and support the presentation of the chondrogenic cells need to be fabricated. If the cells are not implanted early to allow their in vivo constitution of cartilage, a suitable in vitro cultivation method has to be devised for a consistent yield of regenerative cartilage.

Immediate Effect and Predictors of Effectiveness of Taping for Patellofemoral Pain Syndrome a Prospective Cohort Study

Background: Taping has been used to treat patellofemoral pain syndrome for more than 20 years, but its effectiveness is still controversial. Purpose: This study was undertaken to investigate the effect and predictors of effectiveness of taping in the treatment of patellofemoral pain syndrome. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 118 consecutive patients with patellofemoral pain syndrome were recruited; 100 of them completed this study. Patient sex, age, body mass index, Q angle, lateral patellar displacement, and lateral patellofemoral angle were recorded/measured. One therapist applied adhesive tape to each patient by the McConnell method. Patients scored their pain level on a 100-mm visual analog scale during stepping down from an 8-in platform, before and after taping. The change of score was evaluated by paired t test. Patients with a visual analog scale score decrease of 20 mm or more after taping were considered responsive, and the others were considered nonresponsive. The influences of the aforementioned factors, plus pretaping visual analog scale score, on the effectiveness of taping were analyzed by multivariate logistic regression. Results: The overall mean visual analog scale score decreased significantly after taping (from 49.0 to 29.3 mm; P < .001). There were 66 patients in the responsive group and 34 in nonresponsive group. Among the factors, body mass index, lateral patellofemoral angle, and Q angle were significant predictors of effectiveness. The responsive group had significantly smaller mean lateral patellofemoral angle, larger mean Q angle, and larger mean pretaping visual analog scale score than the nonresponsive group. Conclusion: Taping was an effective treatment for patellofemoral pain syndrome, but was less effective in patients with higher body mass index, larger lateral patellofemoral angle, and smaller Q angle.

Bending strength and holding power of tibial locking screws

The bending strength and holding power of two types of specially designed tibial locking devices, a both-ends-threaded screw and an unthreaded bolt, were studied and compared with four types of commercially available tibial interlocking screws: Synthes, Howmedica, Richards, and Osteo AG. To test bending strength, the devices were inserted into a high molecular weight polyethylene tube and loaded at their midpoint by a materials testing machine to simulate a three point bending test. Single loading yielding strength and cyclic loading fatigue life were measured. To test holding power, the devices were inserted into tubes made of polyurethane foam, and their tips were loaded axially to measure pushout strength. The devices were tested with two different densities of foam materials and two different sizes of pilot holes. Insertion torque and stripping torque of the screws were measured first. Pushout tests were performed with each screw inserted with a tightness equal to 60% of its stripping torque. Test results showed that the yielding strength and the fatigue life were related closely to the inner diameter of the screws. The stripping torque predicted the pushout strength more reliably than did the insertion torque. All tested devices showed greater holding power in the foam with the higher density and with the smaller pilot holes. The both-ends-threaded screw had the highest pushout strength and a satisfactory fatigue strength. The unthreaded bolt had the highest fatigue strength but only fair holding power. Clinical studies of the use of these two types of locking devices are worthwhile.

Differences Between Chondrocytes and Bone Marrow-Derived Chondrogenic Cells

Implantation of autologous chondrogenic cells has become the mainstay strategy for repairing articular cartilage defects. Because the availability of autologous chondrocytes is extremely limited, many recent studies have used artificially induced mesenchymal stem cells (iMSCs) as substitutes for chondrocytes. In this study, we analyzed the differences between the iMSCs and chondrocytes, including their molecular biological and mechanical properties. Human bone marrow-derived MSCs were collected and induced to exhibit the chondrogenic phenotype by culturing the pelleted MSCs in a chemically defined culture medium supplemented with transforming growth factor-beta 1. The molecular biological properties of iMSCs and culture-expanded chondrocytes, including their mRNA profiles and surface proteomics, were analyzed using reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry, respectively. The biomechanical properties of iMSCs and native chondrocytes, including their surface topology, adhesion force, and membrane stiffness, were analyzed using atomic force microscopy (AFM). Both iMSCs and chondrocytes presented type II collagen and glycosaminoglycan, whereas only chondrocytes presented type X collagen. Flow cytometric assays showed that the expression of type II collagen and integrin-1 was higher in the chondrocytes than in the iMSCs. AFM revealed that the MSCs, iMSCs, and chondrocytes greatly differed in their shape. The MSCs were spindle shaped and easily distinguishable from the spherical chondrocytes. The iMSCs appeared round and resembled the spherical chondrocytes; however, the iMSCs were flatter with a central hump of condensed mass and a surrounding thin and broad pleat. The mean adhesion force and mean surface stiffness were significantly lower for the iMSCs (4.54 nN and 0.109 N/m, respectively) than for the chondrocytes (6.86 nN and 0.134 N/m, respectively). To conclude, although the iMSCs exhibited the chondrogenic phenotype, they differed from the chondrocytes in their molecular biological and mechanical properties.

Dome-shaped high tibial osteotomy: a long-term follow-up study.

BACKGROUND High tibial osteotomy (HTO) is a well-established treatment for unicompartmental gonarthrosis of the knee, but its durability and complications remain controversial. We previously introduced a novel dome-shaped HTO, and the long-term follow-up results using this technique are analyzed in this study. METHODS We treated 25 varus knees in 22 patients with medial gonarthrosis, using a specially designed calibrated cutting jig along with rigid external fixation and early joint motion postoperatively. A total of 16 patients (19 knees) completed the study protocol and were followed up for 13-16 years (mean, 15 years). RESULTS The surgery attempted to obtain 8 degrees valgus; the actual postoperative alignment averaged 12.4 degrees valgus, which decreased significantly to 7.8 degrees valgus after 5 years. The outcome as assessed by the Hospital for Special Surgery knee score was excellent or good in 18 knees at 5 years postoperatively, and in 13 knees at the final follow-up, showing a significant deterioration with time. Loss of correction with time was not correlated with the postoperative alignment achieved: at 5 years, loss greater than 2 degrees was found in 12 knees, but their mean corrected angle (11.8 degrees valgus) was not significantly different from that of the others (13.3 degrees valgus). Nor was the loss of correction correlated with the knee scores. The mean amount of joint motion after surgery did not change significantly with time: 124 degrees preoperatively and 114 degrees at the final follow-up. The patellar position also did not change from preoperative values during postoperative follow-up: mean Insall-Salvati index was 0.88 before and 0.90 5 years after surgery, neither showing patella baja. CONCLUSION Dome-shaped HTO is a durable time-buying procedure for patients with unicompartmental medial gonarthrosis, and can avoid subsequent development of patella baja that may complicate further prosthetic arthroplasty.

Comparison of articular cartilage repair by autologous chondrocytes with and without in vitro cultivation.

OBJECTIVE autologous chondrocyte implantation usually requires in vitro cell expansion before implantation. We compared the efficacy of cartilage regeneration by in vitro-expanded chondrocytes at high density and freshly harvested chondrocytes at low density. DESIGN surgically created osteochondral defects at weight-bearing surface of femoral condyles of domestic pigs were repaired by biphasic cylindrical porous plugs of DL-poly-lactide-co-glycolide and beta-tricalcium phosphate. Plugs were seeded with autologous chondrocytes in its chondral phase, and press-fit to defects. Seeded cells were (1) in vitro-expanded chondrocytes harvested from stifle joint 3 weeks before implantation and (2) freshly harvested chondrocytes from recipient knee. Seeding densities were 70 x 10(6) and 7 x 10(6) cells/mL, respectively. Cell-free plugs served as control and defects remained untreated as null control. Outcome was examined at 6 months with International Cartilage Repair Society Scale. RESULTS the two experimental groups were repaired by hyaline cartilage with collagen type II and Safranin-O. Tissue in control group was primarily fibrocartilage. No regeneration was found in null control. Experimental groups had higher mean International Cartilage Repair Society scores than control in surface, matrix, and cell distribution, but were comparable with control in cell viability, subchondral bone, and mineralization. No significant difference existed between two experimental groups in any of the six categories. Uni-axial indentation test revealed similar creeping stress-relaxation property as native cartilage on experimental, but not control, specimen. CONCLUSIONS cartilage could regenerate in both experimental models, in comparable quality. Culture of chondrocytes before implantation is not necessary.

Open exchange locked nailing in humeral nonunions after intramedullary nailing.

Humeral nonunions after cannulated intramedullary nailing have been difficult to reconstruct. In the current study, 23 consecutive patients were treated by open exchange locked nailing with bone grafting. There were 16 men and seven women with a mean age of 46.2 years. The nonunions followed humeral locked nailing in eight patients, Seidel nailing in 13, and Küntscher nailing in two. The average nonunion time was 14.7 months. The nonunions, located at the proximal ⅓ in four humeri, middle ⅓ in 15, and distal ⅓ in four, were antegrade nailed in 10 and retrograde nailed in 13. Nineteen had 8-mm nails and four had 7-mm nails. Supplementary wiring was used in 19 patients. The average followup was 21.4 months. With one surgery, all but one patient (96%) achieved osseous union in, on average, 16.3 weeks. One patient with chronic renal dialysis had persistent nonunion and an osteolytic supracondylar fracture. Other complications included one postoperative radial nerve palsy, one brachial artery injury, and one wire infection. At followup, all patients with solid union had excellent or satisfactory recovery of shoulder function. The average postoperative Neer score (90.7) was significantly better than the average preoperative score (68.5). Two patients had losses of elbow motion of 10° and 20°, respectively. This study shows that humeral nonunion after cannulated intramedullary nailing can be treated effectively by open exchange locked nailing with bone grafting. Supplementary wiring can compress the nonunion and facilitate bone healing.

Locked nailing with interfragmentary wiring for humeral nonunions.

OBJECTIVE Locked nailing for humeral nonunions is threatened by residual fracture gap and fracture motion. This article describes the clinical experience of using interfragmentary wiring to solve these problems. METHODS Interfragmentary wiring was used in 21 consecutive humeral nonunions treated with humeral locked nails. The average age of patients was 49.5 years, with an average nonunion duration of 14.4 months. Eighteen patients had previous operations. Nonunions were located at the proximal third in 4, the middle third in 10, and the distal third in 7. Antegrade nailing was used in 11 and retrograde nailing in 10. Sixteen nonunions were nailed with 8-mm nails and five with 7-mm nails. Interfragmentary wiring was applied to either the posterior or the lateral cortex of humeri in a figure-of-eight configuration. Bone grafting was performed in all and average follow-up time was 22 months. RESULTS With a single operation, all patients achieved osseous union in, on average, 18.3 weeks. One patient with segmental nonunion suffered acute renal failure 4 months after operation, but fracture healing was not affected. Wire infection occurred in one patient with preoperative infection at the nail entry site and was treated by implant removal. Other complications including two transient radial nerve palsies and one brachial artery injury did not affect the final outcome. At follow-up, all but four patients had complete recovery of shoulder flexion and abduction. The average postoperative Neer score (91.1 points) was significantly better than the average preoperative score (65.5 points). All but three patients had complete recovery of elbow motion. CONCLUSION Interfragmentary wiring, a safe procedure if properly performed, could effectively decrease the residual fracture gap and fracture motion in locked nailing of humeral nonunions. Further biomechanical studies and prospective, randomized, controlled studies are warranted.