The five year outcome of a clinical feasibility study using a biphasic construct with minced autologous cartilage to repair osteochondral defects in the knee.

PURPOSE: Autologous minced cartilage has been used to repair cartilage defects. We have developed a biphasic cylindrical osteochondral construct for such use in human knees, and report the five year post-operative outcomes. METHODS: Ten patients with symptomatic osteochondral lesion at femoral condyles were treated by replacing pathological tissue with the osteochondral composites, each consisted a DL-poly-lactide-co-glycolide chondral phase and a DL-poly-lactide-co-glycolide/ß-tricalcium phosphate osseous phase. A flat chamber between the two phases served as a reservoir to house double-minced (mechanical pulverization and enzymatical dissociation) autologous cartilage graft. The osteochondral lesion was drill-fashioned a pit of identical dimensions as the construct. Graft-laden construct was press fit to the pit. Post-operative outcome was evaluated using Knee Injury and Osteoarthritis Outcome Score (KOOS) up to five years. Regenerated tissue was sampled with arthroscopic needle biopsy for histology at one year, and imaged with magnetic resonance at one, three, and five years to evaluate the neocartilage with MOCART chart. Subchondral bone integration was evaluated with computed tomography at three and five years. RESULTS: Nine patients completed the five-year follow-up. Post-operative mean KOOS, except that of the "symptom" subscale, had been significantly higher than pre-operation from one year and maintained to five years. The change of MOCRAT scores of the regenerated cartilage paralleled the change of KOOS. The osseous phase remained mineralized during the five-year period, yet did not fully integrate with the host bone. CONCLUSIONS: This novel construct for chondrocyte implantation yielded promising mid-term outcome. It repaired the osteochondral lesion with hyaline-like cartilage durable for at least five years.

Topical anesthesia for staple removal from surgical wounds on the knee: a prospective, double-blind, randomized trial.

BACKGROUND: Staple removal from surgical wounds is painful. Only a few articles have provided expert opinions using anesthetic cream for such a problem; however, direct application of the anesthetic cream to a wound may cause infection. A safe alternative can be an anesthetic patch without wound contact. MATERIALS AND METHODS: This was a prospective, double-blind, randomized clinical trial. Sixty patients who underwent primary total knee replacement were assigned to an experimental group or control group. One lidocaine patch was applied around the surgical wound for each patient in the experimental group. Alternatively, the adhesive sides of the lidocaine patches were shielded with waterproof films in the control group. A resident peeled off the patch before a single nursing practitioner removed the staples. Pain was assessed with the 10-cm visual analog scale, and a face pain scale-revised was performed. The patients and the nursing practitioner were blind to the management. RESULTS: Mean visual analog scale and face pain scale-revised scores were significantly lower in the experimental group. The mean pain score was significantly lower in the experimental group if the application time was >47 min; for patients with application time of 47 min or shorter, the score was comparable with the mean pain scores of the control group (P = 0.215). CONCLUSIONS: Removal of the metal skin staples after total knee arthroplasty is associated with moderate-to-severe pain. The lidocaine patch applied topically around the surgical wound could effectively reduce the pain during the procedure, without remarkable complications such as systemic adverse effects or wound contamination.

Early neuromechanical outcomes of the triceps surae muscle-tendon after an Achilles' tendon repair.

OBJECTIVES: To compare the neuromechanical and functional characteristics of the legs of athletes who underwent unilateral Achilles' tendon repair and their controls, and to determine any correlation between the characteristics. DESIGN: A case-control and cross-sectional study. SETTING: A university institute. PARTICIPANTS: Male athletes (N=33) were recruited; 23 in the ≥3- and <12-month postsurgical group (median age, 29.8y; age range, 21.9-40.0y) and 10 in the control group (median age, 30.0y; age range, 21.1-39.5y) who had not undergone any surgery. INTERVENTION: Surgical Achilles' tendon repair in the study group. MAIN OUTCOME MEASURES: Bilateral measurements of activation strategy involving the triceps surae and tibialis anterior muscles, mechanical properties of the Achilles' tendon, and explosive performance tests were conducted. RESULTS: Compared with the noninjured legs and the control legs, the repaired legs showed lower normalized rates of electromyographic rise (RER) in the soleus, gastrocnemius medialis, and gastrocnemius lateralis (P ranged between .006 and .001); and less tendon stiffness, greater hysteresis, and less rates of force development (RFD) (P ranged between .006 and <.001). Repaired legs had less ankle dorsiflexion, a shorter 1-leg hopping distance, and lower balance scores (P≤.001). The noninjured legs of the athletes who underwent surgical Achilles' tendon repair had a lower normalized RER (0-50 ms) in the soleus and lateral gastrocnemius when compared with the legs of the healthy controls (P=.011). The neuromechanical outcomes and explosive performances showed correlations with RFD, 1-leg hopping distance, and balance score. CONCLUSIONS: The athletes who underwent unilateral Achilles' tendon repair demonstrated bilateral neuromechanical deficits within the 1-year postsurgical period.

A Patient with Acute Necrotizing Fasciitis after a Total Knee Replacement: A Case Report.

Necrotizing fasciitis is a relatively rare and serious fatal soft-tissue infection that is characterized by a rapidly spreading bacterial infection located in the subcutaneous tissues. We report a 59-year-old man who was diagnosed with acute necrotizing fasciitis, following a primary total knee replacement. He received primary total knee replacement that was uneventful and smooth intraoperatively. An immediate high fever was reported in the next few days, with several complications, confirming a diagnosis of necrotizing fasciitis. The most effective treatment for this disease is a rapid primary diagnosis and surgical debridement. Gold standard treatment includes intravenous therapy, such as antibiotics, surgical debridement, and intensive care. As a result of possible GI complications that triggered necrotizing fasciitis, the patient underwent flap reconstruction. This report's aim is to review the comprehensive treatment, management, and experience of necrotizing fasciitis, highlighting the roles with a multidisciplinary care team for improving the condition of this patient.

Comparison of quadriceps-sparing minimally invasive and medial parapatellar total knee arthroplasty: a 2-year follow-up study.

BACKGROUND/PURPOSE: Quadriceps-sparing minimally invasive total knee arthroplasty (TKA) has been proposed to limit surgical dissection without compromising surgical outcome. We conducted a prospective and randomized study to compare the outcomes of patients who underwent quadriceps-sparing TKA with the outcomes of those who underwent standard medial parapatellar TKA, after a 2-year follow-up period. METHODS: Eighty primary TKA procedures that were to be performed in 60 osteoarthritis patients were randomly assigned to either a quadriceps-sparing (40 knees) or a standard medial parapatellar (40 knees) group. All surgeries were designed to set the prosthesis with a femoral component alignment of 7° valgus and a tibial component alignment that was perpendicular to the tibial shaft. Surgical time and tourniquet time were recorded. Outcome variables included knee function, as defined by a hospital for special surgery knee score; quadriceps muscle strength, which was measured by an isokinetic dynamometer; pain, as indicated on a visual analog scale; prosthetic position, which was measured on plain radiograph; and range of motion. RESULTS: Patients who underwent the 38 quadriceps-sparing and 37 standard TKA procedures completed the 2-year follow-up period without any infection or revision. The mean surgical time and tourniquet time were significantly longer in the quadriceps-sparing group. The mean peak quadriceps muscle strength, hamstring muscle strength, normalized muscle balance (hamstring/quadriceps ratio), pain score, function score, and range of motion were comparable in both groups at 2 months and 2 years. In the quadriceps-sparing group, both the femoral and the tibial components were significantly more varus-deviated from the expected position. CONCLUSIONS: Patients undergoing quadriceps-sparing and standard medial parapatellar TKA had comparable outcomes for quadriceps muscle strength, hamstring-quadriceps balance, and knee function; however, the quadriceps-sparing TKA was more time consuming surgically and resulted in a less accurate prosthesis position.

Prospective Application of Partially Digested Autologous Chondrocyte for Meniscus Tissue Engineering.

BACKGROUND: Meniscus tissue engineering has yet to achieve clinical application because it requires chondrogenic induction and in vitro cell expansion. Contrarily, cartilage engineering from autologous chondrocytes has been successfully applied in one-stage surgery. If the natural chondrogenic potential of meniscus cells can be demonstrated, meniscus tissue engineering would have more value in clinical settings. MATERIALS AND METHODS: In total, 10 menisci and pieces of cartilage were obtained during total knee replacements. The tissues were collected for cell isolation and expansion. Their chondrogenic properties were examined by immunohistofluorescence and gene expression analyses. RESULTS: In native cartilage, immunofluorescence demonstrated the presence of collagen I, aggrecan, and traces of collagen I, whereas comparable staining was seen in the inner and middle meniscus. The presence of collagen I but the absence of collagen II and aggrecan were observed in the outer meniscus. In passage 2, chondrocytes showed the presence of collagen II and aggrecan, and the absence of vimentin. The vimentin and aggrecan staining were comparable in the inner and middle meniscus cells, whereas the outer cells showed only vimentin staining. In the gene expression analyses, the expressions of collagen II and aggrecan in the native chondrocyte and the inner and middle meniscus were higher than those of the cells from the outer meniscus, but they were not different in collagen I. In the passage 2 culture, chondrocytes had a higher expression of collagen II and aggrecan than the meniscus cells. Cells from the inner and middle areas had higher collagen II and aggrecan expression than those from the outer meniscus. CONCLUSION: Without chondrogenic induction, inner and middle meniscus cells possess a chondrogenic phenotype. Specifically, native meniscus cells exhibited more robust chondrogenic potential compared with those of the passage 2 monolayer culture.

The association between coronary artery disease and osteoporosis: a population-based longitudinal study in Taiwan.

PURPOSE: This large population-based study is the first to analyze the association between coronary artery disease (CAD) and osteoporosis (OP) from the National Health Insurance Research Database (NHIRD) in Taiwan to determine if CAD is associated with OP. METHODS: Data from NHIRD, a national, population-based, retrospective, matched cohort study of 23 million patients, were collected to recruit two matched cohorts: with (n = 192,367) and without (n = 192,367) CAD. The Cox model was used to compare the incidence rate ratio and crude hazard ratio (HR) between the two cohorts for osteoporotic fracture and OP. RESULTS: The CAD cohort had a significantly increased risk for vertebral compression fracture, with an adjusted HR of 1.74 (95% CI, 1.60-1.89). The cumulative incidence of OP was also statistically higher in the cohort versus without CAD (11.6% vs. 5.6%; p ≤ 0.0001, log-rank) during the 10-year follow-up period. The Cox model showed a 2.04-fold increase in the incidence of OP in the CAD cohort, with an adjusted HR of 2.04 (95% confidence interval [CI], 1.99-2.08). CONCLUSIONS: A positive association exists between CAD and development of subsequent osteoporotic fracture and OP. Patients with CAD have a significantly increased risk of developing vertebral compression fracture and a higher incident rate ratio of OP. TRIAL REGISTRATION: IRB approval number: No. C108094 on February 19, 2020.

The Association between Osteoporosis and Peripheral Artery Disease: A Population-Based Longitudinal Follow-Up Study in Taiwan.

Background: There are several possible links that have been used to claim that osteoporosis and peripheral artery disease (PAD) are associated; however, the solid evidence is not sufficient. This study aimed to use the Taiwan National Health Insurance Research Database (NHIRD) to determine if osteoporosis is associated with peripheral artery disease (PAD). Method: NHIRD records from 23 million patients were collected to recruit two matched cohort groups: 64,562 patients with and 64,562 patients without osteoporosis. To compare the crude hazard ratio (HR) and the incidence rate ratio between the two cohort groups for PAD, the Cox model was used. Result: With an adjusted HR of 1.18 (95% CI, 1.08-1.29), the osteoporosis cohort group had a significantly greater risk for PAD than the group without osteoporosis. The cumulative incidence of PAD in the cohort group was also statistically higher than it was in the group without osteoporosis (1.71% and 1.39%; p ≤ 0.0001, log-rank) over the 10-year follow-up period. In addition, the osteoporotic patients with ischemic stroke, chronic obstructive pulmonary disease (COPD), and congestive heart failure (CHF) had a significantly increased risk of PAD based on subgroup analysis. Conclusions: There was a positive association between osteoporosis and the development of PAD, as patients with osteoporosis had an increased incidence of PAD over time.

Relationship of idiopathic osteonecrosis of the femoral head to perfusion changes in the proximal femur by dynamic contrast-enhanced MRI.

OBJECTIVE: The purpose of this article is to relate intramedullary perfusion of the proximal femur to severity of osteonecrosis of the femoral head by using dynamic contrast-enhanced MRI (DCE-MRI). SUBJECTS AND METHODS: Twelve patients (14 symptomatic hips) who underwent DCE-MRI and had subsequent core decompression of the femoral head were examined. Hips were graded for severity according to MRI findings and were assigned scores of 0 (negative findings), 1 (focal marrow abnormalities), and 2 (subchondral collapse). Thirteen asymptomatic hips acted as controls. The DCE-MRI data were analyzed by use of a pharmacokinetic two-compartment model. RESULTS: Compared with control hips, there was significantly greater peak enhancement in the femoral head in hips of all grades (p < 0.001) and in the femoral neck (p = 0.001) and intertrochanteric area (p = 0.001) in grade 2 hips. The time to peak was significantly delayed in the femoral head in grade 0 hips (p = 0.02) and in the intertrochanteric area in grade 2 hips (p = 0.003) compared with the controls. CONCLUSION: As evaluated by DCE-MRI, intramedullary peak enhancement in the femoral head increased with progression of idiopathic osteonecrosis of the femoral head, whereas there was delayed peak enhancement in the femoral head in hips with negative findings and intertrochanteric stasis in advanced osteonecrosis of the femoral head. Such perfusion changes as shown on MRI can occur with early osteonecrosis in the absence of other MRI abnormalities.

Risk factors for hip fracture sites and mortality in older adults.

BACKGROUND: Our study was designed to (1) investigate the risk factors associated with cervical or trochanteric hip fractures; and (2) identify the risk factors for increased mortality in the elderly population sustaining hip fractures, after adjusting the miscellaneous baseline prefracture conditions. METHODS: Two hundred seventeen elder patients with first-time, low-trauma hip fractures were enrolled. The follow-up time ranged from 35 months to 56 months. Potential risk factors for hip fracture types included (1) the 77 items on the self-reported questionnaire; (2) the body height, weight, and body mass index; (3) tests of coordination, handgrip strength, and peak expiratory flow rate; and (4) the bone mineral density variables. GTFN ratio was defined as the bone mineral density ratio between the greater trochanter and the femoral neck. Multivariate logistic regression and Cox regression models were used for analysis. The population attributable risk proportion of death to each significant factor was estimated. RESULTS: Risk factors for trochanteric fractures include a GTFN ratio ≤0.81, being male, and an age >80 years. Risk factors for higher mortality after hip fracture included trochanteric fracture, body mass index ≤20 (kg/m), poor self-assessed health status, peak expiratory flow rate ≤215 (L/min), being male, illiteracy, and coordination abnormality, in the declining order of population attributable risk proportion. Trochanteric fractures had a significantly higher cumulative mortality at 36 months, 48 months, and 60 months than cervical fractures. CONCLUSIONS: The novel GTFN ratio was associated with hip fracture sites. Clinically, cervical and trochanteric fractures represent different disease entities because of the difference in their mortality rates.

Collagenase treatment of cartilaginous matrix promotes fusion of adjacent cartilage.

In articular cartilage-repair, grafts usually fuse unsatisfactorily with surrounding host cartilage. Enzymatic dissociation of cartilaginous matrix to free chondrocytes may benefit fusion. We tested such a hypothesis with human cartilage in vitro, and with porcine cartilage in vivo. Human articular cartilage was collected from knee surgeries, cut into disc-and-ring sets, and randomly distributed into three groups: disc-and-ring sets in Group 1 were left untreated; in Group 2 only discs, and in Group 3 both discs and rings were treated with enzyme. Each disc-and-ring reassembly was cultured in a perfusion system for 14 days; expression of cartilage marker proteins and genes was evaluated by immunohistochemistry and PCR. Porcine articular cartilage from knees was similarly fashioned into disc-and-ring combinations. Specimens were randomly distributed into a control group without further treatment, and an experimental group with both disc and ring treated with enzyme. Each disc-and-ring reassembly was transplanted into subcutaneous space of a nude mouse for 30 days, and retrieved to examine disc-ring interface. In in vitro study with human cartilage, a visible gap remained at disc-ring interfaces in Group 1, yet became indiscernible in Group 2 and 3. Marker genes, including type II collagen, aggrecan and Sox 9, were well expressed by chondrocytes in all specimens, indicating that chondrocytes' phenotype retained regardless of enzymatic treatment. Similar results were found inin vivo study with porcine cartilage. Enzymatic dissociation of cartilaginous matrix promotes fusion of adjacent cartilage. The clinical relevance may be a novel method to facilitate integration of repaired cartilage in joints.

Analysis of the following Related Surgeries of Unicompartmental Knee Arthroplasty and Total Knee Arthroplasty: A Taiwanese National Health Insurance Research Database Population-Based Study.

BACKGROUND: Current treatment options for both unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA) are still controversial with no consistent results in which one is superior to others. This is the first study to examine and analyze the following related data available in patients receiving either UKA or TKA from the National Health Research Database (NHIRD) in Taiwan. METHODS: The database was searched from NHIRD, pooling one million random patients. Patients' age, gender, and comorbidities were analyzed in either UKA or TKA between January 2005 and December 2013, or up until death. For the patients that had received bilateral surgeries, further subgrouping was divided into TKA to TKA, UKA to UKA, TKA to UKA, and UKA to TKA to analyze the completion rate curve. Additional analysis of the order codes 64202B, 64053B, and 64198B was defined as failures, and the related failure rate curves were analyzed separately within ten years. Finally, infection-related codes were analyzed. RESULTS: 6,179 patients (n = 276 UKA; n = 5903 TKA) were selected. Age (p < 0.0001) and gender (p = 0.037) had significant differences, with more young population and males having UKA than TKA. Most comorbidities had no significant difference. For the bilateral surgery analysis, the UKA to UKA group had the fastest completion rate (p < 0.001) and UKA to TKA was the slowest. There were no significant differences in the failure rates of 64202B, 64053B, and 64198B. CONCLUSION: Most UKA and TKA are appropriate solutions to treat patients with osteoarthritis or osteonecrosis. UKA to UKA is the quickest bilateral completion surgery, and UKA has a higher chance of undergoing revision surgery than TKA.

Sulfation pattern of chondroitin sulfate in human osteoarthritis cartilages reveals a lower level of chondroitin-4-sulfate.

Chondroitin sulfates (CS) account for more than 80% of the glycosaminoglycans of articular cartilage, which impart its physiological functions. We quantified the absolute concentration of the CS components of the full thickness cartilages from the knees of patients with terminal-phase osteoarthritis. Osteochondrol biopsies were removed from the medial femoral condyle and lateral femoral condyle of sixty female patients received total knee arthroplasty, aged from 58 to 83 years old. We found the total CS concentrations and chondroitin-4-sulfate disaccharide were significantly lowered in osteoarthritic samples. Microstructure analysis indicated while chondroitin-0-sulfate was equally distributed across different zones of the osteoarthritic cartilages, chondroitin-4-sulfate is significantly less in the deep zones. Down-regulation of sulfotransferases, the enzymes responsible for CS sulfation, in the lesion site of cartilage were observed. Our study suggested chondroitin-4-sulfate down-regulation can be a diagnostic marker for degraded osteoarthritis cartilage, with potential implications in cartilage regeneration.

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.

Quadriceps-sparing, minimal-incision total knee arthroplasty: a comparative study.

Our study was conducted to compare radiographic alignments and functional outcomes with 2 approaches to minimal-incision total knee arthroplasty (TKA): the minimal-incision medial parapatellar (MP) approach and the quadriceps-sparing (QS) approach with side-cutting instruments. Sixty patients (80 knees) with primary osteoarthritis were randomly assigned to receive MP or QS TKA. Postoperative alignment of the femoral component was significantly less valgus, and postoperative alignment of the tibial component was significantly more varus with the QS approach than with the MP approach. One tibial outlier and 3 femoral outliers were observed with QS TKA. The overall postoperative hip-knee-ankle axis was more varus, and surgical time was longer with QS TKA. Short-term isokinetic peak muscle torque, postoperative pain, and functional outcomes did not differ between the approaches.

The effect of posterior capsule repair upon post-operative hip dislocation following primary total hip arthroplasty.

BACKGROUND: Herein, we evaluated, retrospectively, the effect of posterior capsular repair upon postoperative hip dislocation subsequent to total hip arthroplasty (THA) incorporating a posterolateral approach. METHODS: A total of 181 patients undergoing 204 primary non-complicated THA surgical procedures in the period from January 2000 to October 2005 inclusively were included in this study. The patients were separated into two groups by whether the posterior capsular repair had been incorporated in the surgical procedure. For the surgeon did not commence repairing the posterior capsule until July, 2003, all members in the group that did not undergo posterior capsular repair (142 hips from 131 patients) were collected since January, 2000 to July, 2003, while the members in the group that underwent posterior capsular repair (62 hips from 52 patients) were followed since July, 2003, to October, 2005. With a minimum follow-up period of 12 months, we evaluated the early post-operative dislocation rate. RESULTS: The early postoperative hip-dislocation rate for the group who did not undergo posterior capsular repair appeared to be substantially greater (6.38% versus 0%) than the corresponding figure for the group the members of which underwent posterior capsular repair. In addition, patient demographics and the orientation of acetabular components for the replaced hip joints, as presented in postoperative radiographs, did not differ between the two groups. CONCLUSION: Thus, surgeons should include posterior capsular repair as an important step in the surgical procedures of posterolateral approach for all THA in order to reduce the likelihood of early hip dislocation subsequent to THA.

Perioperative celecoxib administration for pain management after total knee arthroplasty - a randomized, controlled study.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended for multimodal postoperative pain management. We evaluated opioid-sparing effects and rehabilitative results after perioperative celecoxib administration for total knee arthroplasty. METHODS: This was a prospective, randomized, observer-blind control study. Eighty patients that underwent total knee arthroplasty were randomized into two groups of 40 each. The study group received a single 400 mg dose of celecoxib, one hour before surgery, and 200 mg of celecoxib every 12 hours for five days, along with patient-controlled analgesic (PCA) morphine. The control group received only PCA morphine for postoperative pain management. Visual analog scale (VAS) pain scores, active range of motion (ROM), total opioid use and postoperative nausea/vomiting were analyzed. RESULTS: Groups were comparable for age, pre-operative ROM, operation duration and intraoperative blood loss. Resting VAS pain scores improved significantly in the celecoxib group, compared with controls, at 48 hrs (2.13 +/- 1.68 vs. 3.43 +/- 1.50, p = 0.03) and 72 hrs (1.78 +/- 1.66 vs. 3.17 +/- 2.01, p = 0.02) after surgery. Active ROM also increased significantly in the patients that received celecoxib, especially in the first 72 hrs [40.8 degrees +/- 17.3 degrees vs. 25.8 degrees +/- 11.5 degrees , p = 0.01 (day 1); 60.7 degrees +/- 18.1 degrees vs. 45.0 degrees +/- 17.3 degrees , p = 0.004 (day 2); 77.7 degrees +/- 15.1 degrees vs. 64.3 degrees +/- 16.9 degrees , p = 0.004 (day 3)]. Opioid requirements decreased about 40% (p = 0.03) in the celecoxib group. Although patients suffering from post-operative nausea/vomiting decreased from 43% in control group to 28% in celecoxib group, this was not significant (p = 0.57). There were no differences in blood loss (intra- and postoperative) between the groups. Celecoxib resulted in no significant increase in the need for blood transfusions. CONCLUSION: Perioperative celecoxib significantly improved postoperative resting pain scores at 48 and 72 hrs, opioid consumption, and active ROM in the first three days after total knee arthroplasty, without increasing the risks of bleeding. TRIAL REGISTRATION: Clinicaltrials.gov NCT00598234.

Repair of porcine articular cartilage defect with a biphasic osteochondral composite.

Autologous chondrocyte implantation (ACI) has been recently used to treat cartilage defects. Partly because of the success of mosaicplasty, a procedure that involves the implantation of native osteochondral plugs, it is of potential significance to consider the application of ACI in the form of biphasic osteochondral composites. To test the clinical applicability of such composite construct, we repaired osteochondral defect with ACI at low cell-seeding density on a biphasic scaffold, and combined graft harvest and implantation in a single surgery. We fabricated a biphasic cylindrical porous plug of DL-poly-lactide-co-glycolide, with its lower body impregnated with beta-tricalcium phosphate as the osseous phase. Osteochondral defects were surgically created at the weight-bearing surface of femoral condyles of Lee-Sung mini-pigs. Autologous chondrocytes isolated from the cartilage were seeded into the upper, chondral phase of the plug, which was inserted by press-fitting to fill the defect. Defects treated with cell-free plugs served as control. Outcome of repair was examined 6 months after surgery. In the osseous phase, the biomaterial retained in the center and cancellous bone formed in the periphery, integrating well with native subchondral bone with extensive remodeling, as depicted on X-ray roentgenography by higher radiolucency. In the chondral phase, collagen type II immunohistochemistry and Safranin O histological staining showed hyaline cartilage regeneration in the experimental group, whereas only fibrous tissue formed in the control group. On the International Cartilage Repair Society Scale, the experimental group had higher mean scores in surface, matrix, cell distribution, and cell viability than control, but was comparable with the control group in subchondral bone and mineralization. Tensile stress-relaxation behavior determined by uni-axial indentation test revealed similar creep property between the surface of the experimental specimen and native cartilage, but not the control specimen. Implanted autologous chondrocytes could survive and could yield hyaline-like cartilage in vivo in the biphasic biomaterial construct. Pre-seeding of osteogenic cells did not appear to be necessary to regenerate subchondral bone.

Injecting partially digested cartilage fragments into a biphasic scaffold to generate osteochondral composites in a nude mice model.

This study proposed a novel scaffold with heterogeneous morphology that mimics the natural tissue. Its upper part contains a hollow cavity surrounded by a wall of poly(L-lactic-co-glycolic acid) (PLGA) porous membrane for injecting cartilage tissue and cells. An interconnecting porous structure located under the hollow cavity was made of composite materials that combined PLGA and beta-tricalcium phosphate (beta-TCP) to simulate the subchondral bone. Adult pig articular cartilage was cut and sieved into small fragments. The tissue fragments was partially digested by 0.1% collagenase for 0, 2, 4, and 6 h and injected into the hollow cavity of the biphasic scaffold. The biphasic scaffolds were then implanted into the subcutaneous pocket of nude mice for 4 weeks. No tissue bonding or new cartilaginous tissue formation was identified in the cartilage fragment without enzymatic treatment. The cartilage fragments digested with 2 h of collagenase digestion were partially integrated after implantation. The integrative properties of the cartilage fragment depended on the extent of enzymatic digestion. Releasing cells at the tissue surface enhanced confluence and bonding of the cartilage fragment matrix. Complete integration of the cartilage fragments and cartilage remodeling were achieved by digestion of the tissue fragments with 4 h of enzymatic treatment. The neocartilage grew from the upper hollow cavity into the lower PLGA/beta-TCP porous structure, forming an interface similar to that formed between cartilage and subchondral bone. This study combined the osteochondral scaffold and limited cartilage tissues to generate cartilage tissue in vivo intending for repairing full-thickness articular cartilage defects.

Imaging human bone marrow stem cell morphogenesis in polyglycolic acid scaffold by multiphoton microscopy.

The noninvasive imaging of tissue engineering constructs is vital for understanding the physiological changes in construct formation and the design of improved products for therapeutic purposes. In this work, we use the combination of multiphoton autofluorescence and second harmonic generation (SHG) microscopy to image the physiological changes to the engineered constructs of human mesenchymal stem cells seeded in a polyglycolic acid (PGA) scaffold under induction by chondrogenic transforming growth factor-beta3. Without histological procedures, we found that multiphoton autofluorescence is useful for imaging the PGA scaffold and stem cells while SHG is useful for following the progress of extracellular matrix (ECM) formation. We found that the initial ECM formation tends to align along the PGA scaffold orientation and progressive induction alters the scaffold conformation, indicating that biomechanical forces or the chemical environment generated by chondrogenesis is sufficient for scaffold reorganization. Our results suggest that in the future this approach may be used for real-time monitoring of the physiological processes associated with tissue engineering.