Introduction and Objective. Postoperative pain control in shoulder surgery is challenging even in arthroscopic procedures. Acute postoperative pain can last up to 48hrs despite using multimodal analgesia. Different techniques have been used to control acute pain following shoulder surgery. The most common technique currently used in shoulder surgery at the elective orthopaedic centre in Leeds is a combination of general anaesthetic (GA) and interscalene block (ISB). ISB maybe very effective, however, carries many risks and potential side effects such as brachial plexus injury and paralysis of the vagus and laryngeal recurrent nerves as well as cervical sympathetic nerve and pneumothorax. ISB can also be associated with higher incidence of neurological deficit compared to other peripheral nerve blocks; up to 14% at 10 days in some cases. As such we decided to examine the use of ISB for achieving pain control in our elective unit. Materials and Methods. A prospective consecutive series of 217 patients undergoing shoulder surgery were studied. These were grouped into 10 groups. All procedures were arthroscopic apart from shoulder arthroplasty procedures such as hemiarthroplasty and total shoulder replacements (TSRs). The choice of regional anaesthesia was ISB with GA as standard practice. Visual analogue scores (VAS) at 0hrs, 1hr, 2hrs, 4hrs and 6hrs; and total opiates intake were recorded. A one-way single factor ANOVA was used as preferred statistical analytical method to determine whether there is a difference in VAS scores and total opiates intake amongst the groups. Postoperative analgesics were used for pain relief, although these were not standardised. Results. In total shoulder replacement group, although the RSR group used more morphine on average compared to the ASR group (Mean morphine intake 6.5mg vs 3mg), this was not statistically significant (F<Fcrit; p value= 0.19). When comparing all the arthroplasty groups, the difference in mean morphine intake was also statistically not significant (F<Fcrit; p value=0.24). However, when comparing all 10 groups’ morphine intake there was a statistically significant difference amongst these groups (F>F crit; p value=0.03). Interestingly, there was a statistically significant difference in VAS at 0hrs (F>Fcrit p value=0.01); 1hrs (F>Fcrit; p value=0.00), and at 6hrs (F>Fcrit; p value=0.02) when comparing all 10 groups. Conclusions. ISB is an effective technique in achieving pain control in shoulder surgery; however, there are still variations in analgesic needs amongst groups and the use of alternative techniques should be thus explored. A future prospective study looking at acute pain for a longer period of time after shoulder surgery would explore the effectiveness of ISB in achieving pain control consistent with rehabilitation requirements

The current study aims to find the role of Enhance Recovery Pathway (ERP) as a multidisciplinary approach aimed to expedite rapid recovery, reduce LOS, and minimize morbidity associated with Non Fusion Anterior Scoliosis Correction (NFASC) surgery. A retrospective analysis of 35 AIS patients who underwent NFASC with Lenke 1 and Lenke 5 curves with a minimum of 1 year of follow-up was done. Patient demographics, surgical details, postoperative analgesia, mobilization, length of stay (LOS), patient satisfaction survey score with respect to information and care, and 90 days complications were collected. The cohort included 34 females and 1 male with a mean age of 15.2 years at the time of surgery. There were 16 Lenke 1 and 19 Lenke 5 in the study. Mean preoperative major thoracic and thoracolumbar/lumbar Cobb's angle were 52˚±7.6˚ and 51˚±4.5˚ respectively. Average blood loss and surgical time were 102 ±6.4 ml and 168 ± 10.2 mins respectively. Average time to commencing solid food was 6.5±1.5 hrs. Average time to mobilization following surgery was 15.5± 4.3 hrs. The average duration to the stopping of the epidural was 42.5±3.5 hrs. The average dose of opioid consumption intraoperatively was 600.5±100.5 mcg of fentanyl i.v. and 12.5±4.5 mg morphine i.v. Postoperatively opioids were administered via an epidural catheter at a dose of 2 mg of morphine every 24 hours up to 2 days and an infusion of 2mcg/hr of fentanyl along with 0.12-0.15% ropivacaine. The average duration to transition to oral analgesia was 55.5±8.5 hrs .20 patients had urinary catheter and the average time to removal of the catheter was 17.5±1.4 hrs. 25 patients had a chest tube and the average time to remove of chest tube was 25.5±3.2 hrs. The average length of hospital stay was 3.1±0.5 days. No patient had postoperative ileus or requirement of blood transfusion or any other complications. No correlation was found between LOS and initial cobb angle. The application of ERP in AIS patients undergoing NFASC results in reduced LOS and indirectly the cost, reduced post-operative opioid use, and overall improve patient satisfaction score

Background. Orthopedic trauma patients can have significant pain management requirements. Patient satisfaction has been associated with pain control and narcotic use in previous studies. Due to the multifactorial nature of pain, various injury patterns, and differences in pain tolerances the relationship between patient factors and narcotic requirements are poorly understood. The purpose of this study is to compare patient demographics for trauma patients requiring high doses of narcotics for pain control versus those with more minimal requirements. Methods. Our study sample included 300 consecutive trauma activations who presented to our emergency department during the 2015 calendar year. Opioids given to the patients during their hospital stay were converted to oral morphine equivalents using ratios available from the current literature. Patients were placed into two groups including those who were in the top 10% for average daily inpatient oral morphine equivalents and the other group was composed of the remaining patients. In addition to morphine equivalents, patient age, gender, injury severity score, length of stay, number of readmissions and urine toxicology results were also recorded. Injury severity score (ISS), morphine equivalents, and patient age were evaluated with the Shapiro-Wilk test of normality. Comparisons were performed with the Mann-Whitney U test. Between group comparisons for positive urine toxicology screen and gender were performed with Chi square and Fisher exact test. Pearson correlations were calculated between injury severity score, average daily oral morphine equivalents, and length of stay. P-value of 0.05 was used to represent significance. Statistical comparisons were made using SPSS version 23 (IBM, Aramonk, NY). Results. Median average daily morphine equivalents in the 10% of patients receiving the highest doses was 86.30 and 12.95 for the bottom 90%. The difference was statistically significant (p<0.001). The median ISS between the 2 groups was significant (p=0.018). There was no significant difference in age, readmission rate, and urine toxicology results. Patients in the top 10% were more likely to be male (p=0.003). Median length of stay for the top 10% group and bottom 90% group was 4 days and 2 days, respectively (p=0.005). No correlation between injury severity score and length of stay was found (p=0.475). A weak correlation of 0.115 was found between morphine equivalents and length of stay (p=0.047). Discussion. Our study shows male gender and ISS were correlated with higher oral morphine equivalents for the 10% of patients receiving the highest daily amounts when compared to the reaminder of the cohort. There was a significantly increased length of stay in the patients receiving higher narcotic doses. Whether this is due to ISS or increase in narcotics is unclear. However, positive correlation was not found between ISS and length of stay

Excessive opioid prescriptions after total joint arthroplasty (TJA) increase risks for adverse opioid related events, chronic opioid use, and increase the availability of opioids for unlawful diversion. Thus, decreasing postoperative prescriptions may improve quality after TJA. Concerns exist that a decrease in opioids prescribed may increase complications such as readmissions, emergency department (ED) visits or worsened patient reported outcomes (PROs). The purpose of this quality improvement study was to explore whether a reduction in opioids prescribed after TJA resulted in increased complications. Methods: Data originated from a statewide arthroplasty database (MARCQI). The database collects over 96% of all TJA performed in the state of Michigan, USA. Data was prospectively abstracted and included OMEs prescribed at discharge, readmissions, ED visits within 30 days and PROs. Data was collected one year before and after the creation of an opioid prescribing protocol that had decreased prescriptions by approximately 50% in opioid naive and tolerant patients. Trends were monitored using Shewhart control charts. 84,998 TJA over two-years were included. All groups showed a reduction in opioids prescribed. Importantly, no increased complications occurred concomitant to this reduction. No increases in ED visits or readmissions, and no decreases in KOOSJR/HOOSJR/PROMIS10 scores were noted in any of the groups. Using large data sets and registries can drive performance and improve quality. The MARCQI Postoperative opioid prescription recommendations and performance measures decreased total oral morphine equivalents prescribed over a large and diverse population by approximately 50% without decreasing PROs or increasing ED visits or hospital readmissions. A reduction in opioids prescribed after TJA can be accomplished safely and without an increase in complications across a large population

Background. Pain control following knee replacement (TKR) surgery is often poor. Moderate to severe pain is often reported in the first 48 hours following surgery requiring opiate analgesia. The Local Infiltration Anaesthetic (LIA) technique has been described as a method to reduce post operative pain. In this study we report on our experience using LIA in addition to the PainKwell system (Peak Medical) of continuous infusion intra-articularly, of 0.25% bupivacaine at 4–5 mls/hour for 48 hours post surgery. The PainKwell catheter is placed in the knee joint during surgery. Methods. Between the June 2012 and Sep 2012, 62 patients undergoing primary TKR were prospectively followed up. All patients studied had spinal anaesthesia (SA) with diamorphine. Group 1. GA. No LIA and no PainKwell. 20 patients. Group 2. SA plus LIA plus PainKwell for 48 hours post operatively with catheter placed anteriorly under the patella. 21 patients. Group 3. SA plus LIA plus PainKwell for 48 hours post operatively with catheter placed posteriorly in the knee joint. 21 patients. Results. The patients without LIA or PainKwell required more morphine in the first 12 hours postoperative period than the other groups. Seventy percent (n=14) of these group 1 patients required 10mg morphine following TKR compared to only 2% (n=1) of patients requiring 10mg of morphine when LIA and PainKwell as used. The increased morphine requirement continued for 48 hours postoperatively in group 1, whereas none of the patients in groups 2 or 3 required morphine after 36 hours. Fewer patients suffered from nausea and vomiting or urinary retention in the group with LIA and PainKwell

Introduction and Objective. Objectives: To determine the effectiveness of LIA compared to ACB in providing pain relief and reducing opiates usage in hamstring graft ACL reconstructions. Materials and Methods. In a consecutive series of hamstring graft ACL reconstructions, patients received three different regional and/or anaesthetic techniques for pain relief. Three groups were studied: group 1: general anaesthetic (GA)+ ACB (n=38); group 2: GA + ACB + LIA (n=31) and group 3: GA+LIA (n=36). ACB was given under ultrasound guidance. LIA involved infiltration at skin incision site, capsule, periosteum and in the hamstring harvest tunnel. Analgesic medications were similar between the three groups as per standard multimodal analgesia (MMA). Patients were similar in demographics distribution and surgical technique. The postoperative pain and total morphine requirements were evaluated and recorded. The postoperative pain was assessed using the visual analogue scores (VAS) at 0hrs, 2hrs, 4hrs, weight bearing (WB) and discharge (DC). Results. There was no statistically significant difference in opiates intake amongst the three groups. When comparing VAS scores; there were no statistical difference between the groups at any of the time intervals that VAS was measured. However, the GA+LIA group hospital's LOS (m=2.31hrs, SD=0.75) was almost half that of GA+ACB group (m=4.24hrs, SD=1.08); (conditions t(72)=8.88; p=0.000). There was no statistical significance in the incidence of adverse effects amongst the groups. Conclusions. The LIA technique provided equally good pain relief following hamstring graft ACL reconstructions when compared to ACB, while allowing for earlier rehabilitation, mobilisation and discharge

Background. Narcotics are commonly prescribed for pain control of orthopedic trauma but injury pattern and severity, in addition to patient factors, result in varying dosing requirements. These factors, coupled with increasing pressure to reduce narcotic consumption, highlight the importance of narcotic stewardship and comprehension of patient factors leading to higher pain control demands. The purpose of this study is to understand whether or not narcotic consumption is greater in patients who present to the emergency department with positive drug screen (utox) for illicit substances. Methods. We performed a retrospective chart review of 300 consecutive trauma activations during the 2015 calendar year. Of the patient cohort, 226 patients received a utox screen which represents the cohort for this study. Utox screen included amphetamines, barbiturates, benzodiazepines, cocaine, ethanol, methadone, phencyclidine, and tetrahydrocannabinol. Opioids given hospital stay were converted to oral morphine equivalents using ratios available in the current literature. The average daily equivalent was calculated for their total hospital stay and recorded. Patient injury severity score (ISS), age, gender, length of stay, readmission rates were also recorded. Statistical comparisons were made using SPSS version 23 (IBM, Aramonk, NY). Data distributions were examined with the Shapiro-Wilk test of normality between group comparisons were made with Mann Whitney U tests. Chi squared test was used to evaluate categorical data. Significance was set at p=0.05. Results. There were 108 (48%) positive utox tests of the 226 that received a utox test. There was no difference in gender distribution or age between the 2 groups. The calculated morphine equivalent consumption of the positive utox patient cohort was compared against the negative utox group. The median daily oral morphine equivalents in the positive utox group was 23.85 versus 12.05 for those with a negative utox screen. This was found to be statistically significant with a p value of 0.014. The average length of stay for the positive utox group was 3 days versus 2 days for the negative utox group. This also was statistically significant with a p value of 0.009. There was no statistical significance for ISS (5 in utox positive versus 5 in utox negative patients) nor was there any significance found in the rate of readmissions. Discussion. Our study shows that infividuals found to have positive utox screening for illicit drug use require more opioids for pain control and have longer hospital stays. These increased resource requirements exist despite no statistically significant difference in ISS. The high rate of positive findings and differences in patient clinical course support continued utox screening in trauma activation patients. When treating these patients, physicians should be aware of potential differences in pain management strategies and would likely benefit from multimodal pain control progam

Background. Hip arthroplasties are associated with high postoperative pain scores. In some reports, moderate to severe pain was 58% on the first day postoperatively in total hip replacements (THRs). Several techniques are currently used at our institution to tackle acute pain following THRs. These include: 1) Spinal anaesthetic (SA) with Diamorphine only; 2) General anaesthetic (GA) only; 3) SA with local infiltration anaesthetic mixture 1 (LIA1,). Mixture 1 consisted of ropivacaine, adrenaline, and ketorolac; 4) SA with LIA mixture 2 (LIA2). Mixture 2 consisted of bupivacaine and adrenaline; 5) SA with LIA1 and PainKwell pump system. In this study we report on the techniques of acute pain control following THR at our regional centre for elective primary THRs. Methods. Between June 2011 and July 2014, 173 consecutive patients undergoing primary THR using the posterior approach were prospectively followed up. Group 1. GA only. 31 patients, Group 2. SA only. 37 patients, Group 3. SA plus LIA1 only. 38 patients, Group 4. SA plus LIA2 only, 34 patients, Group 5. SA plus LIA1 plus PainKwell Pump System for 48 hours. 33 patients. Results. Fewer patients required opiate analgesia when LIA plus PainKwell pump system was used compared to the other groups. The highest significance was at 0–12 hrs for patients requiring up to 20mg morphine usage (χ2(2) = 46.713, p = 0.000); and 0–12hrs for patients requiring 30mg morphine usage (χ2(2) = 46.310, p = 0.000). There were no infections, DVTs or PEs in any group. One patient in group 3 suffered a stroke (ASA 4). A Kruskal-Wallis H test also showed that there was a statistically significant difference in morphine usage across groups 1, 2, 3, 4, and 5. Conclusion. We recommend the use of LIA with PainKwell pump system continuous infusion as an efficacious method to control pain following THR

We aimed to determine the impact of anaesthetic techniques on post-operative analgesic utilisation in people undergoing total knee arthroplasty. We conducted a prospective study at a district general hospital to assess post-operative analgesia use via patient controlled analgesia (PCA) in patients undergoing a elective total knee arthroplasty. Subjects were divided into three groups; group 1 (general anaesthetic and local nerve block, n = 39), group 2 (spinal only, n= 39) and group 3 (general anaesthetic only, n = 38). The primary outcome measure was post-operative morphine consumption through a PCA within the first 24 hours. All subjects were followed up post-operatively by a dedicated pain control nurse. Data was analysed using SPSS version 17 for Windows (SPSS Inc, Chicago, IL, USA). Results are reported as mean (SD) unless stated otherwise. No significant difference in the age or sex distribution between groups was demonstrable. There was no statistical difference in the average usage of morphine when comparing Group 1 compared to group 2, (77.57 (49.56) vs 65.80 (44.71), p=0.27), group 1 compared to group 3, (77.57 (49.56) vs 77.80 (45.52) p=0.98) and finally group 2 compared to group 3, (65.80 (44.71) vs 77.80 (45.52), p=0.25). In this cohort of patients undergoing total knee arthroplasty the anaesthetic technique used does not appear to have an influence on the post-operative pain management

Background. Adequate pain management is mandatory for patients' early rehabilitation and improvement of outcome after total knee arthroplasty (TKA). Conventional pain management, consisted of mainly opioids, has some adverse effects such as dizziness and nausea. Motor blockade occasionally resulted from epidural analgesics. A novel multimodal analgesic strategy with peripheral nerve block, peri-articular injection (PAI) and intravenous patient controlled analgesia (IVPCA) were utilized for our patients receiving TKA. In this study, we compared the clinical efficacy and adverse effects in the group of multimodal analgesia (MA) or epidural analgesia alone. Methods. One hundred and eighteen patients undergoing TKA with spinal anesthesia were enrolled. Patients of TKA received either our protocol of multimodal analgesia or patient controlled epidural analgesia (PCEA) alone. MA included ultrasound guided nerve block in femoral and obturator nerves before spinal anesthesia, and PAI mixed with NSAID, morphine, ropivacaine and epinephrine, as well as IVPCA after surgeries. The analgesic effect with numeric rating scale (NRS) and occurrence of adverse effects, including motor blockade, numbness, postoperative nausea/vomiting (PONV), and dizziness were recorded for all patients. Results. Thirty-one patients received MA, and eighty-seven patients received PCEA. No significant difference of NRS in MA and PCEA group within 24 hours after surgery either in rest (0.2 ± 1 compared with 0.22 ± 0.98; p = 0.930) or motion (0.40 ± 1.56 compared with 0.31± 1.23; p = 0.764). MA group sustained lesser motor blockade than PCEA (6.45% compared with 22.98%; p = 0.028) beyond 24 hours after surgery. The occurrence of numbness is lower in MA group (18.52%) compared with PCEA group(43.33%) (p=0.031). No statistic difference of PONV and dizziness is noted between two groups. However, there is a trend that lesser PONV and dizziness occurred in MA group than PCEA group. Conclusion. TKA patients receiving either MA or PCEA have adequate analgesic efficacy after surgeries. MA group has a lower incidence of motor blockade and PONV than PCEA. This multimodal analgesia proposed here has shown patients' safety and improved pain control after TKA, decreased narcotics use and their associated side effects. Besides, lesser motor blockade and adequate pain relief may encourage patient's early rehabilitation

Robust evidence on the effectiveness of peri-operative local anaesthetic infiltration (LAI) is required before it is incorporated into the pain management regimen for patients receiving total hip replacement (THR). We assessed the effectiveness of LAI using a systematic review and a fully powered randomised controlled trial (RCT) with economic evaluation. We searched MEDLINE, Embase and Cochrane databases for RCTs of peri-operative LAI in patients receiving THR. Two reviewers screened abstracts, extracted data, and liaised with authors. Outcomes were pain, opioid use, mobilisation, hospital stay and complications. If feasible, we conducted meta-analysis. In the APEX RCT, we randomised 322 patients awaiting THR to receive additional peri-operative LAI (60mls 0.25% bupivacaine plus adrenaline) or standard anaesthesia alone. Post-operatively, all patients received patient-controlled morphine. The primary outcome was joint pain severity (WOMAC-Pain) at 12 months. Patients and outcome assessors were blinded to allocation. Within APEX, cost-effectiveness was assessed from the health and social-care perspective in relation to quality adjusted life years (QALYs) and WOMAC-Pain at 12-months. Resource use was collected from hospital records and patient questionnaires. In the systematic review, we identified 13 studies (909 patients). Patients undergoing THR receiving LAI experienced greater pain reduction at 24 hours at rest, standardised mean difference (SMD) −0.61 (95%CI −1.05, −0.16; p=0.008) and at 48 hours during activity, SMD −0.43 (95%CI −0.78, −0.09; p=0.014). Patients receiving LAI spent fewer days in hospital, used less opioids and mobilised earlier. Complications were similar between groups. Long-term outcomes were not a focus of these studies. In the APEX RCT, pain levels in hospital were broadly similar between groups, probably due to patient-controlled analgesia. Opioid use was similar between groups. Time to mobilisation and discharge were largely dependent on local protocols and did not differ between groups. Patients receiving LAI were less likely to report severe pain at 12 months than those receiving standard care, odds ratio 10.2 (95%CI 2.1, 49.6; p=0.004). Complications were similar between groups. In the economic evaluation, LAI was associated with lower costs and greater cost-effectiveness than standard care. Using a £20,000 per QALY threshold, the incremental net monetary benefit was £1,125 (95%CI £183, £2,067) and the probability of being cost-effective was greater than 98 %. The evidence suggests that peri-operative LAI is a cost-effective intervention for reducing acute and chronic post-surgical pain after THR

Robust evidence on the effectiveness of peri-operative local anaesthetic infiltration (LAI) is required before it is incorporated into the pain management regimen for patients receiving total knee replacement (TKR). To assess the effectiveness of peri-operative LAI for pain management in patients receiving TKR we conducted a systematic review, fully powered randomised controlled trial (RCT) and economic evaluation. We searched MEDLINE, Embase and Cochrane databases for RCTs of peri-operative LAI in patients receiving TKR. Two reviewers screened abstracts and extracted data. Outcomes were pain, opioid use, mobilisation, hospital stay and complications. Authors were contacted if required. When feasible, we conducted meta-analysis with studies analysed separately if a femoral nerve block (FNB) was provided. In the APEX RCT, we randomised 316 patients awaiting TKR to standard anaesthesia which included FNB, or to the same regimen with additional peri-operative LAI (60mls 0.25% bupivacaine plus adrenaline). Post-operatively, all patients received patient-controlled morphine. The primary outcome was joint pain severity (WOMAC-Pain) at 12 months. Patients and outcome assessors were blinded to allocation. Within APEX, cost-effectiveness was assessed from the health and social-care perspective in relation to quality adjusted life years (QALYs) and WOMAC-Pain at 12-months. Resource use was collected from hospital records and patient questionnaires. In the systematic review, 23 studies including 1,439 patients were identified. Compared with patients receiving no intervention, LAI reduced WOMAC-Pain by standardised mean difference (SMD) −0.40 (95%CI −0.58, −0.22; p<0.001) at 24 hours at rest and by SMD −0.27 (95%CI −0.50, −0.05; p=0.018) at 48 hours during activity. In three studies there was no difference in pain at any time point between randomised groups where all patients received FNB. Patients receiving LAI spent fewer days in hospital, used less opioids and mobilised earlier. Complications were similar between groups. Few studies reported long-term outcomes. In the APEX RCT, pain levels in hospital were broadly similar between groups. Overall opioid use was similar between groups. Time to mobilisation and discharge were largely dependent on local protocols and did not differ between groups. There were no differences in pain outcomes between groups at 12 months. In the economic evaluation, LAI was marginally associated with lower costs. Using the NICE £20,000 per QALY threshold, the incremental net monetary benefit was £264 (95%CI, −£710, £1,238) and the probability of being cost-effective was 62%. Although LAI appeared to have some benefit for reduced pain in hospital after TKR there was no evidence of pain control additional to that provided by femoral nerve block, however it would be cost-effective at the current NICE thresholds

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We have developed an animal model to examine the formation of heterotopic ossification using standardised muscular damage and implantation of a beta-tricalcium phosphate block into a hip capsulotomy wound in Wistar rats. The aim was to investigate how cells originating from drilled femoral canals and damaged muscles influence the formation of heterotopic bone. The femoral canal was either drilled or left untouched and a tricalcium phosphate block, immersed either in saline or a rhBMP-2 solution, was implanted. These implants were removed at three and 21 days after the operation and examined histologically, histomorphometrically and immunohistochemically.

Bone formation was seen in all implants in rhBMP-2-immersed, whereas in those immersed in saline the process was minimal, irrespective of drilling of the femoral canals. Bone mineralisation was somewhat greater in the absence of drilling with a mean mineralised volume to mean total volume of 18.2% (sd 4.5) versus 12.7% (sd 2.9, p < 0.019), respectively.

Our findings suggest that osteoinductive signalling is an early event in the formation of ectopic bone. If applicable to man the results indicate that careful tissue handling is more important than the prevention of the dissemination of bone cells in order to avoid heterotopic ossification.

Gene therapy with insulin-like growth factor-1 (IGF-1) increases matrix production and enhances chondrocyte proliferation and survival in vitro. The purpose of this study was to determine whether arthroscopically-grafted chondrocytes genetically modified by an adenovirus vector encoding equine IGF-1 (AdIGF-1) would have a beneficial effect on cartilage healing in an equine femoropatellar joint model.

A total of 16 horses underwent arthroscopic repair of a single 15 mm cartilage defect in each femoropatellar joint. One joint received 2 × 10⁷ AdIGF-1 modified chondrocytes and the contralateral joint received 2 × 10⁷ naive (unmodified) chondrocytes. Repairs were analysed at four weeks, nine weeks and eight months after surgery. Morphological and histological appearance, IGF-1 and collagen type II gene expression (polymerase chain reaction, in situ hybridisation and immunohistochemistry), collagen type II content (cyanogen bromide and sodium dodecyl sulphate-polyacrylamide gel electrophoresis), proteoglycan content (dimethylmethylene blue assay), and gene expression for collagen type I, matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, aggrecanase-1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and TIMP-3 were evaluated.

Genetic modification of chondrocytes significantly increased IGF-1 mRNA and ligand production in repair tissue for up to nine weeks following transplantation. The gross and histological appearance of IGF-1 modified repair tissue was improved over control defects. Gross filling of defects was significantly improved at four weeks, and a more hyaline-like tissue covered the lesions at eight months. Histological outcome at four and nine weeks post-transplantation revealed greater tissue filling of defects transplanted with genetically modified chondrocytes, whereas repair tissue in control defects was thin and irregular and more fibrous. Collagen type II expression in IGF-1 gene-transduced defects was increased 100-fold at four weeks and correlated with increased collagen type II immunoreaction up to eight months.

Genetic modification of chondrocytes with AdIGF-1 prior to transplantation improved early (four to nine weeks), and to a lesser degree long-term, cartilage healing in the equine model.

The equine model of cartilage healing closely resembles human clinical cartilage repair. The results of this study suggest that cartilage healing can be enhanced through genetic modification of chondrocytes prior to transplantation.