Tackling the Challenges of Graft Healing After Anterior Cruciate Ligament Reconstruction—Thinking From the Endpoint

Anterior cruciate ligament (ACL) tear is common in sports and accidents, and accounts for over 50% of all knee injuries. ACL reconstruction (ACLR) is commonly indicated to restore the knee stability, prevent anterior–posterior translation, and reduce the risk of developing post-traumatic osteoarthritis. However, the outcome of biological graft healing is not satisfactory with graft failure after ACLR. Tendon graft-to-bone tunnel healing and graft mid-substance remodeling are two key challenges of biological graft healing after ACLR. Mounting evidence supports excessive inflammation due to ACL injury and ACLR, and tendon graft-to-bone tunnel motion negatively influences these two key processes. To tackle the problem of biological graft healing, we believe that an inductive approach should be adopted, starting from the endpoint that we expected after ACLR, even though the results may not be achievable at present, followed by developing clinically practical strategies to achieve this ultimate goal. We believe that mineralization of tunnel graft and ligamentization of graft mid-substance to restore the ultrastructure and anatomy of the original ACL are the ultimate targets of ACLR. Hence, strategies that are osteoinductive, angiogenic, or anti-inflammatory should drive graft healing toward the targets. This paper reviews pre-clinical and clinical literature supporting this claim and the role of inflammation in negatively influencing graft healing. The practical considerations when developing a biological therapy to promote ACLR for future clinical translation are also discussed.

Neovaginoplasty for radiation-induced vaginal stenosis using Nile Tilapia Fish Skin as a biological graft

Tilapia skin showed good results when used as a biological graft for surgical management of Mayer–Rokitansky–Küster–Hauser syndrome. Thus, our researchers considered the use of this biomaterial for neovaginoplasty in radiation-induced vaginal stenosis. We report the case of a 41-year-old female patient with a total occlusion of the vaginal canal after radiotherapy for vaginal cancer. McIndoe neovaginoplasty using tilapia skin as a scaffold for proliferation of new vaginal epithelium was performed. Initially, laparoscopic dissection of the rectovaginal septum and vesicovaginal space spaces was conducted. In the vaginal surgical time, a transverse transmural incision was made in the scarred vaginal reminiscent followed by blunt dissection and insertion of an acrylic mold covered with tilapia skin. Good anatomical and functional outcomes were noted. Vaginal reconstruction with tilapia skin seems to be an excellent option for patients with radiation-induced vaginal stenosis due to its wide availability, easy application and high effectiveness.

Clinical effectiveness and cost-effectiveness of surgical options for the management of anterior and/or posterior vaginal wall prolapse: two randomised controlled trials within a comprehensive cohort study – results from the PROSPECT Study

BackgroundThe use of mesh in prolapse surgery is controversial, leading to a number of enquiries into its safety and efficacy.ObjectiveTo compare synthetic non-absorbable mesh inlay, biological graft and mesh kit with a standard repair in terms of clinical effectiveness, adverse effects, quality of life (QoL), costs and cost-effectiveness.DesignTwo randomised controlled trials within a comprehensive cohort (CC) study. Allocation was by a remote web-based randomisation system in a 1 :1 : 1 ratio (Primary trial) or 1 : 1 : 2 ratio (Secondary trial), and was minimised on age, type of prolapse repair planned, need for a concomitant continence procedure, need for a concomitant upper vaginal prolapse procedure and surgeon. Participants and outcome assessors were blinded to randomisation; participants were unblinded if they requested the information. Surgeons were not blinded to allocated procedure.SettingThirty-five UK hospitals.ParticipantsPrimary study: 2474 women in the analysis (including 1348 randomised) having primary anterior or posterior prolapse surgery.Secondary study: 398 in the analysis (including 154 randomised) having repeat anterior or posterior prolapse surgery.CC3: 215 women having either uterine or vault prolapse repair.InterventionsAnterior or posterior repair alone, or with mesh inlay, biological graft or mesh kit.Main outcome measuresProlapse symptoms [Pelvic Organ Prolapse Symptom Score (POP-SS)]; prolapse-specific QoL; cost-effectiveness [incremental cost per quality-adjusted life-year (QALY)].ResultsPrimary trials: adjusting for baseline and minimisation covariates, mean POP-SS was similar for each comparison {standard 5.4 [standard deviation (SD) 5.5] vs. mesh 5.5 (SD 5.1), mean difference (MD) 0.00, 95% confidence interval (CI) –0.70 to 0.71; standard 5.5 (SD 5.6) vs. graft 5.6 (SD 5.6), MD –0.15, 95% CI –0.93 to 0.63}. Serious non-mesh adverse effects rates were similar between the groups in year 1 [standard 7.2% vs. mesh 7.8%, risk ratio (RR) 1.08, 95% CI 0.68 to 1.72; standard 6.3% vs. graft 9.8%, RR 1.57, 95% CI 0.95 to 2.59]. There were no statistically significant differences between groups in any other outcome measure. The cumulative mesh complication rates over 2 years were 2 of 430 (0.5%) for standard repair (trial 1), 46 of 435 (10.6%) for mesh inlay and 2 of 368 (0.5%) for biological graft. The CC findings were comparable. Incremental costs were £363 (95% CI –£32 to £758) and £565 (95% CI £180 to £950) for mesh and graft vs. standard, respectively. Incremental QALYs were 0.071 (95% CI –0.004 to 0.145) and 0.039 (95% CI –0.041 to 0.120) for mesh and graft vs. standard, respectively. A Markov decision model extrapolating trial results over 5 years showed standard repair had the highest probability of cost-effectiveness, but results were surrounded by considerable uncertainty.Secondary trials: there were no statistically significant differences between the randomised groups in any outcome measure, but the sample size was too small to be conclusive. The cumulative mesh complication rates over 2 years were 7 of 52 (13.5%) for mesh inlay and 4 of 46 (8.7%) for mesh kit, with no mesh exposures for standard repair.ConclusionsIn women who were having primary repairs, there was evidence of no benefit from the use of mesh inlay or biological graft compared with standard repair in terms of efficacy, QoL or adverse effects (other than mesh complications) in the short term. The Secondary trials were too small to provide conclusive results.LimitationsWomen in the Primary trials included some with a previous repair in another compartment. Follow-up is vital to identify any long-term potential benefits and serious adverse effects.Future workLong-term follow-up to at least 6 years after surgery is ongoing to identify recurrence rates, need for further prolapse surgery, adverse effects and cost-effectiveness.TriaI registrationCurrent Controlled Trials ISRCTN60695184.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 95. See the NIHR Journals Library website for further project information.