An off-the-shelf decellularized and sterilized human bone-ACL-bone allograft for anterior cruciate ligament reconstruction.

Approximately 1% of active individuals participating in sports rupture their anterior cruciate ligaments (ACL) every year, which is currently reconstructed using tendon autografts. Upon reconstruction, clinical issues of concern are ACL graft rupture, persistent knee instability, limited return to sports, and early onset of osteoarthritis (OA). This happens because tendon autografts do not have the same compositional, structural, and mechanical properties as a native ACL. To overcome these problems, we propose to use decellularized bone-ACL-bone allografts in ACL reconstruction (ACLR) as a mechanically robust, biocompatible, and immunologically safe alternative to autografts. Here, a decellularization protocol combined with sterilization using supercritical carbon dioxide (scCO2) was used to thoroughly decellularize porcine and human ACLs attached to tibial and femoral bone blocks. The specimens were named ultrACLean and their compositional, structural, and mechanical properties were determined. Our results indicate that: 1) decellularization of ultrACLean allografts leads to the removal of nearly 97% of donor cells, 2) ultrACLean has mechanical properties which are not different to native ACL, 3) ultrACLean maintained similar collagen content and decreased GAG content compared to native ACL, and 4) ultrACLean is not cytotoxic to seeded tendon-derived cells in vitro. Results from an in vivo pilot experiment showed that ultrACLean is biocompatible and elicits a moderate immunological response. In summary, ultrACLean has proven to be a mechanically competent and biocompatible graft with the potential to be used in ACLR surgery.

Identifying potential patient-specific predictors for anterior cruciate ligament reconstruction outcome - a diagnostic in vitro tissue remodeling platform.

PURPOSE: Upon anterior cruciate ligament (ACL) rupture, reconstruction is often required, with the hamstring tendon autograft as most widely used treatment. Post-operative autograft remodeling enhances graft rupture risk, which occurs in up to 10% of the patient population, increasing up to 30% of patients aged under 20 years. Therefore, this research aimed to identify potential biological predictors for graft rupture, derived from patient-specific tissue remodeling-related cell properties in an in vitro micro-tissue platform. METHODS: Hamstring tendon-derived cells were obtained from remnant autograft tissue after ACL reconstructions (36 patients, aged 12-55 years), and seeded in collagen I gels on a micro-tissue platform. Micro-tissue compaction over time - induced by altering the boundary constraints - was monitored. Pro-collagen I expression was assessed using ELISA, and protein expression of tenomodulin and α-smooth muscle actin were measured using Western blot. Expression and activity of matrix metalloproteinase 2 were determined using gelatin zymography. RESULTS: Only micro-tissues corresponding to younger patients occasionally released themselves from the constraining posts. Pro-collagen I expression was significantly higher in younger patients. Differences in α-smooth muscle actin and tenomodulin expression between patients were found, but these were age-independent. Active matrix metalloproteinase 2 expression was slightly more abundant in younger patients. CONCLUSIONS: The presented micro-tissue platform exposed patient-specific remodeling-related differences between tendon-derived cells, with the micro-tissues that released from constraining posts and pro-collagen I expression best reflecting the clinical age-dependency of graft rupture. These properties can be the starting point in the quest for potential predictors for identifying individual patients at risk for graft rupture.

Assessment of Graft Maturity After Anterior Cruciate Ligament Reconstruction Using Autografts: A Systematic Review of Biopsy and Magnetic Resonance Imaging studies.

PURPOSE: The purpose of this investigation was to evaluate systematically the literature concerning biopsy, MRI signal to noise quotient (SNQ) and clinical outcomes in graft-maturity assessment after autograft anterior cruciate ligament reconstruction (ACLR) and their possible relationships. METHODS: The systematic review was reported and conducted according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Studies through May 2019 evaluating methods of intra-articular ACL autograft maturity assessment were considered for inclusion. Eligible methods were histologic studies of biopsy specimens and conventional MRI studies reporting serial SNQ and/or correlation with clinical parameters. RESULTS: Ten biopsy studies and 13 imaging studies, with a total of 706 patients, met the inclusion criteria. Biopsy studies show that graft remodeling undergoes an early healing phase, a phase of remodeling or proliferation and a ligamentization phase as an ongoing process even 1 year after surgery. Imaging studies showed an initial increase in SNQ, peaking at approximately 6 months, followed by a gradual decrease over time. There is no evident correlation between graft SNQ and knee stability outcome scores at the short- and long-term follow-up after ACLR. CONCLUSIONS: The remodeling of the graft is an ongoing process even 1 year after ACLR, based on human biopsy studies. MRI SNQ peaked at approximately 6 months, followed by a gradual decrease over time. Heterogeneity of the MRI methods and technical restrictions used in the current literature limit prediction of graft maturity and clinical and functional outcome measures by means of MRI graft SNQ after ACLR. LEVEL OF EVIDENCE: Level IV, systematic review, including level III and IV studies.

Outcomes in chevron osteotomy for Hallux Valgus in a large cohort.

Clinical and radiological related outcomes have been reported for Chevron osteotomy as correction for mild to moderate hallux valgus, but only for relatively small patient series. Moreover, evaluation of the patient's point of view has mostly been conducted by means of more physician-based outcome measures. The goal of this study was to evaluate the effect of the Chevron osteotomy for hallux valgus on patients' daily lives using the Foot and Ankle Outcome Score (FAOS) as a validated and a hallux valgus specific patient reported outcome measure (PROM). Secondary outcome measures were radiological correction, complication rate, and re-operations. All 438 Chevron procedures (336 patients), at two surgical hospital sites in the period between January 2010 and October 2014, were retrospectively evaluated with a follow-up of at least 6 months. Patients were invited to fill in a cross-sectional online FAOS. For the FAOS, a total response of 60% was achieved. The FAOS ranged between 71 and 88 with a follow-up of on average 36 months. Patients with an undercorrection of their hallux valgus (11.6% of the procedures) scored significantly lower on three subscales of the FAOS (range between 61 and 77 versus 72-84). Patients who had a reoperation (12.6% of the procedures) also scored significantly lower on four subscales: 58-100 versus 73-89. Postoperative radiological measurements improved significantly with a mean difference of 6.1 (5.9; 6.4) degrees for the intermetatarsal angle and 13.7 (13.0; 14.5) degrees for the hallux valgus angle. In this large study cohort, Chevron osteotomy for hallux valgus offers good PROM scores on FAOS. These scores were significantly lower in patients with radiological undercorrection or with a reoperation. Results of the FAOS appear to modulate with physician based outcomes and therapeutic incidents. Improvement of outcome may therefore well be possible by increased attention on these surgical details.