Decellularized extracellular matrix biomaterials for regenerative therapies: Advances, challenges and clinical prospects.

Tissue engineering and regenerative medicine have shown potential in the repair and regeneration of tissues and organs via the use of engineered biomaterials and scaffolds. However, current constructs face limitations in replicating the intricate native microenvironment and achieving optimal regenerative capacity and functional recovery. To address these challenges, the utilization of decellularized tissues and cell-derived extracellular matrix (ECM) has emerged as a promising approach. These biocompatible and bioactive biomaterials can be engineered into porous scaffolds and grafts that mimic the structural and compositional aspects of the native tissue or organ microenvironment, both in vitro and in vivo. Bioactive dECM materials provide a unique tissue-specific microenvironment that can regulate and guide cellular processes, thereby enhancing regenerative therapies. In this review, we explore the emerging frontiers of decellularized tissue-derived and cell-derived biomaterials and bio-inks in the field of tissue engineering and regenerative medicine. We discuss the need for further improvements in decellularization methods and techniques to retain structural, biological, and physicochemical characteristics of the dECM products in a way to mimic native tissues and organs. This article underscores the potential of dECM biomaterials to stimulate in situ tissue repair through chemotactic effects for the development of growth factor and cell-free tissue engineering strategies. The article also identifies the challenges and opportunities in developing sterilization and preservation methods applicable for decellularized biomaterials and grafts and their translation into clinical products.

Bilateral Flexor Digitorum Accessorius Longus Precipitating Bilateral Tarsal Tunnel Syndrome: A Case Report.

CASE: A 29-year-old woman presented with bilateral tarsal tunnel syndrome caused by bilateral flexor digitorum accessorius longus, experiencing immediate relief of symptoms after surgical intervention through 1 year. CONCLUSION: Accessory muscles can cause compressive neuropathies in multiple areas of the body. In patients who have FDAL as the cause of their tarsal tunnel syndrome, surgeons should have a high index of suspicion of bilateral FDAL if the same patient develops similar contralateral symptoms.

Validation of the Single Assessment Numeric Evaluation (SANE) Score as an Outcome Measure by Comparison to the Revised Foot Function Index (rFFI).

BACKGROUND: Patient-reported outcome measures serve as an invaluable tool in both the clinical and research setting to monitor a patient's condition and efficacy of treatments over time. We aim to validate the Single Assessment Numeric Evaluation (SANE) score for disorders of the lower extremity using the revised-Foot Function Index (rFFI) as a reference. The SANE score is a 1-question survey that may improve efficiency of outcome data collection in the clinical setting. METHODS: Patient age, sex, visit diagnosis by ICD-10 code, SANE score, and rFFI score were collected retrospectively from 218 initial patient encounters between January 2015 through July 2017. Patients were included if they were 18 years or older and were excluded if they had incomplete SANE or rFFI data. Results of the two scores were compared using the Pearson or Spearman correlation coefficients, with correlation defined as excellent (>0.7), excellent-good (0.61-0.7), good (0.4-0.6), or poor (0.2-0.39). Diagnoses were categorized into 9 subgroups that were analyzed, including forefoot, plantar fasciitis, arthritis, deformity, fracture, tendinitis, osteochondral defect (OCD) of the talus, acute soft tissue trauma, and "other." RESULTS: The SANE score had good correlation with the overall rFFI score (r = 0.51, P < .01). When comparing the SANE score to the rFFI subscores, there was good correlation with pain (r = 0.42, P < .01), good correlation with stiffness (r = 0.44, P < .01), poor correlation with activity (r = 0.36, P <.01), good correlation with difficulty (r = 0.52, P < .01), and poor correlation with social issues (r = 0.39, P < .01). Subanalysis showed an excellent-good correlation between SANE and rFFI score for forefoot pathology (r = 0.67, P < .01) and plantar fasciitis (r = 0.63, P < .02), good correlation for arthritis (r = 0.49, P < .04), deformity (r = 0.60, P < .01), fracture (r = 0.50, P < .01), and tendinitis (r = 0.47, P < .02), and no significant correlation for OCD of the talus (r = 0.56, P < .15) and acute soft tissue trauma (r = 0.19, P < .32). CONCLUSION: The SANE score demonstrates excellent-good correlation with the rFFI for specific pathology including the forefoot and plantar fasciitis and has limited correlation with other pathology.

Osteochondral Tissue Engineering: Translational Research and Turning Research into Products.

Osteochondral (OC) defect repair is a significant clinical challenge. Osteoarthritis results in articular cartilage/subchondral bone tissue degeneration and tissue loss, which in the long run results in cartilage/ostecochondral defect formation. OC defects are commonly approached with autografts and allografts, and both these options have found limitations. Alternatively, tissue engineered strategies with biodegradable scaffolds with and without cells and growth factors have been developed. In order to approach regeneration of complex tissues such as osteochondral, advanced tissue engineered grafts including biphasic, triphasic, and gradient configurations are considered. The graft design is motivated to promote cartilage and bone layer formation with an interdigitating transitional zone (i.e., bone-cartilage interface). Some of the engineered OC grafts with autologous cells have shown promise for OC defect repair and a few of them have advanced into clinical trials. This chapter presents synthetic osteochondral designs and the progress that has been made in terms of the clinical translation.

Initial Fibular Displacement as a Predictor of Medial Clear Space Widening in Weber B Ankle Fractures.

BACKGROUND: The diagnosis of medial ankle instability in Weber B ankle fractures remains controversial. Manual stress and gravity stress radiographs as well as magnetic resonance imaging (MRI) are used, but there is no consensus gold standard. The purpose of this study was to determine the relationship between initial fibular displacement and medial clear space widening on a gravity stress radiograph as a predictor of instability. METHODS: A retrospective review was conducted of all patients with isolated Weber B ankle fractures with both initial injury radiographs and gravity stress view from August 1, 2014, through April 1, 2016. A total of 17 patients were identified. On the mortise view of initial injury radiographs, medial clear space (MCS), superior clear space, lateral fibular displacement (LFDP), and fibular shortening (FS) were measured, and on the lateral view, anterior to posterior fibular gap (A to P FG) was measured. MCS was again measured on the gravity stress view (MCS-W). Statistical analyses identified the correlations of each displacement variable relative to MCS-W as well as the sensitivity and specificity of each parameter. RESULTS: A cutoff point for MCS-W was set as less than 5.0 mm (n = 8) and 5.0 mm or more (n = 9). Strong significant correlations with MCS-W were found for A to P FG (0.84, P < .001), with a trend for LFDP (0.62, P = .008), but no significance with FS (0.38, P = .84). Linear regression analysis revealed significant ability to predict MCS-W for both LFDP ( P = .002) and A to P FG ( P = .001) but not FS. Receiver operating characteristic analysis for A to P FG using a threshold value of 1.0 mm yielded sensitivity and specificity of 100% in predicting an MCS-W of 5.0 mm or more. CONCLUSION: The initial fibular displacement was a strong predictor of MCS-W in Weber B ankle fractures. On lateral radiographs, an A to P FG greater than 1.0 mm showed a sensitivity and specificity of 100% in predicting an MCS-W of 5.0 mm or more on gravity stress view. LEVEL OF EVIDENCE: Level III case series, prognostic.

The use of intramedullary nails in tibiotalocalcaneal arthrodesis.

Tibiotalocalcaneal arthrodesis is a salvage procedure undertaken for hindfoot problems that affect both the ankle and subtalar joints (eg, two-joint arthritis, severe acute trauma, osteonecrosis of the talus, severe malalignment deformities, significant hindfoot bone loss). Methods of achieving fusion include Steinmann pins, screws, plates, external fixators, and retrograde intramedullary nailing. Retrograde intramedullary nailing provides a load-sharing fixation device with superior biomechanical properties and is an excellent choice for use in tibiotalocalcaneal arthrodesis. This technique can be performed through relatively small incisions. In addition, recent design modifications include the availability of dynamization and the choice of curved or straight nails. Contraindications to the technique include the presence of infection, severe vascular disease, and severe malalignment of the tibia.

Acute effects of the Protonics system on patellofemoral alignment: an MRI study.

This study used magnetic resonance imaging (MRI) to determine whether changes in patellofemoral alignment occur after initial treatment with the Protonics exercise device. The first scan was obtained before the device was used. After performing a set of exercises with no resistance on the device the device was removed, and a second scan was obtained. The same set of exercises was again performed with resistance on the device set at the appropriate level, and a final scan was obtained with the device removed. An isometric leg press was maintained as each image was obtained to simulate more closely a functional weight-bearing activity. Subjects were 26 women with complaints of patellofemoral pain. The main outcome measures were: patellar tilt angle, bisect offset, and lateral facet angle. Nonparametric repeated measures analysis of variance tests showed no differences between test conditions for any of the three measures of patellofemoral alignment. We conclude that after an initial treatment session using the Protonics system there is no change in patellofemoral alignment as determined by MRI.