The use of bone scaffolds to replace injured or diseased bone has many advantages over the currently used autologous and allogeneic options in clinical practice. This systematic review evaluates the current evidence for non-cellular scaffolds containing bioactive glass on osteogenesis and angiogenesis in animal bone defect models. Studies that reported results of osteogenesis via micro-CT and results of angiogenesis via Microfil perfusion or immunohistochemistry were included in the review. A literature search of PubMed, EMBASE and Scopus was carried out in November 2019 from which nine studies met the inclusion and exclusion criteria. Despite the significant heterogeneity in the composition of the scaffolds used in each study, it could be concluded that scaffolds containing bioactive glass improve bone regeneration in these models, both by osteogenic and angiogenic measures. Incorporation of additional elements into the glass network, using additives, and using biochemical factors generally had a beneficial effect. Comparing the different compositions of non-cellular bioactive glass containing scaffolds is however difficult due to the heterogeneity in bioactive glass compositions, fabrication methods and biochemical additives used.

Five studies in this review used cultured ADMSCs, while four studies used stromal vascular fraction and three used micro-fragmented adipose tissue to deliver ADMSCs. No studies reported serious treatment-related adverse effects and all reported improvements in clinical measures for at least one dose. This was not necessarily reflected in imaging evaluations nor were improvements always maintained. Current low-level evidence is limited due to variability in study methodology but indicates that treatments containing ADMSCs, when used in isolation, are safe and have the potential to reduce pain and improve function. Randomized controlled trials are now needed.

The aim of this PRISMA review was to assess whether the CMI and Actifit scaffolds, when used in clinical practice, improve clinical outcomes and demonstrate the ideal biological and biomechanical properties of scaffolds: being chondroprotective, porous, resorbable, able to mature and promote regeneration of tissue. This was done by only including studies that assessed clinical outcome and used a scale to assess both integrity of the scaffold and its effects on articular cartilage via MRI. A search was performed on PubMed, EMBASE, Scopus and clinicaltrials.gov. 2457 articles were screened, from which eight studies were selected: four used Actifit, three used CMI and one compared the two. All studies reported significant improvement in at least one clinical outcome compared to baseline. Some studies suggested that the scaffolds appeared to show porosity, mature, resorb and/or have possible chondroprotective effects, as assessed by MRI. The evidence for clinical translation is limited by differences in study methodology and small sample sizes, but is promising in terms of improving clinical outcomes in the short to mid-term. Higher level evidence, with MRI and histological evaluation of the scaffold and articular cartilage, is now needed to further determine whether these scaffolds exhibit these useful properties.

Background Quantitative magnetic resonance imaging (MRI) methods such as T1rho and T2 mapping are sensitive to changes in tissue composition, however their use in cruciate ligament assessment has been limited to studies of asymptomatic populations or patients with posterior cruciate ligament tears only. The aim of this preliminary study was to compare T1rho and T2 relaxation times of the anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) between subjects with mild-to-moderate knee osteoarthritis (OA) and healthy controls. Methods A single knee of 15 patients with mild-to-moderate knee OA (Kellgren-Lawrence grades 2–3) and of 6 age-matched controls was imaged using a 3.0 T MRI. Three-dimensional (3D) fat-saturated spoiled gradient recalled-echo images were acquired for morphological assessment and T1ρ- and T2-prepared pseudo-steady-state 3D fast spin echo images for compositional assessment of the cruciate ligaments. Manual segmentation of whole ACL and PCL, as well as proximal / middle / distal thirds of both ligaments was carried out by two readers using ITK-SNAP and mean relaxation times were recorded. Variation between thirds of the ligament were assessed using repeated measures ANOVAs and differences in these variations between groups using a Kruskal-Wallis test. Inter- and intra-rater reliability were assessed using intraclass correlation coefficients (ICCs). Results In OA knees, both T1rho and T2 values were significantly higher in the distal ACL when compared to the rest of the ligament with the greatest differences in T1rho (e.g. distal mean = 54.5 ms, proximal = 47.0 ms, p < 0.001). The variation of T2 values within the PCL was lower in OA knees (OA: distal vs middle vs proximal mean = 28.5 ms vs 29.1 ms vs 28.7 ms, p = 0.748; Control: distal vs middle vs proximal mean = 26.4 ms vs 32.7 ms vs 33.3 ms, p = 0.009). ICCs were excellent for the majority of variables. Conclusion T1rho and T2 mapping of the cruciate ligaments is feasible and reliable. Changes within ligaments associated with OA may not be homogeneous. This study is an important step forward in developing a non-invasive, radiological biomarker to assess the ligaments in diseased human populations in-vivo.