Matrix-Induced Autologous Chondrocyte Implantation (MACI) is Largely Effective and Provides Significant Improvement in Patients With Symptomatic, Large Chondral Defects: A Systematic Review and Meta-Analysis.

INTRODUCTION: The purpose of this study was to perform a meta-analysis for long-term patient-reported outcome (PRO) measures in Matrix-induced Autologous Chondrocyte Implantation (MACI) patients using the Knee Injury and Osteoarthritis Outcome Score (KOOS) model. MATERIALS AND METHODS: A literature search under the PubMed/Medline and Embase databases was conducted. Statistical significance was determined between the mean pre- and postoperative scores at each time point (1-, 2-, and 5-years). Cohen's d analysis was used to measure the effect size (ES) in each group when compared to preoperative measurements to determine clinical responsiveness. RESULTS: KOOS subscales at all long-term postoperative follow ups measured in this study showed significant (p-value < 0.001) improvement when compared to preoperative scores. Furthermore, apart from KOOS sports and recreation (KOOS-SR) at 1-year postoperative follow up that showed a medium ES (ES, 0.761), all other KOOS subscales at long-term follow up periods showed a large (>0.8) ES on mean preoperative KOOS. CONCLUSION: Review of the literature demonstrate an absence of large meta-analyses for long-term PRO measures with the MACI procedure. It was found that all subscales were largely responsive when evaluated at >2 years after surgery. Based on these results, MACI is an effective treatment option for patients with symptomatic, full-thickness cartilage defects about the knee.

Salt-bridging effects on short amphiphilic helical structure and introducing sequence-based short beta-turn motifs.

Determining the minimal sequence necessary to induce protein folding is beneficial in understanding the role of protein-protein interactions in biological systems, as their three-dimensional structures often dictate their activity. Proteins are generally comprised of discrete secondary structures, from α-helices to ß-turns and larger ß-sheets, each of which is influenced by its primary structure. Manipulating the sequence of short, moderately helical peptides can help elucidate the influences on folding. We created two new scaffolds based on a modestly helical eight-residue peptide, PT3, we previously published. Using circular dichroism (CD) spectroscopy and changing the possible salt-bridging residues to new combinations of Lys, Arg, Glu, and Asp, we found that our most helical improvements came from the Arg-Glu combination, whereas the Lys-Asp was not significantly different from the Lys-Glu of the parent scaffold, PT3. The marked 310-helical contributions in PT3 were lessened in the Arg-Glu-containing peptide with the beginning of cooperative unfolding seen through a thermal denaturation. However, a unique and unexpected signature was seen for the denaturation of the Lys-Asp peptide which could help elucidate the stages of folding between the 310 and α-helix. In addition, we developed a short six-residue peptide with ß-turn/sheet CD signature, again to help study minimal sequences needed for folding. Overall, the results indicate that improvements made to short peptide scaffolds by fine-tuning the salt-bridging residues can enhance scaffold structure. Likewise, with the results from the new, short ß-turn motif, these can help impact future peptidomimetic designs in creating biologically useful, short, structured ß-sheet-forming peptides.

Cryo-EM maps reveal five-fold channel structures and their modification by gatekeeper mutations in the parvovirus minute virus of mice (MVM) capsid.

In minute virus of mice (MVM) capsids, icosahedral five-fold channels serve as portals mediating genome packaging, genome release, and the phased extrusion of viral peptides. Previous studies suggest that residues L172 and V40 are essential for channel function. The structures of MVMi wildtype, and mutant L172T and V40A virus-like particles (VLPs) were solved from cryo-EM data. Two constriction points, termed the mid-gate and inner-gate, were observed in the channels of wildtype particles, involving residues L172 and V40 respectively. While the mid-gate of V40A VLPs appeared normal, in L172T adjacent channel walls were altered, and in both mutants there was major disruption of the inner-gate, demonstrating that direct L172:V40 bonding is essential for its structural integrity. In wildtype particles, residues from the N-termini of VP2 map into claw-like densities positioned below the channel opening, which become disordered in the mutants, implicating both L172 and V40 in the organization of VP2 N-termini.