The cell recognition of bioactive ligands immobilized on polymeric surfaces is strongly dependent on ligand presentation at the cell/material interface. While small peptide sequences such as Arg-Gly-Asp (RGD) are being widely used to obtain biomimetic interfaces, surface characteristics after immobilization as well as presentation of such ligands to cell receptors deserve more detailed investigation. Here, we immobilized an RGD-based sequence on poly(epsilon-caprolactone) (PCL), a largely widespread polymeric material used in biomedical applications, after polymer aminolysis. The surface characteristics along with the efficacy of the functionalization was monitored by surface analysis (FTIR-ATR, contact angle measurements, surface free energy determination) and spectrophotometric assays specially adapted for the analytical quantification of functional groups and/or peptides at the interface. Particular attention was paid to the evaluation of a number, morphology, and penetration depth of immobilized functional groups and/or peptides engrafted on polymeric substrates. In particular, a typical morphology in peptide distribution was evidenced on the surface raised from polymer crystallites, while a significant penetration depth of the engrafted molecules was revealed. NIH3T3 fibroblast adhesion studies verified the correct presentation of the ligand with enhanced cell attachment after peptide conjugation. Such work proposes a morphological and analytical approach in surface characterization to study the surface treatment and the distribution of ligands immobilized on polymeric substrates.

The design of porous scaffolds able to promote and guide cell proliferation, colonization, and biosynthesis in three dimensions is key determinant in bone tissue engineering (bTE). The aim of this study was to assess the role of the micro-architecture of poly(epsilon-caprolactone) scaffolds in affecting human mesenchymal stem cells' (hMSCs) spatial organization, proliferation, and osteogenic differentiation in vitro. Poly(epsilon-caprolactone) scaffolds for bTE and characterized by mono-modal and bi-modal pore size distributions were prepared by the combination of gas foaming and selective polymer extraction from co-continuous blends. The topological properties of the pore structure of the scaffolds were analyzed and the results correlated with the ability of hMSCs to proliferate, infiltrate, and differentiate in vitro in three dimensions. Results showed that the micro-architecture of the pore structure of the scaffolds plays a crucial role in defining cell seeding efficiency as well as hMSCs' three-dimensional colonization, proliferation, and osteogenic differentiation. Taken all together, our results indicated that process technologies able to allow a fine-tune of the topological properties of biodegradable porous scaffolds are essential for bTE strategies.

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Purpose In a phase II trial, SWOG S0108, patients with relapsed, aggressive non-Hodgkin lymphoma were treated with single agent bevacizumab. The primary endpoint was 6 month progression free survival (PFS) with secondary endpoints including response rate, toxicity, and laboratory correlative studies. Patients and Methods 52 patients in first or second relapse with diffuse large B-cell or mantle cell lymphoma were enrolled. 45 patients were eligible. Patients were treated with bevacizumab at 10mg/kg every 2 weeks with disease assessments every 8 weeks. Biomarkers analyzed included plasma VCAM, urine VEGF, circulating endothelial cells (CEC), and VEGF and VEGF receptor expression in lymphoma specimens. Results Therapy was well tolerated with no unexpected toxicities observed. 6 month PFS was 16% with a response rate of 2%. 11 patients had prolonged stable disease. The median duration of response or stable disease was 5.2 months (range 3.5 – 72.7). VEGF and VEGF receptor expression was observed in 70% and 65% of specimens, respectively. There was excellent concordance between expression of VEGF and VEGF receptors. Baseline urine VEGF and VCAM levels correlated with survival. CEC levels decreased in patients with elevated baseline values. Conclusion Bevacizumab, as a single agent, is well-tolerated in patients with relapsed aggressive NHL, but has little single agent activity. Laboratory correlative studies and prolonged PFS in several patients suggest the VEGF pathway may play an important role in aggressive NHL. Future trials should test the hypothesis that antiangiogenic therapies will synergize with chemotherapy regimens in improving response rates and overall survival of patients with aggressive NHL.