In this study, poly(ε-caprolactone)/poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PCL/PHBV) blended porous scaffolds were fabricated by fused deposition modeling (FDM). PCL/PHBV filaments, initially prepared at different weight ratios, that is, 100/0, 75/25, 50/50, and 25/75, were fabricated by the lay-down pattern of 0/90/45/135° to obtain scaffolds with dimension of 6.0 × 6.0 × 2.5 mm and average filament diameters and channel sizes in the ranges of 370-390 µm and 190-210 µm, respectively. To enhance the surface hydrophilicity of the materials, the scaffolds were subsequently subjected to a low pressure oxygen plasma treatment. The untreated and plasma-treated scaffolds were comparatively characterized, in terms of surface properties, mechanical strength, and biological properties. From SEM, AFM, water contact angle, and XPS results, the surface roughness, wettability, and hydrophilicity of the blended scaffolds were found to be enhanced after plasma treatment, while the compressive strength of the scaffolds was scarcely changed. It was, however, found to increase with an increasing content of PHBV incorporated. The porcine chondrocytes exhibited higher proliferative capacity and chondrogenic potential when being cultured on the scaffolds with greater PHBV contents, especially when they were plasma-treated. The PCL/PHBV scaffolds were proven to possess good physical, mechanical, and biological properties that could be appropriately used in articular cartilage regeneration. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1141-1150, 2017.

Conventional treatment of jaw bone infection is often ineffective at controlling bacterial infection and enhancing bone regeneration. Biodegradable composite hydrogels comprised of carboxymethyl chitosan (CMCS) and clindamycin (CDM)-loaded mesoporous silica nanoparticles (MCM-41), possessing dual antibacterial activity and osteogenic potency, were developed in the present study. CDM was successfully loaded into both untreated and plasma-treated MCM-41 nanoparticles, denoted as (p)-MCM-41, followed by the incorporation of each of CDM-loaded (p)-MCM-41 into CMCS. The resulting CDM-loaded composite hydrogels, (p)-MCM-41-CDM-CMCS, demonstrated slow degradation rates (about 70% remaining weight after 14-day immersion), while the CDM-free composite hydrogel entirely disintegrated after 4-day immersion. The plasma treatment was found to improve drug loading capacity and slow down initial drug burst effect. The prolonged releases of CDM from both (p)-MCM-41-CDM-CMCS retained their antibacterial effect against Streptococcus sanguinis for at least 14 days in vitro. In vitro assessment of osteogenic activity showed that the CDM-incorporated composite hydrogel was cytocompatible to human mesenchymal stem cells (hMSCs) and induced hMSC mineralization via p38-dependent upregulated alkaline phosphatase activity. In conclusion, novel (p)-MCM-41-CDM-CMCS hydrogels with combined controlled release of CDM and osteogenic potency were successfully developed for the first time, suggesting their potential clinical benefit for treatment of intraoral bone infection.

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Extensive desmoplasia in cholangiocarcinoma (CCA) is associated with tumor aggressiveness, indicating a need for further understanding of CCA cell-matrix interaction. This study demonstrated laminin as the most potent attractant for CCA cell migration and the vast elevation of its receptor integrin β4 (ITGB4) in CCA cell lines. Besides, their high expressions in CCA tissues were correlated with lymphatic invasion and the presence of ITGB4 was also associated with short survival time. ITGB4 silencing revealed it as the receptor for laminin-induced HuCCA-1 migration, but KKU-213 utilized 37/67-kDa laminin receptor (LAMR) instead. These findings highlight the role of ITGB4 and LAMR in transducing laminin induction of CCA cell migration and the potential of ITGB4 as diagnostic and prognostic biomarkers for CCA.

Enhancement of porcine chondrocyte growth, distribution and functions within polycaprolactone (PCL) scaffolds was attempted using alkaline hydrolysis and oxygen plasma treatment. The hydrolysis of PCL was performed either before or after scaffold fabrication in the preparations of pre-hydrolyzed PCL (pre-HPCL) or post-HPCL scaffolds, respectively. The PCL, pre-HPCL, and post-HPCL scaffolds were subsequently plasma-treated to yield plasma-treated PCL, plasma-treated pre-HPCL, and plasma-treated post-HPCL scaffolds, respectively. All scaffolds were comparatively characterized, in terms of surface morphology, hydrophilicity, and atomic composition using scanning electron microscopy, contact angle measurement and X-ray photoelectron spectroscopy, respectively. The interactions of chondrocytes with individual scaffolds were assessed, in terms of cartilage-gene expression and cartilaginous matrix production using reverse transcription polymerase chain reaction analysis and glycosaminoglycans (GAGs) assay, respectively. The cell infiltration and cartilaginous matrix distribution were investigated by histological and immunofluorescence analysis. The results revealed that the plasma treatment exhibited a more prominent effect on the enhancement of surface roughness and hydrophilicity of the scaffolds than the alkaline hydrolysis. The scaffolds subjected to both surface treatments stimulated the cells to secret more GAGs and type II collagen. The sequence of hydrolysis of PCL also evidently played a crucial role in the hydrophilicity of the materials and the cartilage-gene expression and cartilaginous matrix production of the cultured chondrocytes. The hydrolysis of PCL prior to the fabrication, followed by the oxygen plasma treatment of the resulting fabricated scaffold, yielded plasma-treated pre-HPCL scaffold with homogeneous hydrophilic characteristics all over the material. Consequently, the cells could proliferate well, infiltrate most deeply and ultimately produce the highest amounts of the cartilage-specific substances throughout this scaffold.

The major concern related to biodegradable bone substitute materials is the loss of mechanical strength which can be undesirable when occurring too quickly before new bone formation. In this study, the multifunctional lactide oligomers having 2, 3, and 4 arms end capped with methacrylate groups were synthesized with the aim of improving the degradation properties. Their composites with hydroxyapatite (HA) were photopolymerized and subjected to accelerated degradation at 60 °C. The results showed that increasing number of arms significantly improved thermal and mechanical properties as well as biocompatibility of the composites. All composites although varying in number of arms had similar levels of bone-specific gene expression and calcification indicating their equal bioactivity in supporting bone formation. The high HA content in the composites was proposed to be responsible for enhanced osteoblast response, and this tended to suppress the effects of polymeric structure.

Bone morphogenic protein-2 (BMP-2) knuckle epitope peptide has been recently discovered and known to activate chondrogenesis. However, the applications of this soluble peptide remain very limited due to rapid diffusion resulting in poor cellular uptake into target cells. We herein designed nanoparticles made from hyaluronic acid functionalized gold nanorods (GNRs) to conjugate with thiolated BMP-2 knuckle epitope peptide via a two-step reaction. Hyaluronic acid was modified to have thiol functional groups to replace the cetyl trimethylammonium bromide ligands on the surface of GNRs. The thiolated peptides were subsequently reacted with hyaluronic acid on the surface on GNRs via a maleimide-hydrazide crosslinker. The conjugation was confirmed by the change of surface charge of GNRs and the plasmon shift. A colorimetric peptide assay suggested more than 69% of the thiolated peptides were conjugated with the hyaluronic acid coated gold nanorods. Moreover, in vitro cell viability showed that BMP-2 conjugated hyaluronic acid functionalized gold nanorods (B2HGR) were cytocompatible and did not cause cytotoxicity to fibroblast cells. The B2HGRs also significantly promote cellular uptake of the BMP-2 peptides in both human mesenchymal stem cells and porcine chondrocytes due to multivalent ligand binding to the BMP receptors on the cell surface resulting in receptor-mediated endocytosis. The enhanced cellular uptake was clearly observed under a confocal microscope resulting in the significant activation of type II collagen gene expression and glucosaminoglycan secretion in those cells. Furthermore, our delivery system is a proof-of-concept of using scaffolds in combination with nanodelivery platform to enhance cartilaginous repair. The peptide loading capacity and the release is not limited by the scaffolds. Therefore, our delivery platform has potential applications for cartilage regeneration in a preclinical and clinical setting in the future.