A culture model to analyze the acute biomaterial-dependent reaction of human primary neutrophils in vitro.

Neutrophils play a pivotal role in orchestrating the immune system response to biomaterials, the onset and resolution of chronic inflammation, and macrophage polarization. However, the neutrophil response to biomaterials and the consequent impact on tissue engineering approaches is still scarcely understood. Here, we report an in vitro culture model that comprehensively describes the most important neutrophil functions in the light of tissue repair. We isolated human primary neutrophils from peripheral blood and exposed them to a panel of hard, soft, naturally- and synthetically-derived materials. The overall trend showed increased neutrophil survival on naturally derived constructs, together with higher oxidative burst, decreased myeloperoxidase and neutrophil elastase and decreased cytokine secretion compared to neutrophils on synthetic materials. The culture model is a step to better understand the immune modulation elicited by biomaterials. Further studies are needed to correlate the neutrophil response to tissue healing and to elucidate the mechanism triggering the cell response and their consequences in determining inflammation onset and resolution.

Evaluation of natural gum-based cryogels for soft tissue engineering.

In this study, three natural biomaterials, Locust bean gum (LBG), Xanthan gum (XG), and Mastic gum (MG), were combined to form cryogel scaffolds. Thermal and chemical characterizations revealed the successful blend formation from LBG-XG (LX) and LBG-XG-MG (LXM) polymers. All blends resulted in macro-porous scaffolds with interconnected pore structures under the size of 400 µm. The swollen cryogels had similar mechanical properties compared with other polysaccharide-based cryogels. The mean tensile and compressive modulus values of the wet cryogels were in the range of 3.5-11.6 kPa and 82-398 kPa, respectively. The sustained release of the small molecule Kartogenin from varying concentrations and ratios of cryogels was in between 32 and 66% through 21 days of incubation. Physical, mechanical, and chemical properties make LX and LXM polysaccharide-based cryogels promising candidates for cartilage and other soft tissue engineering, and drug delivery applications.

3D printed poly(ε-caprolactone) scaffolds modified with hydroxyapatite and poly(propylene fumarate) and their effects on the healing of rabbit femur defects.

A large variety of approaches have been used to treat large and irregular shaped bone defects with less than optimal success due to material or design issues. In recent years patient specific constructs prepared by additive manufacturing provided a solution to the need for shaping implants to fit irregular defects in the surgery theater. In this study, cylindrical disks of poly(ε-caprolactone) (PCL) were printed by fused deposition modeling and modified with nanohydroxyapatite (HAp) and poly(propylene fumarate) (PPF) to create a mechanically strong implant with well-defined pore size and porosity, controllable surface hydrophilicity (with PPF) and osteoconductivity (with HAp). Cytotoxicity, irritation and inflammation tests demonstrated that the scaffolds were biocompatible. PCL/HAp and PCL/HAp/PPF scaffolds were implanted in the femurs of rabbits with and without seeding with rabbit Bone Marrow Stem Cells (BMSC) and examined after 4 and 8 weeks with micro-CT, mechanically and histologically. BMSC seeded PCL/HAp/PPF scaffolds showed improved tissue regeneration as determined by bone mineral density and micro-CT. Compressive and tension stiffness values (394 and 463 N mm-1) were significantly higher than those of the healthy rabbit femur (316 and 392 N mm-1, respectively) after 8 weeks of implantation. These 3D implants have great potential for patient-specific bone defect treatments.