Control of in vivo microvessel ingrowth by modulation of biomaterial local architecture and chemistry

Abstract

We developed a method for controlling local architecture and chemistry simultaneously in biomaterial implants to control microvessel ingrowth in vivo. Porous polypropylene disks (5 mm in diameter and 40 microm thick) were plasma-coated with a fluoropolymer and then laser-drilled with 50-microm-diameter holes through their thickness. We then oxidized the disks to create hydroxyl functionality on the exposed polypropylene (inside the holes). Acrylamide was grafted to the hydroxyl groups through polymerization in the presence of activating ceric ions. Staining with toluidine blue O demonstrated that grafting occurred only inside the holes. We used the Hoffman degradation reaction to convert the amide groups of acrylamide to amine groups, and then we used ethylene glycol diglycidyl ether to attach biomolecules of interest inside the holes: secreted protein acidic and rich in cysteine (SPARC) peptide Lys-Gly-His-Lys (KGHK; angiogenic), thrombospondin-2 (TSP; antiangiogenic), or albumin (rat; neutral). In vivo testing in a rat subcutaneous dorsum model for a 3-week interval demonstrated a greater vessel surface area (p = 0.032) and a greater number of vessels (p = 0.043) in tissue local to the holes with KGHK-immobilized disks than with TSP-immobilized disks. However, differences between KGHK-immobilized and albumin-immobilized disks were less significant (p = 0.120 and p = 0.289 for the vessel surface area and number of vessels, respectively). The developed methods have potential applications in biomaterial design applications for which selective neovascularization is desired.

The Influence of pH upon the Kinetic Parameters of the Enzymatic Hydrolysis of Cellobiose with Novozym 188

“…To regenerate bone tissues, the scaffold should have an appropriate pore size and 100% pore interconnectivity, so that pore structure microvascular induction can occur and osteogenesis can be maintained 29, 30. As previously reported, the optimal pore size remains an issue of debate in bone tissue regeneration.…”

In vivo cytokine-associated responses to biomaterials

“…This assessment was based on elevated macrophage, alkaline phosphatase, and acid phosphatase concentrations; however, extracellular protein concentrations did not vary significantly between the PE and ot-PVC. Other cage implant studies have shown that specimen surface chemistry impacts macrophage adhesion, FBGC fusion, apoptosis, microvessel growth, and surface protein expression in vivo [12–16]. Of greatest relevance was the study by Brodbeck et al that used the cage implant system to show that material-adherent macrophages express mRNA for cytokines and growth factors such as IL-6, IL-8, IL-10, TGF-β, IL-1β, and IL-13 in a surface chemistry dependent manner [5].…”

Multi-layered polycaprolactone–alginate–fucoidan biocomposites supplemented with controlled release of fucoidan for bone tissue regeneration: fabrication, physical properties, and cellular activities

“…23 According to several researchers, proper pore structure can result in high osteoblastic activities. 24 However, the optimal pore size of the scaffold for bone tissue regeneration has been a debated issue, because the several aspects that affect cellular behavior can be mixed; smaller pore sizes increase the surface area of scaffolds and induce high cell attachment, while larger pore sizes induce easy migration of cells. Although the optimum pore size is not well defined in bone tissue regeneration, in this work, we selected a pore size of 300 mm and square pore shape.…”