In vitro and in vivo biocompatibility assessment of free radical scavenging nanocomposite scaffolds for bone tissue regeneration.

Bone is the second most transplanted tissue in the world, resulting in increased demand for bone grafts leading to the fabrication of synthetic scaffold grafting alternatives. Fracture sites are under increased oxidative stress after injuries, affecting osteoblast function and hindering fracture healing and remodeling. To counter oxidative stress, free radical scavenging agents, such as cerium oxide nanoparticles, have gained traction in tissue engineering. Toward the goal of developing a functional synthetic system for bone tissue engineering, we characterized the biocompatibility of a porous, bioactive, free radical scavenging nanocomposite scaffold composed of poly(1,8 octanediol-co-citrate), beta-tricalcium phosphate, and cerium oxide nanoparticles. We studied cellular and tissue compatibility utilizing in vitro and in vivo models to assess nanocomposite interactions with both human osteoblast cells and rat subcutaneous tissue. We found the scaffolds were biocompatible in both models and supported cell attachment, proliferation, mineralization, and infiltration. Using hydrogen peroxide, we simulated oxidative stress to study the protective properties of the nanocomposite scaffolds via a reduction in cytotoxicity and recovered mineralization of osteoblast cells in vitro. We also found after implantation in vivo the scaffolds exhibited biocompatible properties essential for successful scaffolds for bone tissue engineering. Cells were able to infiltrate through the scaffolds, the surrounding tissues elicited a minimal immune response, and there were signs of scaffold degradation after 30 days of implantation. After the array of biological characterization, we had confirmed the development of a nanocomposite scaffold system capable of supporting bone-remodeling processes while providing a protective free radical scavenging effect.

Multi-layer approaches to scaffold-based small diameter vessel engineering: A review.

Cardiovascular disease is one of the leading causes of death in the world. A characteristic symptom of cardiovascular disease is occlusion of vessels. Once vascular occlusion occurs there is a critical need to re-establish flow to prevent ischemia in the downstream tissues. In the most advanced cases, flow is re-established by creating a secondary flow path around the blockage, bypass grafting. For large diameter applications, synthetic conduits are successfully implanted, however in small diameter applications re-occlusion occurs and there is a critical need for new vascular grafts. There are many strategies and approaches that are being employed to design an effective and successful vascular graft. However, to date, there are no clinically available small diameter vascular grafts that are consistently successful in vivo long term (>7 years). As an effort to develop a successful graft there are several tissue engineering approaches: cell sheets, synthetic and natural biomaterial platforms, and decellularized extracellular matrices that are being investigated. While each area has its advantages, scaffold-based approaches are among the most widely studied. Scaffold based approaches are extensively studied due to tailorability and the availability of synthetic and natural polymers. Within the area of scaffold-based approaches, biomimicry has become an increasingly studied area, and structural biomimicry is one of the many approaches. The focus of this review paper is to analyze scaffold-based approaches. Particularly the advantages and disadvantages of using multi-layer scaffold-based approaches to engineer conduits for small diameter applications.

Fabrication of a bilayer scaffold for small diameter vascular applications.

One of the greatest challenges plaguing cardiovascular tissue engineering has been the development of a compliant vascular graft. In this work, we report the development of a synthetic vascular graft with compliance similar to native arteries at physiological pressures. A bilayer scaffold was fabricated from a solid polymeric lumen made from poly(1,8 octanediol-co-citrate) (POC) and a microfibrous medial layer composed of type I collagen, elastin, and POC. Mechanical analysis revealed dynamic compliance, ~6.9% within 1% of native vessels, 5.9%. The burst pressure was an order of magnitude lower than native vessels (~400 mmHg vs. ~3000 mmHg) but was above physiological pressure ranges. Biocompatibility studies indicated the scaffold posed no acute cytotoxic risk to relevant cell types and supported the proliferation of vascular smooth muscle cells. In addition, upon exposure of the scaffold to whole blood, there was no statistically significant hemolysis, <2%. Overall this is a promising material system and scaffold to develop a biodegradable tissue-engineered vascular graft. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2850-2862, 2018.

Development of poly (1,8 octanediol-co-citrate) and poly (acrylic acid) nanofibrous scaffolds for wound healing applications.

Wound care is one of the leading health care problems in the United States costing billions of dollars yearly. Annually, millions of acute wounds occur due to surgical procedures or traumas such as burns and abrasions, and these wounds can become non-healing due to bacterial infection or underlying pathologies. Current wound care treatments include the use of bioinert constructs combined with topical administration of anti-bacterial agents and growth factors. However, there is a growing need for the development of bioactive wound dressing materials that are able to promote wound healing and the regeneration of healthy tissue. In this work, we evaluate and report the use of a novel electrospun polymeric scaffold consisting of poly (1,8 octanediol-co-citrate) and poly (acrylic acid) for wound healing applications. The scaffold exhibits intrinsic antibacterial activity, hydrogel-like water uptake abilities, and the ability to deliver physiologically relevant concentrations of growth factor. Additionally, the scaffold shows antibacterial function when tested with bacteria relevant to wound healing applications. Biological characterization of the electrospun scaffold shows excellent cellular adhesion, low cytotoxicity, and enhanced proliferation of skin fibroblasts. This work has potential towards the development of novel bioactive scaffolds for prevention of bacterial infiltration into the wound bed and enhanced healing.

Biocompatible shaped particles from dried multilayer polymer capsules.

We demonstrated a simple and facile approach to fabricate biocompatible monodisperse hollow microparticles of controlled geometry. The hemispherical, spherical, and cubical microparticles are obtained by drying multilayer capsules of hydrogen-bonded poly(N-vinylpyrrolidone)/tannic acid (PVPON/TA)n. Drying spherical capsules results in hemispherical particles if 15 < n < 20. This shape transformation is controlled by capsule stiffness, which is regulated by the layer number, capsule diameter, and PVPON molecular weight. Cubical and spherical hollow particles maintaining their three-dimensional shapes in the dry state are obtained if n ≥ 25.5. A 17-fold stiffness increase is required to lead from totally collapsed (PVPON/TA)5.5 to dried self-supporting (PVPON/TA)25.5 particles of 2 µm in dimensions. All hollow particles could be further resuspended in aqueous solutions while retaining their shapes upon rehydration. The cell growth and viability studies using human cancer cells revealed noncytotoxic properties of the (PVPON/TA) multilayer particles. Both spherical and hemispherical capsules were internalized by macrophages with the uptake of the hemispherical particles per cell two times more efficient. The method presented here allows for a robust preparation of biocompatible shaped particles whose shape and dimensions can be easily tuned by controlling capsule size and wall thickness. The reported structures can be potentially useful for biomedical applications such as shape-controlled cellular uptake and flow dynamics.