Nanofiber-permeated, hybrid polymer/ceramic scaffolds for guided cell behavior

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Nanofiber-permeated, hybrid polymer/ceramic scaffolds for guided cell behavior Clarke Nelson1, Yusuf Khan1,2,3, Cato T. Laurencin1,2,3 1

Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, Institute for Regenerative Engineering, University of Connecticut Health Center, Farmington, Connecticut 2 Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT 3 Department of Chemical, Materials & Biomolecular Engineering, University of Connecticut, Storrs, CT Abstract The current gold-standard therapeutic strategies for bone grafts in the patient population are to use either allograft or autograft bone. Although these approaches have a long track record of utilization, neither is without risk to the patient, and there remains a desire in the field to improve treatment options. While there have been treatments approved by the FDA for full length growth factors and calcium salt-laden collagen sponges, these are not available for the entire population of potential bone graft patients. One viable strategy to focus on these concerns is to design an implantable bone graft substitute that can address all the negative drawbacks of autograft bone, allograft bone, and full length proteins. The work provides a preliminary investigation of synthetic, nanofiber-permeated, composite polymer/ceramic scaffold for bone repair using thermally induced phase separation, PLLA microspheres, and hydroxyapatite. The scaffolds as described have fiber diameters that mimic natural collagen ECM networks in bone as determined by scanning electron microscopy and will serve as the basis for future studies in substrate-guided bone tissue regeneration. Introduction To address the worldwide demand for bone graft substitutes, scientists from divergent backgrounds have created synthetic bone graft substitutes in an attempt to advance the field. The field has been slow to find a suitable replacement for bone grafts because the organ performs a several distinct functions: structural support, ion storage, hematopoiesis, and mounting a competent immune response.[1-4] Attempting to design implants that serve only a subset of these critical tasks, such as structural integrity, without ensuring the success of other roles, such as allowing for the creation of functional marrow space, may limit success of the implants in subsequent in vivo studies. The key to a successful next generation bone graft substitute will require more intimate control over cell-cell, cell-matrix, and cell-surface reactions. One scaffold design with an extensive research background for bone tissue engineering is the sintered microsphere scaffold. Matrices made of sintered microspheres based on degradable synthetic polymers have demonstrated the ability to act as a mechanically stable, bioresorbable, and osteoconductive scaffolds.[5] Sintered microsphere matrices based on polymers belonging to the poly(alpha hydroxyl esters) class have been widely investigated and are promising for bone tissue engineering based on t