Radially and Axially Graded Multizonal Bone Graft Substitutes Targeting Critical-Sized Bone Defects from Polycaprolactone/Hydroxyapatite/Tricalcium Phosphate

Abstract

Repair and regeneration of critical sized defects via the utilization of polymeric bone graft substitutes are challenges. Here, we introduce radially and axially graded multizonal bone graft substitutes fabricated from polycaprolactone (PCL), and PCL biocomposites with osteoconductive particles, that is, hydroxyapatite (HA), and β-tricalcium phosphate (TCP). The novel bone graft substitutes should provide a greater degree of freedom to the orthopedic surgeon especially for repair of critically sized bone defects. The modulus of the graft substitute could be tailored in the axial direction upon the systematic variation of the HA/TCP concentration, while in the radial direction the bone graft substitute consisted of an outer layer with high stiffness, encapsulating a softer core with greater porosity. The biocompatibility of the bone graft substitutes was investigated using in vitro culturing of human bone marrow-derived stromal cells followed by the analysis of cell proliferation and differentiation rates. The characterization of the tissue constructs included the enzymatic alkaline phosphates (ALP) activity, microcomputed tomography imaging, and polymerase chain reaction analysis involving the expressions of bone markers, that is, Runx2, ALP, collagen type I, osteopontin, and osteocalcin, overall demonstrating the differentiation of bone marrow derived stem cells (BMSCs) via osteogenic lineage and formation of mineralized bone tissue.

Three-dimensional printed polycaprolactone-based scaffolds provide an advantageous environment for osteogenic differentiation of human adipose-derived stem cells

“…However, objective data analysis is hampered by the multiplicity of experimental variables among different studies. First of all, PCL‐CaP composites taken for research contain different forms of CaP, namely TCP (Berner et al ., ; Polini et al ., ; Rai et al ., ), HA (Causa et al ., ; Osathanon et al ., ; Polini et al ., ) and biphasic CaP (BCP) (Ergun et al ., ; Patlolla and Arinzeh ; Shin et al ., ) have been studied. Furthermore, the very different concentrations of CaP in the scaffolds are reported in various studies in the range from 2% (Polini et al ., ) to 32% (Causa et al ., ).…”

“…It has a long biodegradation rate in vivo (Middleton and Tipton ) and can be used to manufacture porous scaffolds in custom‐made shapes to fill a particular bone defect (Woodruff and Hutmacher ). PCL‐based composites containing calcium phosphates (PCL/TCP) have also been developed (Lam et al ., ), and there is some evidence that calcium phosphates (CaPs) additives may improve the osteogenic capacity of PCL‐based scaffolds (Causa et al ., ; Ergun et al ., ; Polini et al ., ; Shin et al ., ).…”

Laminin Functionalized Biomimetic Nanofibers for Nerve Tissue Engineering

“…45,46,47, 48, 49 Such scaffolds can be graded, i.e., tailored for distributions of topographical and biochemical cues for enhancement of nerve regeneration and will be the subject of our future investigations.…”

Guided differentiation of bone marrow stromal cells on co-cultured cartilage and bone scaffolds

“…This resistance to mechanical stresses is due to the unique alignment of collagen type II fibrils in tension. [20][21][22] Biodegradable polyester PCL commonly used in many biomedical applications has good biodegradability and processability, and it does not degrade into acidic byproducts thus avoiding any inflammatory response, unlike some other polyesters. 15 Another reason for failure is the potential for delamination of the tissue due to incomplete integration with the subchondral bone.…”

“…17,[21][22][23][24][25] In the cartilage region, chondrogenesis should be associated with increased gene expression in aggrecan, Sox-9, and collagen type II. 17,[21][22][23][24][25] In the cartilage region, chondrogenesis should be associated with increased gene expression in aggrecan, Sox-9, and collagen type II.…”