Functionalized PCL/HA nanocomposites as microporous membranes for bone regeneration.

In the present work, microporous membranes based on poly(ε-caprolactone) (PCL) and PCL functionalized with amine (PCL-DMAEA) or anhydride groups (PCL-MAGMA) were realized by solvent-non solvent phase inversion and proposed for use in Guided Tissue Regeneration (GTR). Nanowhiskers of hydroxyapatite (HA) were also incorporated in the polymer matrix to realize nanocomposite membranes. Scanning Electron Microscopy (SEM) showed improved interfacial adhesion with HA for functionalized polymers, and highlighted substantial differences in the porosity. A relationship between the developed porous structure of the membrane and the chemical nature of grafted groups was proposed. Compared to virgin PCL, hydrophilicity increases for functionalized PCL, while the addition of HA influences significantly the hydrophilic characteristics only in the case of virgin polymer. A significant increase of in vitro degradation rate was found for PCL-MAGMA based membranes, and at lower extent of PCL-DMAEA membranes. The novel materials were investigated regarding their potential as support for cell growth in bone repair using multipotent mesenchymal stromal cells (MSC) as a model. MSC plated onto the various membranes were analyzed in terms of adhesion, proliferation and osteogenic capacity that resulted to be related to chemical as well as porous structure. In particular, PCL-DMAEA and the relative nanocomposite membranes are the most promising in terms of cell-biomaterial interactions.

[1]  Development of hydroxyapatite nanorods-polycaprolactone composites and scaffolds derived from a novel in-situ sol-gel process , 2012, Tissue Engineering and Regenerative Medicine.

[2]  J. Jansen,et al.  Chitosan/bioactive glass nanoparticle composite membranes for periodontal regeneration. , 2012, Acta biomaterialia.

[3]  Xu-Ming Xie,et al.  Study of multi-monomer melt-grafting onto polypropylene in an extruder , 2000 .

[4]  M. Textor,et al.  Biodegradable polymer/hydroxyapatite composites: surface analysis and initial attachment of human osteoblasts. , 2001, Journal of biomedical materials research.

[5]  Suming Li,et al.  Synthesis and degradation of PLA–PCL–PLA triblock copolymer prepared by successive polymerization of ε-caprolactone and dl-lactide , 2004 .

[6]  E. D. Pace,et al.  Poly(ε-caprolactone) modified by functional groups: Preparation and chemical–physical investigation , 2009 .

[7]  Biqiong Chen,et al.  Mechanical and dynamic viscoelastic properties of hydroxyapatite reinforced poly(ε-caprolactone) , 2005 .

[8]  A. F. Giamei,et al.  Inhomogeneous deformation of nickel-base superalloy 〈111〉 monocrystals under compression , 1977 .

[9]  J. Vacanti,et al.  Synthetic Polymers Seeded with Chondrocytes Provide a Template for New Cartilage Formation , 1991, Plastic and reconstructive surgery.

[10]  Michel Vert,et al.  Aliphatic polyesters: great degradable polymers that cannot do everything. , 2005, Biomacromolecules.

[11]  筏 義人.  Tissue engineering : fundamentals and applications , 2006 .

[12]  M. Natu,et al.  Influence of polymer processing technique on long term degradation of poly(ε-caprolactone) constructs , 2013 .

[13]  Li Li,et al.  Structure and performance of nano-hydroxyapatite filled biodegradable poly((1,2-propanediol-sebacate)-citrate) elastomers , 2009 .

[14]  C. Simon,et al.  Strong and bioactive composites containing nano-silica-fused whiskers for bone repair. , 2004, Biomaterials.

[15]  Jidong Li,et al.  Properties and in vitro biological evaluation of nano-hydroxyapatite/chitosan membranes for bone guided regeneration , 2009 .

[16]  Changsheng Liu,et al.  Development of asymmetric gradational-changed porous chitosan membrane for guided periodontal tissue regeneration , 2007 .

[17]  D. Hutmacher,et al.  Degradation characteristics of poly(ε-caprolactone)-based copolymers and blends , 2006 .

[18]  F. Schwarz,et al.  Regeneration of periodontal tissues: combinations of barrier membranes and grafting materials - biological foundation and preclinical evidence: a systematic review. , 2008, Journal of clinical periodontology.

[19]  M. Malinconico,et al.  Synthesis and Characterization of Functionalized Crosslinkable Poly(ε‐caprolactone) , 2006 .

[20]  Wenpeng Shan,et al.  Fabrication and properties of degradable poly(amino acid)/nano hydroxyapatite bioactive composite , 2012 .

[21]  T. Webster,et al.  Osteoblast adhesion on nanophase ceramics. , 1999, Biomaterials.

[22]  Suming Li,et al.  Hydrolytic degradation of poly(DL-lactic acid) in the presence of caffeine base , 1996 .

[23]  T. Webster,et al.  Enhanced functions of osteoblasts on nanophase ceramics. , 2000, Biomaterials.

[24]  Mara Riminucci,et al.  Bone Marrow Stromal Stem Cells: Nature, Biology, and Potential Applications , 2001, Stem cells.

[25]  Xinlong Wang,et al.  Preparation and characterization of n-hydroxyapatite/PCL-pluronic-PCL nanocomposites for tissue engineering. , 2010, Journal of nanoscience and nanotechnology.

[26]  M. Mohammadi,et al.  In vitro study of hydroxyapatite/polycaprolactone (HA/PCL) nanocomposite synthesized by an in situ sol-gel process. , 2013, Materials science & engineering. C, Materials for biological applications.

[27]  D. Kaplan,et al.  Role of adult mesenchymal stem cells in bone tissue engineering applications: current status and future prospects. , 2005, Tissue engineering.

[28]  V. Soldi,et al.  Maleic Anhydride Grafting on EPDM: Qualitative and Quantitative Determination , 1999 .

[29]  A. Schindler,et al.  Aliphatic polyesters. I. The degradation of poly(ϵ‐caprolactone) in vivo , 1981 .

[30]  H. Kim,et al.  Robocasting nanocomposite scaffolds of poly(caprolactone)/hydroxyapatite incorporating modified carbon nanotubes for hard tissue reconstruction. , 2013, Journal of biomedical materials research. Part A.

[31]  Mario Malinconico,et al.  Natural and Synthetic Hydroxyapatite Filled PCL: Mechanical Properties and Biocompatibility Analysis , 2004 .

[32]  N. Kawazoe,et al.  Structural changes and biodegradation of PLLA, PCL, and PLGA sponges during in vitro incubation , 2010 .

[33]  R. Legras,et al.  The anhydride content of some commercial PP-g-MA: FTIR and titration , 1996 .

[34]  Mario Malinconico,et al.  Poly (D,L-lactic acid)/poly (∈-caprolactone) blend membranes: preparation and morphological characterisation , 2000 .

[35]  R. Miron,et al.  Membranes for guided tissue and bone regeneration , 2013 .

[36]  L. Yubao,et al.  Morphology and composition of nanograde calcium phosphate needle-like crystals formed by simple hydrothermal treatment , 1994 .

[37]  U. Meyer,et al.  Attachment Kinetics and Differentiations of Osteoblasts on Different Biomaterials , 1993 .

[39]  Robert Langer,et al.  Polymers of biological and biomedical significance , 1993 .

[40]  M. Malinconico,et al.  Development and characterization of porous membranes with “sandwich-like” structure based on biocompatible, immiscible polymer blends , 2007 .

[41]  Michel Vert,et al.  Degradation and cell culture studies on block copolymers prepared by ring opening polymerization of epsilon-caprolactone in the presence of poly(ethylene glycol). , 2004, Journal of biomedical materials research. Part A.

[42]  P. Fabbri,et al.  Porous scaffolds of polycaprolactone reinforced with in situ generated hydroxyapatite for bone tissue engineering , 2010, Journal of materials science. Materials in medicine.

[43]  M. Malinconico,et al.  Development of Innovative Biopolymers and Related Composites for Bone Tissue Regeneration: Study of Their Interaction with Human Osteoprogenitor Cells , 2012, Journal of applied biomaterials & functional materials.

[44]  C. Tonda-Turo,et al.  Polymeric membranes for guided bone regeneration , 2011, Biotechnology journal.

[45]  W. Wallace,et al.  Precipitation casting of polycaprolactone for applications in tissue engineering and drug delivery. , 2004, Biomaterials.