Poly-ε-caprolactone Coated and Functionalized Porous Titanium and Magnesium Implants for Enhancing Angiogenesis in Critically Sized Bone Defects

For healing of critically sized bone defects, biocompatible and angiogenesis supporting implants are favorable. Murine osteoblasts showed equal proliferation behavior on the polymers poly-ε-caprolactone (PCL) and poly-(3-hydroxybutyrate)/poly-(4-hydroxybutyrate) (P(3HB)/P(4HB)). As vitality was significantly better for PCL, it was chosen as a suitable coating material for further experiments. Titanium implants with 600 µm pore size were evaluated and found to be a good implant material for bone, as primary osteoblasts showed a vitality and proliferation onto the implants comparable to well bottom (WB). Pure porous titanium implants and PCL coated porous titanium implants were compared using Live Cell Imaging (LCI) with Green fluorescent protein (GFP)-osteoblasts. Cell count and cell covered area did not differ between the implants after seven days. To improve ingrowth of blood vessels into porous implants, proangiogenic factors like Vascular Endothelial Growth Factor (VEGF) and High Mobility Group Box 1 (HMGB1) were incorporated into PCL coated, porous titanium and magnesium implants. An angiogenesis assay was performed to establish an in vitro method for evaluating the impact of metallic implants on angiogenesis to reduce and refine animal experiments in future. Incorporated concentrations of proangiogenic factors were probably too low, as they did not lead to any effect. Magnesium implants did not yield evaluable results, as they led to pH increase and subsequent cell death.

[1]  R. Carano,et al.  Angiogenesis and bone repair. , 2003, Drug discovery today.

[2]  A. Rinkevich,et al.  Elastic properties of a porous titanium-bone tissue composite. , 2015, Materials science & engineering. C, Materials for biological applications.

[3]  David P Martin,et al.  Poly-4-hydroxybutyrate (P4HB): a new generation of resorbable medical devices for tissue repair and regeneration , 2013, Biomedizinische Technik. Biomedical engineering.

[4]  Ralf Schumacher,et al.  Selective laser melted titanium implants: a new technique for the reconstruction of extensive zygomatic complex defects , 2015, Maxillofacial Plastic and Reconstructive Surgery.

[5]  Cleo Choong,et al.  Three-dimensional scaffolds for tissue engineering applications: role of porosity and pore size. , 2013, Tissue engineering. Part B, Reviews.

[6]  M. Horton,et al.  Cell adhesion molecules in human osteoblasts: structure and function. , 2001, Histology and histopathology.

[7]  Colleen L Flanagan,et al.  Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering. , 2005, Biomaterials.

[8]  Berend Denkena,et al.  Biodegradable magnesium implants for orthopedic applications , 2012, Journal of Materials Science.

[9]  M. Nishibori,et al.  High mobility group box 1 complexed with heparin induced angiogenesis in a matrigel plug assay. , 2009, Acta medica Okayama.

[10]  J. Kruth,et al.  A study of the microstructural evolution during selective laser melting of Ti–6Al–4V , 2010 .

[11]  Changsheng Liu,et al.  Segmental bone regeneration using rhBMP-2-loaded collagen/chitosan microspheres composite scaffold in a rabbit model , 2012, Biomedical materials.

[12]  W. Friess,et al.  Collagen sponges for bone regeneration with rhBMP-2. , 2003, Advanced drug delivery reviews.

[13]  N. Gellrich,et al.  Comparison of Selective Laser Melted Titanium and Magnesium Implants Coated with PCL , 2015, International journal of molecular sciences.

[14]  T. Albert,et al.  Donor Site Morbidity After Anterior Iliac Crest Bone Harvest for Single-Level Anterior Cervical Discectomy and Fusion , 2003, Spine.

[15]  Baki Hazer,et al.  Amphiphilic Poly ( 3-hydroxy alkanoate ) s : Potential Candidates for Medical Applications , 2010 .

[16]  Napoleone Ferrara,et al.  Vascular endothelial growth factor: basic science and clinical progress. , 2004, Endocrine reviews.

[17]  J. P. Li,et al.  Cancellous bone from porous T{i}6Al4V by multiple coating technique , 2006, Journal of materials science. Materials in medicine.

[18]  N. Gellrich,et al.  Characterisation of Cell Growth on Titanium Scaffolds Made by Selective Laser Melting for Tissue Engineering , 2013, Biomedizinische Technik. Biomedical engineering.

[19]  Ke Zhu,et al.  Measurement of the dynamic Young’s modulus of porous titanium and Ti6Al4V , 2007 .

[20]  N. Gellrich,et al.  SLM Produced Porous Titanium Implant Improvements for Enhanced Vascularization and Osteoblast Seeding , 2015, International journal of molecular sciences.

[21]  Andreas Gebhardt,et al.  Understanding Additive Manufacturing , 2011 .

[22]  A. A. Zadpoor,et al.  Selective laser melting‐produced porous titanium scaffolds regenerate bone in critical size cortical bone defects , 2013, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[23]  V. Alt,et al.  Histological Comparison of New Biodegradable Magnesium-Based Implants for Maxillofacial Applications , 2015, Journal of Maxillofacial and Oral Surgery.

[24]  J. Nellesen,et al.  Magnesium hydroxide temporarily enhancing osteoblast activity and decreasing the osteoclast number in peri-implant bone remodelling. , 2010, Acta biomaterialia.

[25]  J. Kanczler,et al.  Osteogenesis and angiogenesis: the potential for engineering bone. , 2008, European cells & materials.

[26]  D J Mooney,et al.  Bone Regeneration via a Mineral Substrate and Induced Angiogenesis , 2004, Journal of dental research.

[27]  M. Menger,et al.  The dorsal skinfold chamber: window into the dynamic interaction of biomaterials with their surrounding host tissue. , 2011, European cells & materials.

[28]  Katrin Sternberg,et al.  Surface functionalization of poly(ε-caprolactone) improves its biocompatibility as scaffold material for bioartificial vessel prostheses. , 2011, Journal of biomedical materials research. Part B, Applied biomaterials.

[29]  L. Neff,et al.  Thy‐1 Antigen Expression by Cells in the Osteoblast Lineage , 1999, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[30]  Qiong Wu,et al.  Medical Application of Microbial Biopolyesters Polyhydroxyalkanoates , 2009, Artificial cells, blood substitutes, and immobilization biotechnology.

[31]  D. Hutmacher,et al.  The return of a forgotten polymer : Polycaprolactone in the 21st century , 2009 .

[32]  K. Shadan,et al.  Available online: , 2012 .

[33]  T. Woodfield,et al.  Monetite and brushite coated magnesium: in vivo and in vitro models for degradation analysis , 2013, Journal of Materials Science: Materials in Medicine.

[34]  Alexander Schramm,et al.  Alveolar zygomatic buttress: A new donor site for limited preimplant augmentation procedures. , 2007, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[35]  Mitsuo Niinomi,et al.  Mechanical biocompatibilities of titanium alloys for biomedical applications. , 2008, Journal of the mechanical behavior of biomedical materials.

[36]  Volker Wesling,et al.  Selective Laser Melting of Magnesium and Magnesium Alloys , 2013 .

[37]  J. Goulet,et al.  Autogenous Iliac Crest Bone Graft: Complications and Functional Assessment , 1997, Clinical orthopaedics and related research.

[38]  M. Pensak,et al.  Biofunctionalizing devitalized bone allografts through polymer-mediated short and long term growth factor delivery. , 2015, Journal of biomedical materials research. Part A.