Development of porous polyurethane/strontium-substituted hydroxyapatite composites for bone regeneration Kemal Sariibrahimoglu, 1* Wanxun Yang, 1* Sander C. G. Leeuwenburgh, 1 Fang Yang, 1 Joop G. C. Wolke, 1 Yi Zuo, 2 Yubao Li, 2 John A. Jansen 1 1 Department of Biomaterials, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands 2 Research Center for Nano-Biomaterials, Analytical and Testing Center, Sichuan University, Chengdu 610064 China Received 9 June 2014; revised 12 August 2014; accepted 14 August 2014 Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.a.35327 Abstract: Polyurethane (PU) has been widely used for the biomedical applications but its potential for bone regenera- tion is limited due to its lack of osteoconductive properties. Strontium substituted hydroxyapatite (SrHA) particles, on the other hand, are known to exhibit a positive effect on bone formation. Therefore, the aim of this study was to (i) develop porous polyurethane scaffolds containing strontium SrHA nanoparticles (PU/SrHA) and (ii) compare their in vitro biolog- ical performance for applications in bone regeneration to PU scaffolds. SrHA and HA was synthesized using a conventional wet-chemical neutralization reaction at temperatures of 25, 50, and 80  C. Chemical analysis was performed by induc- tively coupled plasma-optical emission spectrometry. Synthe- sizing temperatures at 25 and at 50  C were selected for the composite preparation (abbreviated as HA-25, SrHA-25, HA- 50, and SrHA-50, respectively). PU was synthesized from iso- phorone diisocyanate, polytetramethylene ether glycol, and 1,4-butanediol. Composite scaffolds were prepared by addi- tion of HA or SrHA nanoparticles into PU scaffolds during polymer preparation. The results showed that the Sr content in HA nanoparticles increased with increasing synthesis tem- perature. The addition of nanoparticles decreased the elongation-at-break and tensile strength, but significantly increased the surface wettability of the PU scaffolds. In vitro degradation tests demonstrated that release of cations was significantly higher from PU/SrHA-50 composite scaffolds. Cell culture tests indicated that PU composites containing either HA or SrHA nanoparticles increased proliferation of bone marrow stem cells as compared to plain PU scaffolds, whereas osteogenic differentiation was not affected by the incorporation of HA nanoparticles irrespective of the incorpo- ration of Sr. V C 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 00A:000–000, 2014. Key Words: polyurethane, strontium-substituted hydroxyapa- tite, composite How to cite this article: Sariibrahimoglu K, Yang W, Leeuwenburgh SCG, Yang F, Wolke JGC, Zuo Y, Li Y, Jansen JA. 2014. Development of porous polyurethane/strontium-substituted hydroxyapatite composites for bone regeneration. J Biomed Mater Res Part A 2014:00A:000–000. INTRODUCTION Skeletal reconstruction with tissue-engineered implants is expected to obviate the need for autologous bone grafts. Because the major inorganic component of natural bone is carbonated hydroxyapatite, synthetic hydroxyapatite (HA) based materials have been extensively investigated for bone regeneration. Different from pure HA, bone and teeth mineral compositions contain various cationic and anionic substitu- tions such as carbonate (CO 3 ), magnesium (Mg), and stron- tium (Sr). Among these ions, Sr has attracted a particular interest 1–5 since Sr is an essential element required for hard tissue development. 6 Incorporating Sr ions into HA is of potential interest in the prevention of bone loss by stimulat- ing osteoblasts to secrete new bone matrix while reducing bone resorption. 7–9 Moreover, the occupation of a calcium (Ca) lattice site in HA by larger Sr ions also affects lattice dimensions, 10 crystallinity 7 and solubility, 11,12 thereby in- fluencing the chemical reactivity of Sr-containing HA. Sr-substituted apatite powders have been prepared by ion exchange of Sr for Ca upon high temperature sintering or by wet-chemical introduction into HA. Boanini et al. 11 showed that the local release of Sr from bone cement has antiresorp- tive effects while promoting osteoblast proliferation and gene expression when Sr ions are incorporated into HA at 90  C. Recently, Landi et al. 7 synthesized Sr-substituted HA powder at 37  C, yielding Ca release from HA which increased with increasing Sr substitution. Despite the close resemblance of HA-based ceramics to natural bone, their brittleness limits the widespread use of HA ceramics for load-bearing application. Therefore, HA par- ticles have been mixed with ductile and flexible polymers to form a composite that combines beneficial properties of both material classes. Polymers are advantageous since their phys- icochemical properties can be varied to desire by modifying their macromolecular structure. In that respect, polyur- ethanes (PU) are particularly interesting candidate polymers *These authors contributed equally to this work. Correspondence to: J. A. Jansen; e-mail: John.Jansen@radboudumc.nl V C 2014 WILEY PERIODICALS, INC. 1