Osseointegration of acellular and cellularized osteoconductive scaffolds: Is tissue engineering using mesenchymal stem cells necessary for implant fixation? Elena Garc  ıa-Gareta, Jia Hua, Gordon W. Blunn John Scales Centre for Biomedical Engineering, Institute of Orthopaedics and Musculoskeletal Science, University College London, Royal National Orthopaedic Hospital, Stanmore HA7 4LP, United Kingdom Received 5 March 2014; revised 14 May 2014; accepted 4 June 2014 Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.a.35256 Abstract: The main issue associated with revision total hip replacements (rTHRs) is how to generate new bone adjacent to implants and achieve fixation of the revision implant. In its simplest form, bone tissue engineering (BTE) combines cells and scaffolds in vitro to replace damaged or lost bone in vivo. Our aim was to develop BTE porous TiAl6V4 constructs with a calcium–phosphate coating without or with mesenchy- mal stem cells (MSCs) seeded throughout the entire porous structure to enhance new bone formation and which could be used for rTHRs. Porous titanium scaffolds made by selec- tive laser sintering were seeded throughout with autologous bone marrow MSCs and cultured in a perfusion bioreactor. Constructs were implanted in the medial femoral condyle of 20 skeletally mature mule sheep with and without a gap of 2.5 mm between the construct and the host bone. After 6 weeks, the addition of MSCs to the scaffolds did not signifi- cantly increase osseointegration or implant–bone fixation strength. However, in the defects with a gap, the cellularized constructs showed higher implant–bone contact area and implant–bone fixation strength. BTE can be applied to develop acellular or cellularized constructs with clinical application in rTHRs where a lack of bone stock is problem- atic. V C 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 00A:000–000, 2014. Key Words: bone tissue engineering, mesenchymal stem cells, in vivo, osseointegration, implant, bone fixation strength How to cite this article: Garc  ıa-Gareta E, Hua J, Blunn GW. 2014. Osseointegration of acellular and cellularized osteoconductive scaffolds: Is tissue engineering using mesenchymal stem cells necessary for implant fixation?. J Biomed Mater Res Part A 2014:00A:000–000. INTRODUCTION Aseptic loosening of total hip replacements (THRs) due to osteolysis results in a reduction in the bone stock, the loss of which compromises implant fixation in revision THR (rTHR). 1–5 Several techniques are used to reconstitute the bone stock at revision operations, such as impaction graft- ing using allograft or autograft. 6–11 However, these techni- ques present disadvantages: the supply of bone and donor site morbidity limit the use of autograft, 7,12 while the disad- vantages associated with the use of allograft are disease transmission and differences in graft preparation techniques which lead to inconsistency and unfavorable immune response. 7,8 Tissue engineering is based on understanding how tis- sue formation and regeneration work and its aim is to induce new functional tissues. 13,14 The present study pro- poses a novel tissue engineering approach to address the problem associated with poor bone stock and fixation of implants at rTHRs. Even in well-fixed revision implants gaps at the bone–implant interface occur and for long-term secure fixation gap filling and osseointegration of the implant is important. Porous metals offer mechanical properties, bone ingrowth and vascularization potential. 15–19 Therefore, a porous TiAl6V4 material, coated with a calcium–phos- phate (CaP) layer for added osteoconductivity, 15 was cho- sen for the study. Mesenchymal stem cells (MSCs) from bone marrow, which can differentiate into bone cells 20 and are already being used in clinical orthopedic applica- tions, 21 were the chosen cell source. They were uniformly cultured throughout the scaffold using a perfusion bio- reactor 22 and implanted in the femoral condyles of sheep to study new bone formation and implant–bone interface fixation. The hypothesis for this study was that the addition of MSCs to a porous metal scaffold coated with a CaP layer and implanted in an ovine femoral condyle model with and without a 2.5-mm gap will enhance rapid formation of bone within the implant, thus repairing adjacent defect areas and increasing fixation strength at rTHRs. Correspondence to: Dr. E. Garc  ıa-Gareta, RAFT Institute of Plastic Surgery, Mount Vernon Hospital, Northwood HA6 2RN, United Kingdom; e-mail: garciae@raft.ac.uk V C 2014 WILEY PERIODICALS, INC. 1