SPINE Volume 35, Number 7, pp 740 –746 ©2010, Lippincott Williams & Wilkins Cages Augmented With Mineralized Collagen and Platelet-Rich Plasma as an Osteoconductive/Inductive Combination for Interbody Fusion Matti Scholz, MD,* Philipp Schleicher, MD,* Tanja Eindorf, MD,† Frank Friedersdorff, MD,† Michael Gelinsky, PhD,‡ Ulla Ko ¨nig, PhD,‡ Andreas Sewing, PhD,§ Norbert P. Haas, MD,† and Frank Kandziora, MD* Study Design. After anterior cervical discectomy, fu- sion was radiologically, biomechanically, and histologi- cally assessed in a sheep spine fusion model. Objective. To evaluate the efficacy of a platelet-rich plasma (PRP) application combined with a mineralized collagen matrix (MCM) as an alternative to autologous cancellous iliac crest bone grafts in a spine fusion model. Summary of Background Data. PRP has the ability to stimulate bone and tissue healing. MCM is a recently developed osteoconductive material. Up to now, no com- parative evaluation of PRP in combination with a MCM at the cervical spine has been performed in vivo. Methods. Twenty-four sheep (N = 8/group) underwent C3/4 discectomy and fusion: group 1, titanium cage filled with autologous cancellous iliac crest bone graft; group 2, titanium cage filled with MCM; and group 3, titanium cage filled with MCM and PRP. Radiographic evaluation was performed before surgery and after 1, 2, 4, 8, and 12 weeks, respectively. After 12 weeks, fusion sites were evaluated using functional radiographic views and quan- titative computed tomographic scans to assess bone min- eral density. Furthermore, histomorphologic and histo- morphometrical analyses were performed to evaluate fusion. Results. In comparison with the titanium cage group filled with autologous cancellous iliac crest bone grafts representing the control group, MCM-alone group showed a slightly lower fusion rate in the radiographic and the histomorphometrical analysis. The addition of PRP could not enhance this finding. There was no signif- icant difference between MCM and MCM + PRP group in radiologic and histologic findings. Conclusion. The MCM alone is not able to replace autologous bone grafts. Early activation of the platelets by calcium, which is released from mineralized collagen, could be the reason for the insufficient osteoinductive effect of PRP. In consequence, the combined application of mineralized collagen and PRP had no significant os- teoinductive effect in this model. Key words: cervical spine, sheep, animal model, inter- body fusion, mineralized collagen matrix, PRP, autolo- gous bone graft. Spine 2010;35:740 –746 Cages filled with autologous cancellous bone graft (BG) are widely used in spinal fusion procedures. 1 However, harvesting the autograft is time consuming and results in significant donor side morbidity. 2–4 Many different ideas have been evaluated to avoid the use of autograft in spi- nal fusion. Until today, only a small number of options have demonstrated valuable results. One promising option is the combination of collagen and calcium phosphate, which seems to imitate effec- tively the osteoconductive characteristics of autologous bone. The properties of such composite materials have been assessed in several studies, however, with variable success. 5–10 One problem so far was to achieve a suitable ratio of both components and a uniform distribution of the calcium phosphate phase in a collagen sponge. 11 All currently available mineralized collagen scaffolds con- tain bovine type I collagen. The 3-dimensional and chemical structure tries to mimic the architecture and chemical composition of the extracellular matrix of bone including collagen fibrils and the nanocrystalline hy- droxyapatite mineral phase, forming a highly organized nanocomposite. 9,10,12 Some of these porous constructs have already demonstrated the ability to enhance pene- tration of osseous cells and blood capillaries into the material, resulting in faster ingrowth of bone. 10,12 Cellular events that follow tissue damage are con- trolled among others by platelets and the released growth factors. Platelets release a large variety of growth factors and cytokines after they adhere, aggregate, and form a fibrin mesh. Growth factors such as platelet- derived growth factor, platelet factor 4, transforming growth factor-, insulin-like growth factor, and others, as well as fibrinogen, fibronectin, osteocalcin, and others were found in platelet-rich plasma (PRP). 13 Impacts of most of these factors on bone and tissue regeneration have already been shown by many investigations. 2,14,15 In 1982, Knighton et al 16 described the capacity of platelets and fibrin to stimulate and accelerate the bone From the *Center for Spinal Surgery and Neurotraumatology, Trau- maclinic Frankfurt/Main, Germany; †Center for Musculosceletal Sur- gery, Charite ´—Universita ¨ tsmedizin Berlin, Berlin, Germany; ‡Max Bergmann Center of Biomaterials, Institute of Materials Science, Tech- nische Universita ¨ t Dresden, Dresden, Germany; and §Biomet Deut- schland GmbH, Berlin, Germany. Acknowledgment date: February 26, 2009. First revision date: July 6, 2009. Acceptance date: July 13, 2009. The device(s)/drug(s) that is/are the subject of this manuscript is/are not FDA-approved for this indication and is/are commercially available in the United States. Corporate/industry funds were received in support of this work. Al- though one or more of the author(s) has/have received or will receive benefits for personal or professional use benefits will be directed solely to a research fund, foundation, educational institution, or other non- profit organization which the author(s) has/have been associated. Address correspondence and reprint requests to Matti Scholz, MD, Center for Spinal Surgery and Neurotraumatology, Traumaclinic Frankfurt/Main, Friedberger Landstraße 430, 60389 Frankfurt/Main, Germany; E-mail: matti.scholz@bgu_frankfurt.de 740