Andreas Sewing

Biomimetic coatings functionalized with adhesion peptides for dental implants.

A complete biological integration into the surrounding tissues (bone, gingiva) is a critical step for clinical success of a dental implant. In this work biomimetic coatings consisting either of collagen type I (for the gingiva region) and hydroxyapatite (HAP) or mineralized collagen (for the bone interface) have been developed as suitable surfaces regarding the interfaces. Additionally, using these biomimetic coatings as a matrix, adhesion peptides were bound to further increase the specificity of titanium implant surfaces. To enhance cell attachment in the gingiva region, a linear adhesion peptide developed from a laminin sequence (TWYKIAFQRNRK) was bound to collagen, whereas for the bone interface, a cyclic RGD peptide was bound to HAP and mineralized collagen using adequate anchor systems. The biological potential of these coatings deduced from cell attachment experiments with HaCaT human keratinocytes and MC3T3-E1 mouse osteoblasts showed the best results for collagen and laminin sequence coating for the gingiva region and mineralized collagen and RGD peptide coatings for regions with bone contact. Our concept opens promising approaches to improve the biological integration of dental implants.© 2001 Kluwer Academic Publishers

Tools for tissue engineering of mineralized oral structures

Abstract This paper presents a short review of three groups of tools which can be or are used for the tissue engineering of mineralized oral structures: growth factor delivery systems (GFDS) and surface bioactivation with covalent bound peptides or with nanomechanically linked proteins. According to the reported personal experience of the authors, GFDS have to face the following challenging issue before being used routinely in dentistry, e.g., as a tool for reparative dentinogenesis or bone healing: adaptation of the GFDS design to the tissue where it will be implanted in order to deliver the right dose of growth factor (GF) at the right time. The bioactivation of surfaces, for example of dental implants, with covalent bound peptides or nanomechanically linked proteins represents a second innovative way to improve dental health in the future. Here we report on the experimental use of cyclic RGD peptides grafted on polymethylmethacrylate to improve osteoblast adhesion. Furthermore, we show the potential advantage of immobilizing and incorporating collagen I on titanium implant surfaces. These techniques or a combination of them will help to create improvements, for example, of dental implants in the near future. They will also help to promote bone and dentin regeneration.

Cages augmented with mineralized collagen and platelet-rich plasma as an osteoconductive/inductive combination for interbody fusion.

Study Design. After anterior cervical discectomy, fusion was radiologically, biomechanically, and histologically 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 comparative 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 quantitative computed tomographic scans to assess bone mineral density. Furthermore, histomorphologic and histomorphometrical 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 significant 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 osteoinductive effect in this model.

Cyclic-rgd Is as Effective as rhbmp-2 in Anterior Interbody Fusion of the Sheep Cervical Spine

Study Design. Radiological and histological assessment of fusion status after anterior cervical discectomy and fusion (ACDF) procedure in a sheep spinal fusion model. Objective. To evaluate the efficacy of cyclic arginine-glycine-aspartic (cRGD) in comparison with recombinant human bone morphogenetic protein-2 (rhBMP-2) on a mineralized collagen matrix (MCM). Summary of Background Data. A previous evaluation of MCM alone in comparison with autologous bone graft alone was not able to show an advantage on spinal fusion. The cRGD peptide sequence plays a major role in mediating cell adhesion. Studies have demonstrated enhances osteoblasts adhesion resulting in increased periimplant bone formation after implantcoating with cRGD. rhBMP-2 has already proven its ability to enhance spinal fusion. To date, no comparative in vivo evaluation of cRGD and rhBMP-2 in combination with a MCM for spinal fusion has been performed. Methods. Twenty-four sheep (N = 8/group) underwent C3–C4 fusion. Implants: group 1: titanium cage with MCM and rhBMP-2; group 2: titanium cage with MCM and cRGD; control group: titanium cage with MCM alone. After 12 weeks fusion sites were evaluated by computed tomography to assess fusion status, bone mineral density as well as bony callus volume. Furthermore, histomorphological and histomorphometrical analysis of the fusion sites were performed. Results. In comparison with the control group, cRGD, and rhBMP-2 groups showed a higher fusion rate in radiographical findings and a higher degree of interbody fusion in histomorphometrical analysis (P < 0.05). There was no significant difference in radiographical and histological parameters between the rhBMP-2 and the cRGD group. Although rhBMP-2 demonstrated ectopic prevertebral bone formations, this effect was less prominent in the cRGD group. Conclusion. In this animal model the combination of cRGD and a mineralized collagen matrix showed superior fusion results in comparison with the mineralized collagen alone. Further, cRGD was comparably effective to rhBMP-2 in promoting interbody fusion by demonstrating less ectopic bone formations.