Implant therapy of the atrophic maxilla – new opportunities by intelligent combination of growth factors, bone regeneration materials and types of implant? Back

Dr. Eva Dulger, Dr. Fred Bergmann, Dr. Angela Bergmann, Pantelis Petrakakis, Dr. Ricarda Jansen


The reconstruction of edentulous, atrophic jaws according to functional and esthetic factors not only restores chewing function, but leads to positive sychosocial effects and thus also improves the patient’s quality of life.1A sufficient and long-term stable bone site is the basis of long term successful implant therapy. Next to healthy and functional hard tissue, a type of implant should be used which can also be placed with sufficient primary stability into bone of poor quality. In specific, this applies to the restoration of the lateral maxilla:not only does bone resorption occur after tooth loss; one can also expect caudal expansion of the maxillary sinus. By conditioning the bone regeneration material with growth factors in combination with an implant which makes best use of the existing bone situation, it appears possible to positively affect the already clinically established therapeutic concepts for maxillary sinus augmentation. Despite extensive tissue regeneration the simultaneous implant placement is achievable, in particular the regeneration in combination with the growth factors is accelerated.

The innovative technology for obtaining growth and angiogenic factors plus an additional biologic fibrin-membrane for tissue coverage by centrifugation when processing a patient’s blood seems to have a positive effect on bone regeneration and healing when combining FRIOS Algipore and XiVE implants (DENTSPLY Friadent) specifically. One reason for this effect may be the fact that the fibrin “sticks” on the surface very well. Patients could thus be offered a therapeutic concept where the number of procedures is reduced, no additional donor site is required by using bone regeneration material, costs are reduced, and where no animal or synthetic products are used for bone reconstruction. The following discourse briefly highlights the effects of growth factors on wound healing and how osseointegration is integrated into the biological processes.

Osteoinduction and osteoconduction

Osteogenic (bone-forming) processes in physiological bone tissue are differentiated into osteoconductive and osteoinductive processes. Osteoconduction takes place in bone tissue as a result of chemical and/or physical factors. This results in oriented growth of osteoblasts on autogenous structures or implant materials.2 Osteoinduction is described as the active process of chemotactic attraction and differentiation of mesenchymal bone progenitor cells. Growth factors, as contained in platelet-rich plasma (PRP), have an initiating and differentiating effect on bone cells.3

Platelet-rich plasma (PRP)

Platelet-rich plasma (PRP) has been used in reconstructive therapy for about 20 years. As platelets fulfill a central regulatory role during the inflammatory phase of the hard tissue, the local administration of platelet concentrates to the wound area and can accelerate or improve wound healing.4,5 The average normal serum level of platelets is approximately 200,000 cells per μl blood. The fivefold volume of 1,000,000 cells per μl blood is described as the optimal concentration of PRP for effective wound healing. Concentrations below or above this value are said not to have any effect on wound healing.5

PRP is obtained from the venous blood of patients to exclude the risk of transmitting infections, of allergies or incompatibilities.6

Improved wound healing is attributed to the effects of different growth factors
contained in the platelet fraction, such as BMP (Bone Morphogenetic Protein), PDGF (Platelet-derived Growth Factor), TGF-β-1 (Transforming Growth Factor β-1), IGF-1 (Insulin-like Growth Factor Type 1), VEGF (Vascular Endothelial Growth Factor), bFGF (Basic Fibroplast Growth Factor) and EGF (Epidermal Growth Factor).7–9 These growth factors are decisive for the initiation and maintenance of the tissue repair and healing mechanisms. They have both an accelerating effect on the regeneration of damaged tissue, as well as on controlled cell migration (chemotaxis), cell proliferation and cell differentiation, as well as angiogenesis. Furthermore, the proteins affect intercellular communication and transmit information for interaction with cell membrane receptors.

With the classic method using centrifugation, whole blood is fractionated into three components. Platelet-rich plasma is obtained from the middle fraction. The upper layer consists of platelet-poor, cell-free plasma (Platelet-poor Plasma PPP) whereas the bottom layer consists of erythrocytes primarily.

PRGF and fibrin

The PRGF system (Plasma Rich in Growth Factors) according to Anitua also utilizes the positive effect of growth factors and proteins on the wound healing of hard and soft tissue. There is no need for bovine thrombine, only accelerated by CaCl2.

In this process the autogenous blood is also centrifuged, however, in contrast to the conventional centrifugation method, four fractions are obtained instead of three (BTI centrifuge, Biotechnology Institute, Miňao, Spain). Besides the three known plasma fractions, this process produces autogenous fibrin as a fourth phase.10 Acting as a membrane, this fibrin after cross-linking with its excellent elastic and blood-clotting properties, serves as wound coverage and supports haemostasis during the first few hours after surgical intervention, and later on as lining for the soft tissue. Fibrin protects the wound underneath the mucosal flap and reduces the risk of sutural dehiscence. By employing the PRGF technique it thus seems possible to also promote wound healing long-term by applying growth factors and fibrin to the surgical site.

The combination of PRGF with autogenous bone transplants can have a positive effect on the trabecular bone structure and on bone regeneration, and apparently accelerate the formation of mature bone substance.11 The joint use of the PRGF technique together with xenogenic bone grafting materials demonstrates advantages in handling and the application of the mixture, as well as apparently leading to an improvement and acceleration of osteoconductive effects during the healing period.12

Stability of the implant site

If bone is lost for reasons of trauma, infection or resorption processes following tooth loss, the provision of a sufficiently dimensioned implant site can usually only be achieved by surgical intervention in conjunction with augmentative procedures.13

Autogenous, allogeneic or xenogenic materials can be used for the surgical  regeneration of bone defects. Autogenous bone is still considered as the gold standard for replenishing defects and bone regeneration; however, it is subject to limitations due to the relatively low availability of donor bone. The additional surgical stress for the patient when a second surcigal site for harvesting sufficient amount of bone becomes necessary and possibly related postoperative complications are disadvantageous as well. Bone grafting can lead to a so-called “donor-site morbidity” which presents as postoperative hematomas, secondary bleeding, infections and impaired wound healing. These limitations led to the search for alternatives to autogenous bone.

Today, a number of xenogenic products are available. These may be of bovine origin, the bones of cattle often being the source product. According to the manufacturers of bovine products the risk of prion transfer is excluded by proper professional removal of organic material during processing. Despite the good clinical results with these materials it is also evident that resorption or remodeling processes could not be observed in the grafts, even after longer periods in-situ.14Thus, the grafted particles are only surrounded by new bone, like foreign matter, but not replaced by autogenous bone.

Also of xenogenic origin, but derived from plants, is the bone regeneration material FRIOS Algipore, which is obtained from the calcium carbonate structure of the red algae Corallina officinalis and Amphiroa ephedra. This so-called phycogenic hydroxylapatite consists of a honeycomb-like structure with high microporosity and a pronounced network of pores. The basic structure of Algipore is reminiscent of the Havers and Volkmann channels in natural bone.15 This spatially interlinked structure facilitates the formation of vessels from the surrounding bone and promotes osteoconduction. Algipore differs from grafts of bovine origin by its specific surface structure coupled with its osteoconductive properties. Compared with Algipore, these hardly provide porosity, or only at a superficial level. It is this porosity which appears causal for the good osteoconductive properties of Algipore and its sufficient resorption by local bone.14

Clinical long-term results for sinus floor elevations have demonstrated that the joint use of platelet-rich plasma with phycogenic hydroxyapatites in combination with implant placement into the lateral maxilla, already resulted in very good bone regeneration of the implant site after six months and led to high survival rates of the implants which are comparable and in some cases superior to the results achieved with pure autogenous derived bone grafts.16

Osseointegration of implants

Osseointegration is comparable to the healing processes in bone. Regeneration of the bone and in the contact area between bone and implant takes place in three phases.17–19 The first phase is comparable to an acute inflammation of tissue. During this phase, migration of granulocytes and macrophages takes place, as does platelet activation. Phase 2 includes the proliferation and differentiation of mesenchymal bone progenitor cells into osteoblasts. Phase 3 is characterized by remodelling and regeneration processes in the tissue concerned.19

Implant placement at the implant site initially leads to a destruction of bone continuity followed by hematoma formation and an inflammatory reaction in the tissue. Growth factors and cytokines from the tissue then lead to migration and differentiation of bone cells in the affected area. In the subsequent healing process between implant and bone one distinguishes between primary and secondary healing or contact and distance osteogenesis. Distance osteogenesis is regarded as an unfavorable type of implant integration. In this type of healing there is no direct connection between the implant surface and the surrounding bone. The contact area between bone and implant consists of connective tissue.17Bone healing originates from the “old” bone site and new bone formation does not take place at the implant.3

However, in the case of contact osteogenesis one observes de-novo bone formation in the region of the implant surface. This type of new bone formation results from migration of osteoprogenitor cells to the implant surface area where they differentiate to osteoblasts.20

The role of the surface structure of implants on the healing process

The type of osseointegration of implants is determined significantly by the chemical composition, the charge, the roughness, and the morphology of the implant  surface.3,17,21 Grit-blasted and thermally acid-etched titanium surfaces, such as the FRIADENT plus surface of the XiVE implant, offer proteins and bone precursor cells significantly increased attachment potential in terms of microstructure as well as possessing osteoconductive properties.17,22,23 The bonding of proteins and cells is accelerated by the initial hydrophobic properties of the FRIADENT plus implant surface.24

As the good implant interface properties support the initial healing processes, the XiVE implant can also be used safely and predictably in areas with low bone density.25,26

Primary stability even with poor bone support

Due to the combination of thread design and bone-specific preparation protocol, XiVE also achieves sufficient primary stability in bone with poor quality even in case of simultaneous grafting.27 When preparing the implant site in cancellous bone, primary stability is increased by maximum utilization of the condensing thread design. Longterm results demonstrate a high success rate with XiVE implants which can also be attributed to the macro and micro design of the implant system.28 The initial results of a current study by Gerlach et al. on the primary stability of XiVE implants in freshly grafted maxillary sinuses appear to confirm this yet again.

Clinical case

Another clinical study is also being conducted to provide clinical data on the properties of the osteoconductive bone regeneration material Algipore in conjunction with healingpromoting PRGF, the autogenous fibrin membrane, and the XiVE implant. In the following illustrated example, the procedure used in the investigations is explained showing simultaneous implant placement and sinus grafting procedure (Figures 1–10).


The positive clinical results in this patient case with singlestage sinus floor elevation and implant placement indicate a bone healing effect of FRIOS Algipore, conditioned with PRGF and supplemented with a fibrin membrane. In combination with the XiVE implant system which has been proven clinically for over ten years, this surgical procedure represents a secure and predictable treatment method in areas with low bone density.

Further investigations are necessary to explore the exact mode of action and possible interactive tendencies of the implants, bone forming materials and specially prepared PRGF used in this clinical example. Answers to these questions are of scientific interest and will be published in the future in connection with ongoing studies.


1. McGrath C, Bedi R. Severe tooth loss among UK adults – who goes for oral rehabilitation? J Oral Rehabil 2002; 29: 240–4.

2. Wintermantel E, et al. Medizintechnik Life Science Engineering. Springer Verlag
Berlin-Heidelberg 2008.

3. Schmidmaier G, Wildemann B. Biologische und physiologische Grundlagen. In Gradinger R, Gollwitzer H. (ed.): Ossäre Integration. Springer Medizin Verlag, Heidelberg 2006, 25–9.

4. Marx R. Platelet-rich plasma: evidence to support its use. J Oral Maxillofac Surg 2004; 62: 489–96.

5. Marx RE. What is PRP and what is not PRP? Implant Dent 2001; 10: 225–8.

6. Nikolidakis D, Jansen JA. The biology of platelet-rich plasma and its application in oral surgery: literature review. Tissue Eng Part B Rev 2008; 14: 249–58.

7. Lind M. Growth factor stimulation of bone healing. Effects on osteoblasts, osteomies, and implants fixation. Acta Orthop Scand Suppl 1998; 283:2–37.

8. Nakagawa M, et al. Vascular endothelial growth factor (VEGF) directly enhances osteoclastic bone resorption and survival of mature osteoclasts. FEBS Lett 2000; 473(2): 161–4.

9. Meraw SJ, et al. Treatment of peri-implant defects with combination growth factor cement. J Periodontol 2000; 71(1): 8–13.

10. Weibrich G, et al. Das PRGFSystem nach Anitua zur Anreicherung von Thrombozyten und Wachstumsfaktoren im Plasma–Methodenvorstellung und Pilotstudie-. Z Zahnärztl Implantol 2002; 18(2): 84–9.

11. Anitua E. Plasma rich in growth factors: preliminary results of use in the preparation of future sites for implants. Int J Oral Maxillofac Impl 1999; 14:529–35.

12. Anitua E. The use of plasma rich growth factors in oral surgery. Pract Proced Aesthet Dent 2001; 13: 487–93.

13. Chiapasco M, et al. Bone augmentation procedures in implant dentistry. Int J Oral Maxillofac Implants 2009; 24 Suppl: 237–59.

14. Ewers R, et al. Histologic findings at augmented bone areas supplied with two different bone substitute materials combined with sinus floor lifting. Report of
one case. Clin Oral Implants Res 2004; 15: 96–100.

15. Reichart P, et al. Curriculum Zahnärztliche Chirurgie. Quintessenz Verlag, Berlin, Chicago, London, Tokio 2002.

16. Ewers R. Maxilla sinus grafting with marine algae derived bone forming material: a clinical report of long-term results. J Oral Maxillofac Surg 2005; 63:

17. Gehrke P. Mechanismen der knöchernen Integration: Biotechnologie für eine
beschleunigte Osteogenese. Implantologie Journal 2004; 8:14–9.

18. Intini G. The use of platelet-rich plasma in bone reconstruction therapy. Biomaterials 2009; 30: 4956–66.

19. Davies JE. Understanding peri-implant endosseous healing. J Dent Educ 2003; 67(8): 932–49.

20. Davies JE. Mechanisms of endosseous integration. Int J Prosthodont 1998; 11(5):391–401.

21. Shalabi M, et al. Implant surface roughness and bone healing: a systematic review. J Dent Res 2006; 85: 496–500.

22. Hsu S, et al. Characterization and biocompatibility of a titanium dental implant with a laser irradiated and dual-acid etched surface. Biomed Mater Eng 2007;17: 53–68.

23. Monsees T, et al. Einfluss von Nanostrukturierung und Oberflächenladung auf die Bioaktivität. In Peters K, König D. (ed.): Fortbildung Osteologie 2. Steinkopff Verlag, 2008, 105–10.

24. Rupp F, et al. Roughness induced dynamic changes of wettability of acid etched titanium implant modifications. J Biomaterials 2004; 25: 1429–38.

25. Park J, et al. Osteoconductivity of hydrophilic microstructured titanium implants with phosphate ion chemistry. Acta Biomater 2009; 5: 2311–21.

26. Park JW, et al. Enhanced osteoconductivity of microstructured titanium implants (XiVE S CELLplus) by addition of surface calcium chemistry: a histomorphometric study in the rabbit femur. Clin Oral Implants Res 2009; 20(7): 684–90.

27. Degidi M, et al. Primary stability determination by means of insertion torque and RFA in a sample of 4135 implants. Clin Implant Dent Relat Res (2010).

28. Gehrke P, et al. Zirconium implant abutments: fracture strength and influence of cyclic loading on retaining-screw loosening. Quintessence Int 2006; 37: 19–26.