The optimal carrier for BMP-2: a comparison of collagen versus fibrin matrix

Schützenberger, Sebastian; Schultz, A.; Hausner, T.; Hopf, R.; Zanoni, Gerald; Morton, Tatjana; Kropik, K.; Griensven, Martijn van; Redl, Heinz

doi:10.1007/s00402-012-1551-2

Cited by 40 publications

(26 citation statements)

References 27 publications

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“…BMPs induced MSCs to migrate to bone-forming sites, differentiate into an osteoblast lineage, and regenerate bone. 157 Local pharmacokinetics are very important for the therapeutic efficacy of BMPs. For example, when …”

Section: Bmp Deliverymentioning

confidence: 99%

“…158 Besides this minimal effect, the rapid release of BMP-2 can cause adverse effects and will require more frequent administration which is costly. 157 Therefore, it is necessary to develop a delivery system that can release BMPs locally for a sufficient time period and concentration. Among several different BMP carriers, a fibrin matrix is considered as an excellent carrier.…”

mentioning

confidence: 99%

“…Among several different BMP carriers, a fibrin matrix is considered as an excellent carrier. Schützenberger et al 157 added BMP-2 to fibrinogen and then mixed it with thrombin. Their in vivo study in a rat femoral defect showed that although compared to a commercially available absorbable collagen sponge-BMP-2 system, a 7-fold lower dose of BMP-2 used in fibrin gels, the fibrin-BMP-2 system would result in equal or superior bone formation versus a collagen/ BMP-2 system.…”

mentioning

confidence: 99%

“…Their in vivo study in a rat femoral defect showed that although compared to a commercially available absorbable collagen sponge-BMP-2 system, a 7-fold lower dose of BMP-2 used in fibrin gels, the fibrin-BMP-2 system would result in equal or superior bone formation versus a collagen/ BMP-2 system. 157 As in the case of cell delivery, the addition of osteoconductive agents such as β-tricalcium phosphate to a fibrin carrier intensifies the efficacy of a delivery system. 159 Fibrin glue was also used to encapsulate collagen sponges loaded with BMPs and block bone formation in undesired areas by limiting BMP diffusion.…”

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confidence: 99%

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A review of fibrin and fibrin composites for bone tissue engineering

Noori

Ashrafi

Vaez-Ghaemi

et al. 2017

IJN

377

256

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Tissue engineering has emerged as a new treatment approach for bone repair and regeneration seeking to address limitations associated with current therapies, such as autologous bone grafting. While many bone tissue engineering approaches have traditionally focused on synthetic materials (such as polymers or hydrogels), there has been a lot of excitement surrounding the use of natural materials due to their biologically inspired properties. Fibrin is a natural scaffold formed following tissue injury that initiates hemostasis and provides the initial matrix useful for cell adhesion, migration, proliferation, and differentiation. Fibrin has captured the interest of bone tissue engineers due to its excellent biocompatibility, controllable biodegradability, and ability to deliver cells and biomolecules. Fibrin is particularly appealing because its precursors, fibrinogen, and thrombin, which can be derived from the patient’s own blood, enable the fabrication of completely autologous scaffolds. In this article, we highlight the unique properties of fibrin as a scaffolding material to treat bone defects. Moreover, we emphasize its role in bone tissue engineering nanocomposites where approaches further emulate the natural nanostructured features of bone when using fibrin and other nanomaterials. We also review the preparation methods of fibrin glue and then discuss a wide range of fibrin applications in bone tissue engineering. These include the delivery of cells and/or biomolecules to a defect site, distributing cells, and/or growth factors throughout other pre-formed scaffolds and enhancing the physical as well as biological properties of other biomaterials. Thoughts on the future direction of fibrin research for bone tissue engineering are also presented. In the future, the development of fibrin precursors as recombinant proteins will solve problems associated with using multiple or single-donor fibrin glue, and the combination of nanomaterials that allow for the incorporation of biomolecules with fibrin will significantly improve the efficacy of fibrin for numerous bone tissue engineering applications.

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Section: Bmp Deliverymentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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A review of fibrin and fibrin composites for bone tissue engineering

Noori

Ashrafi

Vaez-Ghaemi

et al. 2017

IJN

377

256

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“…In addition, it is absorbable and supports angiogenic ingrowth. 55,56 In this study, soaking the scaffolds with fibrin resulted in inferior results when compared with autologous serum and cell culture medium, possibly due to the special nanostructured architecture. Comparison of the two combination groups with expanded MSC and rhBMP-2 in fibrin and serum demonstrated that fibrin is not crucial for the delivery of the growth factor BMP-2 over time.…”

Section: New Bone Formation Depending On Implanted Cells and Carrier mentioning

confidence: 70%

Autologous serum improves bone formation in a primary stable silica-embedded nanohydroxyapatite bone substitute in combination with mesenchymal stem cells and rhBMP-2 in the sheep model

Boos

Weigand

Deschler

et al. 2014

IJN

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New therapeutic strategies are required for critical size bone defects, because the gold standard of transplanting autologous bone from an unharmed area of the body often leads to several severe side effects and disadvantages for the patient. For years, tissue engineering approaches have been seeking a stable, axially vascularized transplantable bone replacement suitable for transplantation into the recipient bed with pre-existing insufficient conditions. For this reason, the arteriovenous loop model was developed and various bone substitutes have been vascularized. However, it has not been possible thus far to engineer a primary stable and axially vascularized transplantable bone substitute. For that purpose, a primary stable silica-embedded nanohydroxyapatite (HA) bone substitute in combination with blood, bone marrow, expanded, or directly retransplanted mesenchymal stem cells, recombinant human bone morphogenetic protein 2 (rhBMP-2), and different carrier materials (fibrin, cell culture medium, autologous serum) was tested subcutaneously for 4 or 12 weeks in the sheep model. Autologous serum lead to an early matrix change during degradation of the bone substitute and formation of new bone tissue. The best results were achieved in the group combining mesenchymal stem cells expanded with 60 μg/mL rhBMP-2 in autologous serum. Better ingrowth of fibrovascular tissue could be detected in the autologous serum group compared with the control (fibrin). Osteoclastic activity indicating an active bone remodeling process was observed after 4 weeks, particularly in the group with autologous serum and after 12 weeks in every experimental group. This study clearly demonstrates the positive effects of autologous serum in combination with mesenchymal stem cells and rhBMP-2 on bone formation in a primary stable silica-embedded nano-HA bone grafting material in the sheep model. In further experiments, the results will be transferred to the sheep arteriovenous loop model in order to engineer an axially vascularized primary stable bone replacement in clinically relevant size for free transplantation.

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