Full regeneration of segmental bone defects using porous titanium implants loaded with BMP-2 containing fibrin gels

Abstract

Regeneration of load-bearing segmental bone defects is a major challenge in trauma and orthopaedic surgery. The ideal bone graft substitute is a biomaterial that provides immediate mechanical stability, while stimulating bone regeneration to completely bridge defects over a short period. Therefore, selective laser melted porous titanium, designed and fine-tuned to tolerate full load-bearing, was filled with a physiologically concentrated fibrin gel loaded with bone morphogenetic protein-2 (BMP-2). This biomaterial was used to graft critical-sized segmental femoral bone defects in rats. As a control, porous titanium implants were either left empty or filled with a fibrin gels without BMP-2. We evaluated bone regeneration, bone quality and mechanical strength of grafted femora using in vivo and ex vivo µCT scanning, histology, and torsion testing. This biomaterial completely regenerated and bridged the critical-sized bone defects within eight weeks. After twelve weeks, femora were anatomically re-shaped and revealed open medullary cavities. More importantly, new bone was formed throughout the entire porous titanium implants and grafted femora regained more than their innate mechanical stability: torsional strength exceeded twice their original strength. In conclusion, combining porous titanium implants with a physiologically concentrated fibrin gels loaded with BMP-2 improved bone regeneration in load-bearing segmental defects. This material combination now awaits its evaluation in larger animal models to show its suitability for grafting loadbearing defects in trauma and orthopaedic surgery.

A review of fibrin and fibrin composites for bone tissue engineering

“…18,19 Variations in experimental design, implantation site, and animal models as well as fibrinogen and thrombin concentrations are other parameters that make direct comparison of the research findings difficult. Moreover, to achieve the desired biological and/or physical properties for bone tissue engineering applications, fibrin must be reinforced, and there is a board range of nano-and other materials such as autogenous bone grafts, 20,21 allogenic bone grafts, 22,23 xenogeneic bone grafts, 24 metals, [25][26][27] ceramics, [28][29][30] …”

“…Moreover, they can easily fill irregular-shaped defects. Although fibrin possesses fascinating features, fibrin alone is not capable to heal bone defects, 26,152,169 and it is necessary to mix fibrin with other components such as biological bone grafts, osteoconductive biomaterials, osteogenic cells, and bioactive molecules.…”

“…In other words, fibrin alone did not improve the bone regeneration potential of Ti implants but served as a delivery vehicle for BMP-2 that improved the bone repair process. 26 Fibrin can also be employed to simultaneously deliver osteogenesis and angiogenesis growth factors when incorporated into porous metallic implants. 27 Some other researchers have argued that constructing 3D scaffolds of natural polymers on metallic implants, rather than providing a thin coating, resembles the architecture of the native bone matrix more closely.…”

Additive Manufacturing of Biomaterials, Tissues, and Organs

“…These structures also provide pore spaces, which could be used for drug delivery purposes, e.g., to facilitate tissue regeneration or combat infection. 70 Finally, lattice structures have huge adjustable surface areas that could be biofunctionalized 68 to achieve improved tissue regeneration performance 3,17 and antibacterial behavior.…”

Tailoring Bioengineered Scaffolds for Regenerative Medicine

“…In order to tailor the mechanical properties of cellular structured scaffolds, [14] designed metal scaffolds with high porosity (62-92%) to tailor both compressive strength (4.0-113.0 MPa) and elastic modulus (0.2-6.3 GPa), respectively, were comparable to trabecular and cortical bone. Porous titanium scaffolds were also investigated by van der Stok et al [15,16] for grafting large bone defects. Mechanical properties were tailored, whereas high porosity of the scaffold allowed the incorporation of colloidal gelatin gels for time-and dose-controlled delivery of dual growth factors (bone morphogenetic protein-2 (BMP-2) and/or fibroblast growth factor-2 (FGF-2)), promoting a quasi-full bone regeneration.…”