Enhanced Bone Regeneration of Cortical Segmental Bone Defects Using Porous Titanium Scaffolds Incorporated with Colloidal Gelatin Gels for Time- and Dose-Controlled Delivery of Dual Growth Factors

Abstract

Porous titanium scaffolds are a promising class of biomaterials for grafting large bone defects, because titanium provides sufficient mechanical support, whereas its porous structure allows bone ingrowth resulting in good osseointegration. To reinforce porous titanium scaffolds with biological cues that enhance and continue bone regeneration, scaffolds can be incorporated with bioactive gels for time-and dose-controlled delivery of multiple growth factors (GFs). In this study, critical femoral bone defects in rats were grafted with porous titanium scaffolds incorporated with nanostructured colloidal gelatin gels. Gels were loaded with bone morphogenetic protein-2 (BMP-2, 3 mg), fibroblast growth factor-2 (FGF-2, 0.6 mg), BMP-2, and FGF-2 (BMP-2/FGF-2, ratio 5:1) or were left unloaded. GF delivery was controlled by fine tuning the crosslinking density of oppositely charged nanospheres. Grafted femurs were evaluated using in vivo and ex vivo micro-CT, histology, and three-point bending tests. All porous titanium scaffolds containing GF-loaded gels accelerated and enhanced bone regeneration: BMP-2 gels gave an early increase (0-4 weeks), and FGF-2 gels gave a late increase (8-12 weeks). Interestingly, stimulatory effects of 0.6 mg FGF-2 were similar to a fivefold higher dose of BMP-2 (3 mg). BMP-2/FGF-2 gels gave more bone outside the porous titanium scaffolds than gels with only BMP-2 or FGF-2, resulted in bridging of most defects and showed superior bone-implant integrity in three-point bending tests. In conclusion, incorporation of nanostructured colloidal gelatin gels capable of time-and dose-controlled delivery of BMP-2 and FGF-2 in porous titanium scaffolds is a promising strategy to enhance and continue bone regeneration of large bone defects.

Additively manufactured porous tantalum implants

“…In this experiment, eight rats have been implanted with a 6 mm porous Ta implant to reconstruct a critical-sized femoral bone defect. Since Ta has a high atomic 15 weight, it highly absorbs X-rays and it is therefore difficult to use standard evaluation techniques like radiographic or 3D CT follow-up as was performed in previous studies [83,84,87]. Nevertheless, implant fixation can still be observed from the presence of radiolucent properties are very small.…”

“…The unit cell used as the microarchitecture of these porous structures was a dodecahedron (Figure 1 B), with an average strut size of 150 µm and an average pore size of 500 µm, which resulted in an overall open porosity of ±80%. This specific unit cell was chosen in order to compare the obtained results with those of previous studies that used identical dodecahedron structures made by SLM out of Ti-6Al-4V ELI powder [83][84][85][86][87]. In this work, the same spherical pure Ta powder (chemical composition according to ISO 13782 [88], measured purity of 99.99% by ICP-MS) with particle size ranging from 10 µm to 25 µm as in [80] …”

“…Serum-supplemented Minimum Essential Medium (MEM-complete) was used as the cell culture medium. 9 For the functional in vivo evaluation of the open porous Ta implants, load-bearing segmental bone defects were used as described earlier [83,84,87]. In brief, a critical-sized femoral bone defect was grafted with a porous Ta implant in eight male Wistar rats.…”

The Static and Fatigue Behavior of AlSiMg Alloy Plain, Notched, and Diamond Lattice Specimens Fabricated by Laser Powder Bed Fusion

“…For example, in the field of biomedicine, there is a strong interest in the development of engineered lattice structures capable of mimicking the mechanical behavior of bones and providing strong bonding with surrounding tissues via the bone tissue ingrowth [5,6]. Moreover, the high surface/volume ratio of lattice structures makes them especially appropriate for high-efficiency heat exchangers [7] and catalyzers [8].…”

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.…”