# Recombinant Proteins-Based Strategies in Bone Tissue Engineering
## 5 Recombinant Human BMPs in Bone Tissue Engineering
All concentrations of both rh BMPs tested were able to significantly induce _mRNA_ levels of Runx2, COL1a2 and OCN, but only rhBMP9 significantly upregulated ALP _mRNA_ levels (up to eightfold), and ALP staining (up to 25-fold). Subsequent work by members of the same group with a fibrin sealant as a carrier system of rhBMP-9 demonstrated its high osteogenic potential [47]. A very recent study has investigated the bone formation capacity of rhBMP-2 absorbed in a collagen sponge (ACS), and proposed that these scaffolds could be a successful strategy in patients with osteonecrosis of the jaw [48]. Another recent strategy has exploited the ability of glycosaminoglycan hydrogel scaffolds (CS-GAG) to cell encapsulation, providing an extracellular matrix (ECM)-like microenvironment. In a very original experiment, MSCs cells were induced to overexpress rhBMP-2, and were then seeded in a CS-GAG hydrogel. The hydrogels were delivered in electrospun polycaprolactone nanofiber meshes, so that the release of rhBMP2 would occur locally as required at the bone defect. When applied to a model of critical bone injury, it was efficient to heal the latter, in terms of increased bone volume, strength, and stiffness of newly formed bone [49]. Moreover, synthetic PEG-based hydrogels, as biocompatible and tunable cell niches, were engineered to fast release platelet-derived growth factor (PDGF-BB) and sustained delivery of low-dose BMP-2. These hydrogels promoted bone formation, enhancing the effect of BMP-2 [50]. In summary, although BMP-2 and BMP-9 actively participate in processes related to bone formation and repair (Figure 1), due to physiological, cost, and adverse reaction reasons, their direct delivery at the sites of injury is inappropriate. Therefore, a variety of maneuvers have been developed, including synthesis of chimeric BMP-containing proteins or to promote their binding to scaffolds for their controlled release, to make them useful as bone tissue engineering strategies (Table 1). \begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Type of Scaffold** & **In Vitro** & **In Vivo** & **Results** & **References** \\ \hline Collagen and BMP2 & hMSC & Cranial defects in rats &
\begin{tabular}{c} Satisfactory activity of alkaline \\ phosphatase. Histopathological \\ study and nuclear magnetic \\ resonance imaging repair of the \\ upper bone defect with the \\ association of BMP-2 \\ insignificant inflammation. \\ \end{tabular} & \multirow{4}{*}{[41]} \\ Collagen and BMP2 & & & \\ \cline{3-4}  & & & \\ \cline{3-4}  & & & \\ \cline{3-4}  & & & \\ \cline{3-4}  & & & \\ \cline{3-4}  & & & \\ \cline{3-4}  & & & \\ \cline{3-4}  & & & \\ \cline{3-4}  & & & \\ \cline{3-4}  & & & \\ \cline{3-4}  & & & \\ \cline{3-4}  & & & \\ \hline Mineralized recombinant & & & \\ \cline{3-4}  & & & \\ \cline{3-4}  & & & \\ \cline{3-4}  & & & \\ \cline{3-4}  & & & \\ \cline{3-4}  & & & \\ \cline{3-4}  & & & \\ \cline{3-4}  & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Outstanding work applying recombinant bone morphogenetic proteins ( BMPs) in tissue engineering strategies.