"Bone tissue regeneration (BTR) has been trying to mimic the bone environment in biofabricated platforms. Given the complex bone metabolism, creating a functional, differentiated and biologically compatible platform that stimulates tissue formation in an autonomous way is currently a challenge . Therefore, the development of multifunctional micro-platforms easy to produce and to translate into the clinic while promoting BTR is a top priority. In this work, we boosted a recently developed platform fabricated in combination with metal coordination and gelling properties of gelatin , providing a suitable microenvironment for applications in BTR.
Using gelatin modified with two different catechol analogues (Hydroxypiridinone-HOPO, and Dopamine-DA) as building blocks on the creation of liquefied protein-based microcapsules (mCap), we encapsulated bone-marrow human mesenchymal stem cells (BM-hMSC) using the electrospray technique. The presence of HOPO allowed the formation of the micro-hydrogel shell through metal coordination, while DA was inserted by its affinity for calcium ions allowing the mineralization of the system by deposition of calcium-phosphate crystals (e.g. hydroxyapatite-HA) .
With this strategy, we created the desired microenvironment for mineralization and osteogenesis without the demand of osteogenic inducers. With BM-hMSCs organizing themselves inside the inner wall of the gelatin shell, mCap created an encouraging environment for cell communication and differentiation. The inclusion of DA into the system prompted accelerates the differentiation process, with osteoblastic stages being reached in early periods of culture. The prompt differentiation into osteoblasts might be related to the bioactive properties of the mCap, autonomously promoting the deposition of HA crystal. A more detailed analysis revealed the formation of a dense mantle in the interior of this enclosed system, exposing matrix deposition covering osteoblasts. The fact that osteoblast can merge within the new bone matrix suggests that this micro-platform can potentiate the formation of osteocytes, supporting this as a suitable biomimetic platform to closely resemble bone morphology. Therefore, the achieved bone-like microcapsules are a promising bioengineering platform that induce autonomously and in a fast way osteogenesis. By recreating part of the bone cellular microenvironment and architecture, this platform can be explored to bioengineering more closely the bone niche, addressing a variety of bone defects.