Bioprinted Scaffold Remodels the Neuromodulatory Microenvironment for Enhancing Bone Regeneration

Abstract

Herein, a 3D bioprinted scaffold is proposed, containing a calcitonin gene‐related peptide (CGRP) and the β‐adrenergic receptor blocker propranolol (PRN) as a new method to achieve effective repair of bone defects. By leveraging the neuromodulation mechanism of bone regeneration, CGRP and PRN loaded mesoporous silica nanoparticles are added into a hybrid bio‐ink, which initially contains gelatin methacrylate, Poly (ethylene glycol) diacrylate and bone marrow mesenchymal stem cells (BMSCs). Subsequently, the optimized bio‐ink is used for 3D bioprinting to create a composite scaffold with a pre‐designed micro‐nano hierarchical structure. The migration and tube formation of human umbilical vein endothelial cells (HUVECs) can be promoted by the scaffold, which is beneficial to the formation of a new capillary network during the bone repair process. With the release of CGRP from the scaffold, the secretion of neuropeptides by sensory nerves is simulated. Meanwhile, the release of PRN can inhibit the binding process of catecholamine to β‐adrenergic receptor, co‐promoting the osteogenic differentiation of BMSCs with CGRP and silicon ions, which will effectively enhance bone repair of a critical‐sized cranial defect in a rat model. In conclusion, this study provides a promising strategy for bone defect repair by understanding the neuromodulatory mechanisms during bone regeneration.

Chirality-biased protein expression profile during early stages of bone regeneration

“…The cranial bone defect model was created in healthy 5-week old SD rats ( Wang et al, 2022 ; Guo and He, 2023 ). All protocols and procedures are compliant with the guidelines prescribed by the Association for Assessment and Accreditation of Laboratory Animal Care, approved by the Peking University Health Centre Institutional Animal Care and Use Committee and Peking University Health Centre Ethics Committee (LA2019320).…”

Emerging roles of nerve‐bone axis in modulating skeletal system

“…As a result, the controlled release of CGRP and PRN collaboratively enhances MSC differentiation via neuromodulation. 208 Notably, a functionalized 3D-printed silk-hydroxyapatite (HAP) scaffold loaded with NGF has been validated to enhance neurite extension, coupled with the release of BMP2 and VEGF to amplify the expressions of osteogenic differentiation genes. 209 NGF has also been loaded into a GelMA/alginate methacrylate (AlgMA) hydrogel bioprinted system containing laponite (Lap), designed for engineered bone regeneration, promoting CGRP expression, and creating a conducive microenvironment for osteogenesis.…”

Silicon-containing nanomedicine and biomaterials: materials chemistry, multi-dimensional design, and biomedical application

“…He's group conducted a series of studies on the construction of MSN-incorporated bone scaffolds, including hydrogels, 515–517 electrospinning membranes, 518,519 phase-separation porous scaffolds, 520 and 3D-printing scaffolds. 521–524 In their design, MSNs were adopted as nanocarriers of diverse biological agents, ranging from small molecule drugs (osteogenic/angiogenic/immunosuppressive/anti-inflammation effects), bone-forming peptides, and small RNA. Due to the sustained and controlled release of these agents, together with the bioactivity of the degraded silicate ions from MSNs, the composite scaffolds exhibited both high osteogenic activity and synergistic functionalities for advanced bone tissue engineering.…”