ALP x BMP2 x RUNX2

This study aimed to investigate the osteogenic function of polyetheretherketone (PEEK) scaffolds modified with bone morphogenetic protein 2 (BMP2) and its possibility for orbital fracture repair. The 3D-printed PEEK sheets were combined with BMP2-loaded hyaluronic acid hydrogel (HAH) to fabricate PEEK-BMP2-HAH composite scaffolds. Bone marrow mesenchymal stem cells (BMSCs) were seeded onto PEEK or PEEK-BMP2-HAH scaffolds. Cell adhesion and cell proliferation were measured by transmission electron microscopy and CCK-8 assay. Alkaline phosphatase (ALP) chromogenic, alizarine red S staining, and PCR analysis of Runt-related transcription factor 2 (Runx2), collagen-I (Col-I), Osterix, and osteopontin (OPN) were performed to assess osteogenic activity. The rat orbital fracture defect model is proposed for evaluating the biocompatibility, osteogenic integration, and functional recovery of PEEK orbital implants. Compared with PEEK, cell adhesion and cell proliferation were increased in PEEK-BMP2-HAH scaffolds. ALP activity and mineralized nodule formation were increased in PEEK-BMP2-HAH scaffolds than that in PEEK the mRNA expression of Runx2, Osterix, Col-I and OPN was increased on PEEK-BMP2-HAH scaffolds than that on PEEK at 14 d of osteogenic induction. Besides, a bone defect animal model revealed that BMP2-HAH-modified PEEK scaffolds could effectively facilitate the repair of the orbital bone defect, with increased expression of OPN and Runx2. BMP2-loaded HAH effectively increased adhesion, proliferation, and osteogenic differentiation of BMSCs on PEEK. PEEK-BMP2-HAH scaffolds are expected to become new materials for orbital fracture repair.

After tooth extraction, alveolar bone absorbs unevenly, leading to soft tissue collapse, which hinders full regeneration. Bone loss makes it harder to do dental implants and repairs. Inspired by the biological architecture of bone, a deformable SIS/HA (Small intestinal submucosa/Hydroxyapatite) composite hydrogel coaxial scaffold was designed to maintain bone volume in the socket. The SIS/HA scaffold containing GL13K as the outer layer, mimicking compact bone, while SIS hydrogel loaded with bone marrow mesenchymal stem cells-derived exosomes (BMSCs-Exos) was utilized as the inner core of the scaffolds, which are like soft tissue in the skeleton. This coaxial scaffold exhibited a modulus of elasticity of 0.82 MPa, enabling it to adaptively fill extraction sockets and maintain an osteogenic space. Concurrently, the inner layer of this composite scaffold, enriched with BMSCs-Exos, promoted the proliferation and migration of human umbilical vein endothelial cells (HUVECs) and BMSCs into the scaffold interior (≈3-fold to the control), up-regulated the expression of genes related to osteogenesis (BMP2, ALP, RUNX2, and OPN) and angiogenesis (HIF-1α and VEGF). This induced new blood vessels and bone growth within the scaffold, addressing the issue of low bone formation rates at the center of defects. GL13K was released by approximately 40.87 ± 4.37 % within the first three days, exerting a localized antibacterial effect and further promoting vascularization and new bone formation in peripheral regions. This design aims to achieve an all-around and efficient bone restoration effect in the extraction socket using coaxial scaffolds through a dual internal and external mechanism.

Osteoporosis, characterized by an increased risk of fractures, represents a significant global public health issue. Natural compounds have emerged as promising candidates for addressing this condition. Shikonin, derived from Lithospermum erythrorhizon as a purple-red naphthoquinone pigment, exhibits a diverse array of biological activities, including antibacterial, anti-inflammatory, and anticancer properties. Despite the well-documented bone-protective properties of shikonin, the precise molecular mechanisms underlying its role in the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) into osteoblasts, along with its implications on angiogenesis, are not fully elucidated. Our study showcases shikonin's ability to stimulate the differentiation of BMSCs into osteoblasts, leading to an upregulation of osteoblast-specific marker genes such as OC, Runx2, BMP2, and ALP. Furthermore, shikonin intervention triggers the upregulation of phosphorylation of p38, ERK, and JNK in the MAPK signaling pathway. Furthermore, shikonin has been shown to enhance the migration and angiogenic capabilities of human umbilical vein endothelial cells (HUVECs). Notably, the augmentation of HUVEC migration by shikonin can be counteracted by the addition of a JNK inhibitor. Furthermore, our findings indicate that shikonin effectively improves osteoporosis in aged mice by promoting osteoblast differentiation. In summary, our study elucidates the molecular mechanisms through which shikonin exerts its beneficial effects in the treatment of osteoporosis, highlighting its potential as a novel therapeutic option for both the prevention and management of this condition.