In situ bone regeneration with sequential delivery of aptamer and BMP2 from an ECM-based scaffold fabricated by cryogenic free-form extrusion

Abstract

In situ tissue engineering is a powerful strategy for the treatment of bone defects. It could overcome the limitations of traditional bone tissue engineering, which typically involves extensive cell expansion steps, low cell survival rates upon transplantation, and a risk of immuno-rejection. Here, a porous scaffold polycaprolactone (PCL)/decellularized small intestine submucosa (SIS) was fabricated via cryogenic free-form extrusion, followed by surface modification with aptamer and PlGF-2 123-144 *-fused BMP2 (pBMP2). The two bioactive molecules were delivered sequentially. The aptamer Apt19s, which exhibited binding affinity to bone marrow-derived mesenchymal stem cells (BMSCs), was quickly released, facilitating the mobilization and recruitment of host BMSCs. BMP2 fused with a PlGF-2 123-144 peptide, which showed “super-affinity” to the ECM matrix, was released in a slow and sustained manner, inducing BMSC osteogenic differentiation. In vitro results showed that the sequential release of PCL/SIS-pBMP2-Apt19s promoted cell migration, proliferation, alkaline phosphatase activity, and mRNA expression of osteogenesis-related genes. The in vivo results demonstrated that the sequential release system of PCL/SIS-pBMP2-Apt19s evidently increased bone formation in rat calvarial critical-sized defects compared to the sequential release system of PCL/SIS-BMP2-Apt19s. Thus, the novel delivery system shows potential as an ideal alternative for achieving cell-free scaffold-based bone regeneration in situ .

A Composite Deferoxamine/Black Phosphorus Nanosheet/Gelatin Hydrogel Scaffold for Ischemic Tibial Bone Repair

“…Some researchers reported that dense and mature newly-formed fibrous tissue and new blood vessel in H&E staining and Masson staining indicated better bone regeneration and angiogenesis. 48 , 49 …”

Osteogenic Response to Polysaccharide Nanogel Sheets of Human Fibroblasts After Conversion Into Functional Osteoblasts by Direct Phenotypic Cell Reprogramming

“…However, gaining bone regeneration at large bone defects parts is still challenging. Therefore, recently, genes and/or RNAi modified osteoinductive artificial scaffolds (Laird et al, 2021;Sun et al, 2021) and genetically arranged high functional cell seeded scaffolds (Sato et al, 2018;Gugliandolo et al, 2021;Jiang et al, 2021) have been considered as new upcoming bone regeneration strategies.…”

Integrated bioactive scaffold with aptamer‐targeted stem cell recruitment and growth factor‐induced pro‐differentiation effects for anisotropic meniscal regeneration

“…Aptamers exhibit high specificity and affinity for target ligands without inducing immunogenic or toxic effects. Compared to other targeting agents, such as antibodies, chemokines, GFs, and peptides, aptamers possess greater temperature and pH stability and exhibit a high circulation clearance rate 16,17 . Recently, researchers have sought to utilize aptamers as therapeutic agents for the recognition and capture of MSCs for tissue engineering applications.…”