Engineering Stem Cell Recruitment and Osteoinduction via Bioadhesive Molecular Mimics to Improve Osteoporotic Bone-Implant Integration

Abstract

For patients with osteoporosis, the therapeutic outcomes of osteoimplants are substantially affected by the impaired proliferation, migration, and osteogenic differentiation abilities of bone marrow mesenchymal stem cells (BMSCs). To improve bone-implant integration in osteoporotic condition, here we reported a one-step biomimetic surface strategy to introduce BMSC recruiting and osteoinductive abilities onto metallic osteoimplants. In our design, the bioadhesive molecular peptide mimic inspired by mussel foot proteins (Mfps) was used as molecular bridging for surface functionalization. Specifically, a BMSC-targeting peptide sequence (E7) and an osteogenic growth peptide (Y5) were grafted onto the titanium implant surfaces through a mussel adhesion mechanism. We found that a rational E7/Y5 feeding ratio could lead to an optimal dual functionalization capable of not only significantly improving the biocompatibility of the implant but also enabling it to recruit endogenous BMSCs for colonization, proliferation, and osteogenic differentiation. Mechanistically, the E7-assisted in situ recruitment of endogenous BMSCs as well as the enhanced interfacial osteogenesis and osteointegration was associated with activation of the C-X-C chemokine receptor type 4 (CXCR4) receptor on the cell surface and promotion of stromal cell-derived factor (SDF-1α) autocrine secretion. We anticipated that rational dual-functional surfaces through bioadhesive molecular mimics will provide a simple, effective, nonimmunogenic, and safe means to improve the clinical outcomes of intraosseous implants, especially under osteoporotic conditions.

Renal Endothelial Cell‐Targeted Extracellular Vesicles Protect the Kidney from Ischemic Injury

“…Compared to the antagonist or antibody of P‐selectin, PBP afforded unique advantages, including high‐throughput yields at a low cost benefiting from the contribution of the solid phase peptide synthesis technique and ease of conjugation or modification as required due to the relatively simplistic and well‐defined chemical structure of polypeptides. [ 10 ] Additionally, it has been proven that PBP has a remarkable P‐selectin binding specificity with high affinity, which provides sufficient strength for anchoring PBP‐EVs on the surface of injured ECs under the wall shear of hemodynamic flow. [ 10c ] Therefore, we rationalized that PBP not only enhanced the selective specificity of PBP‐EVs but also provided spatiotemporal convenience for PBP‐EVs to access into and penetrate the injured endothelial layer in injured kidneys, which demonstrated that PBP is a superior targeting ligand for EC‐targeted renal theranostics.…”

“…[ 10 ] Additionally, it has been proven that PBP has a remarkable P‐selectin binding specificity with high affinity, which provides sufficient strength for anchoring PBP‐EVs on the surface of injured ECs under the wall shear of hemodynamic flow. [ 10c ] Therefore, we rationalized that PBP not only enhanced the selective specificity of PBP‐EVs but also provided spatiotemporal convenience for PBP‐EVs to access into and penetrate the injured endothelial layer in injured kidneys, which demonstrated that PBP is a superior targeting ligand for EC‐targeted renal theranostics.…”

Mussel-Inspired Caries Management Strategy: Constructing a Tribioactive Tooth Surface with Remineralization, Antibiofilm, and Anti-inflammation Activity

“…This multifunctional binding ability makes polyphenol species an ideal “bridge” molecule between inorganic and organic phases. Polyphenols inspired by mussels have been used to modify or coat inorganic and metal surfaces to enhance HAP crystallization, biomineralization, bone regeneration, , and cell adhesion. , At the same time, there are many similarities in environment between mussels and human oral environment, such as saline conditions, dynamic changes in fluid flow, pH, and temperature, and exposure to microorganisms and enzymes, which cause mussel-inspired solutions to be considered for a variety of properties widely used in dental materials. For example, deposited tannin–Fe 3+ complexes adsorbed calcium and phosphate ions in artificial saliva to induce the remineralization of HAP crystals .…”

Bone-Targeting HUVEC-Derived Exosomes Containing miR-503-5p for Osteoporosis Therapy

“…Osteoporosis (OP) is a systemic bone disease characterized by reduced bone mass, damaged bone microstructure, and increased bone fragility, leading to a high risk of fractures. , The disease is more common in postmenopausal women and the elderly population, and with the population aging, the incidence of OP continues to rise, bringing serious burdens to society and families. , Excessive activity of osteoclasts causing increased bone resorption is an important pathological mechanism of OP . Therefore, osteoclast inhibitors (such as bisphosphonates and calcitonin) are commonly used in clinical practice to treat OP and have achieved certain effects .…”