Engineering injectable composite scaffolds for enhanced bone healing: Integration of stem cells, hydrogels, and microspheres

• This study develops a composite scaffold with hydrogels, microspheres, and stem cells for bone defect repair. • The scaffold enhances bone regeneration and improves bone density and trabecular structure. • It reduces inflammation and supports bone repair. • The material is injectable and suitable for minimally invasive treatments. • The scaffold shows strong safety and efficacy in animal studies, with potential for clinical use. Bone defects, often resulting from trauma, infections, or congenital conditions, represent a critical clinical challenge, as they impede natural healing and significantly impact patients’ quality of life. Traditional bone grafting methods, such as autografts and allografts, are limited by donor availability, immune rejection, and infection risks, highlighting the need for alternative solutions. In this study, we explore the use of a bionic hydrogel (CulX II) encapsulating PDLLA microspheres loaded with human umbilical cord mesenchymal stem cells (hUC-MSCs) as a promising strategy for bone defect repair. This innovative composite combines the biocompatibility and regenerative capabilities of hydrogels, the mechanical reinforcement from PDLLA microspheres, and the osteogenic and anti-inflammatory properties of hUC-MSCs. We systematically characterize the physical and chemical properties of the composite, assess its biocompatibility, and investigate its osteogenic and anti-inflammatory effects in vitro and in vivo using a rat femoral defect model. Our findings demonstrate that demonstrates its ability to stimulate new bone formation while effectively regulating inflammatory responses, positioning it as a promising option for improving bone regeneration in clinical settings.