CXCL chemokines-mediated communication between macrophages and BMSCs on titanium surface promotes osteogenesis via the actin cytoskeleton pathway.

The refined functional cell subtypes in the immune microenvironment of specific titanium (Ti) surface and their collaborative role in promoting bone marrow mesenchymal stem cells (BMSCs) driven bone integration need to be comprehensively characterized. This study employed a simplified co-culture system to investigate the dynamic, temporal crosstalk between macrophages and BMSCs on the Ti surface. The M2-like sub-phenotype of macrophages, characterized by secretion of CXCL chemokines, emerges as a crucial mediator for promoting BMSC osteogenic differentiation and bone integration in the Ti surface microenvironment. Importantly, these two cells maintain their distinct functional phenotypes through a mutually regulatory interplay. The secretion of CXCL3, CXCL6, and CXCL14 by M2-like macrophages plays a pivotal role. The process activates CXCR2 and CCR1 receptors, triggering downstream regulatory effects on the actin cytoskeleton pathway within BMSCs, ultimately fostering osteogenic differentiation. Reciprocally, BMSCs secrete pleiotrophin (PTN), a key player in regulating macrophage differentiation. This secretion maintains the M2-like phenotype via the Sdc3 receptor-mediated cell adhesion molecules pathway. Our findings provide a novel insight into the intricate communication and mutual regulatory mechanisms operating between BMSCs and macrophages on the Ti surface, highlight specific molecular events governing cell-cell interactions in the osteointegration, inform the surface design of orthopedic implants, and advance our understanding of osteointegration.

The anatomical feasibility of anterior intra- and extra-bifurcation approaches to L5-S1: an anatomic study based on lumbar MRI.

BACKGROUND CONTEXT: The anterior approach at L5-S1 has many advantages, however, vascular complications are challenging for spinal surgeons who may not be familiar with the variability of vascular anatomy. There are three different anterior approaches (intra-bifurcation approach and extra-bifurcation: left-, and right-sided prepsoas approaches) described in previous studies to respond to the variability of anterior vascular anatomy for reduction in vascular injury, while no guidance for the choice of approach preoperatively. PURPOSE: To analyze the anatomical feasibility of three anterior approaches to access the L5-S1 disc space according to a practical framework. STUDY DESIGN: Retrospective study. PATIENT SAMPLE: Lumbar magnetic resonance imaging (MRI) from patients who visited our outpatient clinic were reviewed, with 150 cases meeting the inclusion criteria. OUTCOME MEASURES: The following radiographic parameters were measured on axial T2-weighted MRI at the lower endplate of L5 and the upper endplate of S1: width of the vascular corridor, position of the left and right common iliac vein (CIV), and presence of perivascular adipose tissue (PAT). Moreover, we designed a safe line to evaluate the feasibility of left- and right-sided prepsoas approaches. Cases of lumbosacral transitional vertebrae were identified. METHODS: The feasibility of the intra-bifurcation approach was determined by the width of the vascular corridor, presence of PAT, and the position of the CIV. The feasibility of the prepsoas approach was determined by the relative position of the CIV to the safe line, presence of PAT, and the intersection point of the CIV and vertebral body. RESULTS: Sixty-eight percent, 64.7%, and 75.3% cases allowed the intra-bifurcation, left-, and right-sided prepsoas approach to L5-S1, respectively. The cases in this study had at least one of three anterior approaches to access L5-S1 disc space, and 74% of cases had more than one anatomical feasibility of anterior approach. The right-sided prepsoas approach was feasible in the majority of cases because of the vertical course of the right CIV with a significantly higher proportion of presence of PAT. Patients with lumbosacral transitional vertebrae (24 cases) may prefer the prepsoas approaches, and only six cases (25.0%) were determined to be feasible for the intra-bifurcation approach. CONCLUSIONS: Our study proposes a practical framework to determine whether the three different anterior approaches are feasible access at L5-S1. According to the framework, all cases had the anatomical feasibility of using an anterior approach to access L5-S1, and three-fourths of cases had a replaceable anterior approach when encountering intraoperative difficulties.

A self-assembled bilayer polypeptide-engineered hydrogel for spatiotemporal modulation of bactericidal and anti-inflammation process in osteomyelitis treatment.

BACKGROUND: Drug resistance of pathogens and immunosuppression are the main causes of clinical stagnation of osteomyelitis. The ideal treatment strategy for osteomyelitis is to achieve both efficient antibacterial and bone healing through spatiotemporal modulation of immune microenvironment. METHODS: In this study, a bilayer hydrogel based on genetically engineered polypeptide AC10A and AC10ARGD was prepared by self-assembly. Ag2S QDs@DSPE-mPEG2000-Ce6/Aptamer (AD-Ce6/Apt) was loaded in the top layer AC10A hydrogel (AA) for antibacterial, and bone marrow-derived mesenchymal stem cells (BMSCs) were loaded in the lower layer AC10ARGD hydrogel (MAR) for bone healing. The AD-Ce6/Apt can be released from the AA hydrogel to target S. aureus before bacterial biofilm formation and achieved significant bactericidal effect under irradiation with a 660 nm laser. Moreover, AD-Ce6/Apt can induce M1 type polarization of macrophages to activate the immune system and eliminate residual bacteria. Subsequently, BMSCs released from the MAR hydrogel can differentiate into osteoblasts and promote the formation of an anti-inflammatory microenvironment by regulating the M2 type polarization of macrophages. The bilayer AA-MAR hydrogel possessed good biocompatibility. RESULTS: The in vitro and in vivo results showed that the AA-MAR hydrogel not only realized efficient photodynamic therapy of S. aureus infection, but also promoted the transformation of immune microenvironment to fulfill the different needs of each stage, which ultimately improved bone regeneration and mechanical properties post-surgery. CONCLUSION: This work presents an approach for spatiotemporal modulation of immune microenvironment in the treatment of osteomyelitis.