A pre-clinical analysis of immunohistochemistry for bone regeneration and angiogenesis with nanocomposite gels - A systematic review and meta-analysis.

Abstract

Nanocomposite gel scaffolds is a promising technique for bone reconstructing in maxillofacial and orthopedic surgeries with the advantage of minimizing invasiveness and donor site morbidity. This review examines the potential of nanofiber hydrogels as scaffolds for bone regeneration and angiogenesis in critical-size defects based on histomorphometric and immunohistochemistry analysis while carefully considering the need for optimizing it with digital spatial transcriptomics in future bone research. Various scientific databases such as PubMed, Web of Science, ProQuest, and Embase were searched for pre-clinical studies published between 2000 and 2025, which focused on effects of bone regeneration and angiogenesis based on immunohistochemistry. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed for gathering data. The ARRIVE checklist and Funnel plot analysis were utilized to evaluate the quality of the included studies. A meta-analysis was conducted to identify the true effects and biases involved in various studies. Twenty five articles were included for quantitative analysis. The pooled standardized mean difference (SMD = 4.52, 95% CI [3.29, 5.75]) strongly favors the experimental group indicating a significant improvement in bone regeneration outcomes. The diversity of methodologies and scaffold compositions used, showcases the broad applicability of these advanced biomaterials across different animal models supporting regeneration of bone. While immunohistochemistry is an established tool in its discoveries in skeletal defects, spatial transcriptomics has started its evolution as a cornerstone technology for future research in bone disorders.