Polycaprolactone Scaffolds for BONE Regeneration in Animal Models of Cranial Defects: A Systematic Review and Meta-Analysis

Polycaprolactone (PCL) is a biodegradable polymer widely used in bone tissue engineering; however, its regenerative performance in cranial defect models remains incompletely characterized. This systematic review and meta-analysis evaluated the effect of PCL scaffolds on bone regeneration in preclinical cranial defect models. PubMed, Embase, Web of Science, and Scopus were systematically searched, and eligible animal studies were selected according to predefined criteria. A total of 37 studies were included in the systematic review. Data on scaffold characteristics, animal models, and osteogenic outcomes were extracted, followed by random-effects meta-analysis and meta-regression to investigate potential sources of heterogeneity. PCL-based scaffolds significantly enhanced bone regeneration at one and two months post-surgery, with pooled mean differences of 1.68 (95% CI: 0.34–3.03; p = 0.01) and 5.60 (95% CI: 3.48–7.72; p < 0.00001), respectively. The treatment effect was greatest at two months but decreased at three months and was no longer statistically significant (MD = 2.22, 95% CI: −1.36–5.80; p = 0.22). Extreme between-study heterogeneity was observed across the time-point analyses, limiting the consistency and generalizability of the pooled estimates. Meta-regression identified animal species as a significant moderator at one month, accounting for 28.8% of the estimated heterogeneity, whereas follow-up duration and defect size were not significant moderators. Overall, PCL-based scaffolds demonstrate a beneficial but potentially time-dependent effect on bone regeneration, while their long-term regenerative performance remains uncertain.