C23-18 Hydroxyapatite Microspheres Are as Effective as Talc for Pleurodesis in a Porcine Model

Rationale Talc is effective for pleurodesis, but the particles become lifelong foreign bodies, are contaminated with lead, and have been associated with acute lung injury, chronic chest pain and complications with subsequent thoracic surgeries or lung transplantation. Our goal is to develop commercially available bone-like hydroxyapatite microspheres (HAM) as a biodegradable, contaminant free alternative to talc for pleurodesis. In a mouse model, HAM induces pleurodesis comparable to talc, and is cleared by recruited monocyte derived osteoclast-like cells within two months (Tanaka et al, JCI Insight. 2025). To further assess the safety and efficacy of HAM pleurodesis in a larger animal species with a pleural structure that is more similar to humans, we tested GMP-grade sintered (i.e.-baked @ >1000 °C) HAM (HAM-S) and non-sintered HAM (HAM-NS) in a porcine pleurodesis model. Methods Saline, HAM-S, HAM-NS, or talc (Steritalc™) were administered by thoracoscopic poudrage into the right thoracic cavity of anesthetized pigs (n = 3/group), using a pressurized powder blower Talcair™ to generate a fine mist. Serum markers of inflammation and ultrasound assessment of lung sliding were obtained on day 0, 7, and 28 post instillation. Animals were sacrificed on day 28, and pneumothorax volume was determined by quantitative cone beam CT after multiple passes of a spinal needle into the right hemothorax. Pleural adhesions were macroscopically scored, and histological analyses were performed to assess the extent of pleural thickening, fibrosis, and inflammatory infiltration. Results HAMs-NS and talc produced strong and consistent pleural adhesions, whereas HAMs-S and saline induced minimal or no adhesion. The pigs tolerated the procedure well, and there was no elevation serum inflammatory markers on days 7 or 28. Loss of lung sliding by day 7 was observed in most animals given HAM-NS or talc, and persisted through day 28, consistent with early and durable pleural symphysis. After sacrifice and induction of pneumothorax, the volume of air in the pleural space was markedly reduced in the HAM-NS and talc groups compared to HAM-S and saline groups. Histologically, intrapleural HAM-NS and talc produced marked pleural thickening with dense collagen deposition on Masson’s trichrome staining, whereas HAM-S and saline produce little or no inflammation or fibrosis. Conclusion In a porcine model, HAM-NS induced pleurodesis comparable to talc, based on loss of lung sliding, marked pleural thickening, intense adhesion formation and reduction in the volume of induced pneumothorax. Future studies will refine this approach toward future clinical application of HAM pleurodesis.