Tissue Integration Of Porous Polyhema Scaffold

Purpose: To maximize mass transport into biomaterial scaffolds for regenerative medicine, in vivo diagnostics, therapeutics, and cell delivery. We utilized matrix morphology to encourage long-term tissue integration. Methods: We implanted 1cm-diameter poly-hydroxyethylmethacrylate (pHEMA) disks with 40 and 80µm nominal interconnected pores into rat subcutis. Solid pHEMA, silicone, and cotton disks were also implanted. Microvessel density and total cellularity were histologically quantified in 50µm-wide zones both into the implants and into the adjacent tissues. Results: One week after implantation, the microvessel density closest to the interface was 74±8/mm2 (mean±SEM) for the 80µm pHEMA and 28±8/mm2 for the 40µm pHEMA. The rate of vascularization was greater in 80µm pHEMA, with higher vascular density in the material and adjacent tissues one week and one month post-implantation (p<0.001). After two months, vascular ingrowth was similar for both 40 and 80µm pHEMA (maximum = 155±32/mm2 and 182±43/mm2, respectively). Solid pHEMA and silicone exhibited no vascular ingrowth. At two months, the microvessel density in the 0-50µm adjacent tissue was 203±11/mm2, compared to 101±15/mm2 for the 40 µm pHEMA; 60±16/mm2 for the solid pHEMA; and 24±7/mm2 for silicone. All materials except 80µm pHEMA showed a narrow margin of significantly reduced vascularity at the implant-tissue interface. Total cellularity in the 0-50µm tissue adjacent to 80µm pHEMA was 7736±1011/mm2 after one week; 7582±1129/mm2 after one month; and 4498±497/mm2 after two months. Using real-time ultrasonic microscopy, the microshearing that can disrupt microvessel formation was observed to decrease as tissue integrated into the pores. Conclusion: Mass transport is key to successful tissue engineered platforms. Robust tissue integration, particularly at the critical implant-tissue interface, makes open interconnected-pore pHEMA an excellent morphology for scaffolds in regenerative medicine. Grant Funding Source: Supported by DARPA grants W911NF-11-1-0119 and HR0011-13-2-0003 and Duke Univ Photonics Institute