Bar Assaf, Kryukov Olga, Cohen Smadar
The Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
Regenerative Medicine and Stem Cell (RMSC) Research Center, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
Gels. 2022 Nov 25;8(12):769. doi: 10.3390/gels8120769.
Cardiac tissue engineering has emerged as a promising strategy to treat infarcted cardiac tissues by replacing the injured region with an ex vivo fabricated functional cardiac patch. Nevertheless, integration of the transplanted patch with the host tissue is still a burden, limiting its clinical application. Here, a bi-functional, 3D bio-printed cardiac patch (CP) design is proposed, composed of a cell-laden compartment at its core and an extracellular vesicle (EV)-laden compartment at its shell for better integration of the CP with the host tissue. Alginate-based bioink solutions were developed for each compartment and characterized rheologically, examined for printability and their effect on residing cells or EVs. The resulting 3D bio-printed CP was examined for its mechanical stiffness, showing an elastic modulus between 4-5 kPa at day 1 post-printing, suitable for transplantation. Affinity binding of EVs to alginate sulfate (AlgS) was validated, exhibiting dissociation constant values similar to those of EVs with heparin. The incorporation of AlgS-EVs complexes within the shell bioink sustained EV release from the CP, with 88% cumulative release compared with 92% without AlgS by day 4. AlgS also prolonged the release profile by an additional 2 days, lasting 11 days overall. This CP design comprises great potential at promoting more efficient patch assimilation with the host.
心脏组织工程已成为一种有前景的策略，通过用体外构建的功能性心脏补片替代受损区域来治疗梗死的心脏组织。然而，移植补片与宿主组织的整合仍然是一个难题，限制了其临床应用。在此，提出了一种双功能的3D生物打印心脏补片（CP）设计，其核心为载细胞隔室，外壳为载细胞外囊泡（EV）隔室，以促进CP与宿主组织更好地整合。针对每个隔室开发了基于藻酸盐的生物墨水溶液，并对其进行了流变学表征，检测了其可打印性以及对驻留细胞或EV的影响。对所得的3D生物打印CP进行了机械刚度检测，打印后第1天其弹性模量在4-5 kPa之间，适合移植。验证了EV与硫酸藻酸盐（AlgS）的亲和结合，其解离常数与EV与肝素的解离常数相似。壳层生物墨水中加入AlgS-EV复合物可使EV从CP持续释放，到第4天，累积释放率为88%，而未添加AlgS时为92%。AlgS还将释放曲线延长了2天，总共持续11天。这种CP设计在促进补片与宿主更高效地同化方面具有巨大潜力。
