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Abstract In pursuit of a suitable scaffold material for cardiac valve tissue engineering applications, an acellular, electrospun, biodegradable polyester carbonate urethane urea (PECUU) scaffold was evaluated as a pulmonary valve leaflet replacement in vivo
. In sheep (n = 8), a single pulmonary valve leaflet was replaced with a PECUU leaflet and followed for 1, 6, and 12 weeks. Implanted leaflet function was assessed in vivo by echocardiography. Explanted samples were studied for gross pathology, microscopic changes in the extracellular matrix, host cellular re‐population, and immune responses, and for biomechanical properties. PECUU leaflets showed normal leaflet motion at implant, but decreased leaflet motion and dimensions at 6 weeks. The leaflets accumulated α‐SMA and CD45 positive cells, with surfaces covered with endothelial cells (CD31+). New collagen formation occurred (Picrosirius Red). Accumulated tissue thickness correlated with the decrease in leaflet motion. The PECUU scaffolds had histologic evidence of scaffold degradation and an accumulation of pro‐inflammatory/M1 and anti‐inflammatory/M2 macrophages over time in vivo. The extent of inflammatory cell accumulation correlated with tissue formation and polymer degradation but was also associated with leaflet thickening and decreased leaflet motion. Future studies should explore pre‐implant seeding of polymer scaffolds, more advanced polymer fabrication methods able to more closely approximate native tissue structure and function, and other techniques to control and balance the degradation of biomaterials and new tissue formation by modulation of the host immune response. -
Polymeric coatings can provide temporary stability to bioresorbable metallic stents at the initial stage of deployment by alleviating rapid degradation and providing better interaction with surrounding vasculature. To understand this interfacing biocompatibility, this study explored the endothelial-cytocompatibility of polymer-coated magnesium (Mg) alloys under static and dynamic conditions compared to that of non-coated Mg alloy surfaces. Poly (carbonate urethane) urea (PCUU) and poly (lactic-co-glycolic acid) (PLGA) were coated on Mg alloys (WE43, AZ31, ZWEKL, ZWEKC) and 316L stainless steel (316L SS, control sample), which were embedded into a microfluidic device to simulate a vascular environment with dynamic flow. The results from attachment and viability tests showed that more cells were attached on the polymer-coated Mg alloys than on non-coated Mg alloys in both static and dynamic conditions. In particular, the attachment and viability on PCUU-coated surfaces were significantly higher than that of PLGA-coated surfaces of WE43 and ZWEKC in both static and dynamic conditions, and of AZ31 in dynamic conditions (P<0.05). The elementary distribution map showed that there were relatively higher Carbon weight percentages and lower Mg weight percentages on PCUU-coated alloys than PLGA-coated alloys. Various levels of pittings were observed underneath the polymer coatings, and the pittings were more severe on the surface of Mg alloys that corroded rapidly. Polymer coatings are recommended to be applied on Mg alloys with relatively low corrosion rates, or after pre-stabilizing the substrate. PCUU-coating has more selective potential to enhance the biocompatibility and mitigate the endothelium damage of Mg alloy stenting.more » « less
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Abstract For degradable magnesium (Mg) alloy‐based stents it would be desirable to delay early corrosion to maintain mechanical strength. Similarly, early after stent placement reduced thrombogenicity is an important feature, while chronically, endothelial cell adhesion and vessel integration are desirable. In this study, surface eroding polymers of amino‐grafted poly(1,3‐trimethylene carbonate) (PTMC‐NH2) and PTMC‐NH2combined with sulfobetaine bearing polymer PSB (PTMC‐NHCO‐PSB) are developed, and these polymers are covalently attached onto 6‐phosphonohexanoic acid (PHA)‐coated AZ31 Mg alloy surfaces in sequence. In vitro degradation testing in ovine plasma shows PTMC, PTMC‐NH2, and PTMC‐NHCO‐PSB cast films experience a gradual thickness and mass loss with maintenance of smooth surfaces, confirming surface erosion behavior. The PTMC‐NH2polymer is firmly bound to the PHA‐modified AZ31 surface and demonstrates a resistance to peeling. PTMC, PTMC‐NH2, and PTMC‐NHCO‐PSB coated AZ31 have a lower corrosion rate versus polylactide‐
co ‐glycolide coated and untreated AZ31. PTMC‐NHCO‐PSB coated AZ31 inhibits platelet deposition and smooth muscle cell adhesion and growth, but after 2‐week immersion in plasma, this surface supports endothelial cell adhesion and growth. These results suggest PTMC‐NHCO‐PSB surface eroding coating offers a means of controlling corrosion while providing a temporally varying bio‐functionality for biodegradable vascular stent applications.