| Objective:The purpose of this study was to prepare biodegradable lovastatin delivery scaffolds composed of polylactic acid-co-glycolic acid (PLGA),and preliminarily evaluate their feasibility as cardiac tissue engineering scaffolds.Methods:PLGA scaffolds and lovastatin-PLGA scaffolds were prepared by thermal-induced phase separation technique. The structure of the samples were analyzed by scanning electron microscopy. Their transversal and longitudinal suture tension were tested respectively. Their degradation properties were tested by hydrolytic degradation test. After buliding subcutaneous embedding models, their histocompatility were studied in1,4weeks respectively by H&E staining. Bone marrow derived mesenchymal stem cells(BMSCs) were harvested, cultured and seeded in the scaffolds of the3rd generation cells with a concentration of4X10/cm2.The growing situation of cells were detected by Hoechst staining and scanning electron microscopy. Results:1,Lovastatin-PLGA scaffolds had a form of microtubules orientation-structured full of pores in scanning electron microscopy. Their internal pores were interconnected and favor of cell growth.2,The mechanical properties of lovastatin-PLGA scaffolds were stable. Their longitudinal suture tension were similar to PLGA scaffolds (4.8±0.4N vs5.0+0.5N, p>0.05)。3,The degradation of lovastatin-PLGA scaffolds were accelerated from the6th week and their mass loss lower than PLGA scaffolds (78.8±0.8%vs81.9±1.6%, P<0.01) beginning from the8th week.4,Lovastatin-PLGA scaffolds did not reveal significant inflammatory response in1and4weeks after establishment of subcutaneous embedding models. The internal of scaffolds were full of blood vessels and rat fibroblast cells grew along the orientation-structured scaffolds.5,BMSCs were stack-like growing and distributed among the scaffolds by the test of Hoechst staining and scanning electron microscopy.Conclusions:.1,Lovastatin-PLGA scaffolds meet the morphology and mechanical properties requirements of cardiac tissue engineering. In addition, they have degradation and drug delivery properties. 2,Lovastatin-PLGA scaffolds have good histocompatility and BMSCs were grew well on them. They can be safely transplanted in vivo as scaffolds of cardiac tissue engineering. Objective:The purpose of this study was to investigate the efficacy and possible mechanisms of BMSCs transplantation combined with lovastatin-PLGA scaffolds for treatment of myocardial infarction(MI) in rats.Methods:In Sprague-Dawley rats, the establishment of myocardial infarction model was conducted by left anterior coronary artery ligation.3weeks after the first operation,The qualified female animals were divided randomly to5groups. In control group,the animals only underwent re-thoracotomy. PLGA group(P group) and lovastatin-PLGA group(LP group) received corresponding scaffolds transplantation on the MI zone respectively. After BMSCs seeded on scaffolds, tissue engineering-PLGA group(TP group) and tissue engineering-lovastatin-PLGA group (TLP group) were transplanted on the infarction zone respectively.1,4and8weeks after the second operation, the echocardiogram (UCG) was used to evaluate the cardiac remodeling and heart function. Myocardial fibrosis was tested by Masson staining. The expression of TGF-β1,MMP-2,9,TNF-α and the angiogenesis on MI zone were estimated by the immunohistochemistry. Ordinary polymerase chain reaction(PCR) was employed to detect BMSCs survival. Myogenic differentiation was estimated by the immunofluorescence staining.Results:Compared with control group in the end of the experiment, the animals of other groups showed improved heart function assessed by left ventricular ejection fraction, left ventricular fractional shortening, left ventricular end systolic pressure and±dp/dtmax(P<0.01).In addition, the heart function improved significantly in TLP group compared with other experimental group(P<0.05). Compared with other groups, Masson staining showed that the myocardial fibrosis is lighter and immunohistochemistry study demonstrated the expression of TGF-(31,MMP-2,9,TNF-a decreased significantly companied with the angiogenesis increased significantly (P<0.01) in TLP group. Both in TP group and TLP group,Y chromosome gene was detected and a small amount of cells were found differentiated to cardiomyocytes。Conclusions:TLP scaffolds can inhibit ventricular remodeling, inflammatory response and promote angiogenesis in MI zone. BMSCs can survive after its transplantation. Therefore, TLP scaffolds transplantation can improve heart function after MI in rats.
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