Survivors from myocardial infarction (MI) eventually develop heart failure due to the post-infarct ventricular remodeling which could not be suppressed by existing treatments. Currently, coronary heart disease has become the major cause of heart failure instead of rheumatic heart disease in China. For this reason, seeking effective treatment to prevent post-infarct ventricular remodeling is urgent. Intramyocardial injection of hydrogels as a new strategy for MI treatment has made great progress recently. This review discusses the principle, present status, mechanisms and prospects of injectable hydrogel therapies for MI.
ObjectiveTo fabricate an injectable composite bone substitute with hyaluronic acid (HA) and calcium sulfate and to evaluate the biocompatibility and effect of the composite on cell proliferation, osteogenic differentiation in vitro and osteogenic capability in vivo. MethodsCalcium sulfate powder was mixed with HA solution, cross-linked HA solution, and phosphate buffer solution (PBS) in a ratio of 2∶1 (W/V) to get composites of CA+HA, CA+HAC, and CA. The standard extracts from above 3 materials were prepared according to ISO10993-5, and were used to culture mouse MC3T3-E1 cells. The composite biocompatibility and cell proliferation in different concentrations of extract were tested with cell counting kit-8 (CCK-8). The cells were cultured with standard medium as a control. The optimal concentration was selected for osteogenic differentiation test, and ELISA Kit was used to determine the alkaline phosphatase (ALP), collagen type I (COL-I), and osteocalcin (OCN). The femoral condylar bone defect was made on New Zealand white rabbits and repaired with CA+HA, CA+HAC, and CA. Micro-CT was done to evaluate new bone formation with bone volume/tissue volume (BV/TV) ratio at 6 and 12 weeks. HE staining was used to observe bone formation. ResultsCA+HA and CA+HAC were better in injectability and stability in PBS than CA. The biocompatibility test showed that absorbance (A) value of CA group was significantly lower than that of control group (P<0.05) at 6, 12, and 24 hours after culture, but no significant difference was found inA values between CA+HA group or CA+HAC group and control group (P>0.05). The proliferation test showed 25% and 50% extract of all 3 materials had significantly higherA value than control group (P<0.05). For 75% and 100% extract, only CA+HA group had significantly higherA value than control group (P<0.05). And 50% extract was selected for osteogenic differentiation test. At 14 and 21 days, ALP, COL-I and OCN concentrations of CA+HA group and CA+HAC group were significantly higher than those of CA group and control group (P<0.05). Micro-CT results showed higher BV/TV in CA+HA group and CA+HAC group than CA group at 6 and 12 weeks (P<0.05), but no significant difference was found between CA+HA group and CA+HAC group (P>0.05). HE staining revealed that a little bone tissue was seen in CA+HA group and CA+HAC group, but there was no bone formation in CA group at 6 weeks; more streak bone tissue in CA+HA group and CA+HAC group than CA group at 12 weeks. ConclusionComposites prepared with calcium sulfate and HA or with cross-linked HA are stable, injectable, and biocompatible. The materials have excellent effect on proliferation and differentiation of mouse MC3T3-E1 cells. They also show good osteogenic capability in vivo. So it is a potential bone substitutes for bone defective diseases.
ObjectiveTo investigate the effectiveness of autologous injectable platelet rich fibrin (i-PRF) combined with bone marrow mesenchymal stem cells (BMSCs) for sciatic nerve injury in rats.MethodsBMSCs were isolated and cultured from tibial bone marrow of Sprague Dawley (SD) neonatal rats aged 10-15 days and passaged to the 4th generation. i-PRF was prepared from posterior orbital venous blood of adult SD rats by improved low-speed centrifugation. Twenty-four adult SD rats were selected and randomly divided into 4 groups with 6 rats in each group after the sciatic nerve Ⅲ degree injury model was established by modified crush injury method. Groups A, B, C, and D were injected with BMSCs suspension+autologous i-PRF, autologous i-PRF, BMSCs suspension, and normal saline, respectively. The Basso-Beattie-Bresnahan (BBB) score was used to evaluate the recovery of neurological function of the affected limb of rats every week from 1 to 8 weeks after operation. At 2 months after operation, the rats were sacrificed and the histological changes of sciatic nerve were observed by HE staining. The microstructural changes of nerve fibers, myelin sheath, and nucleus were observed by transmission electron microscope. The expressions of N-cadherin, Nestin, and glial fibrillary acidic protein (GFAP) were detected by Western blot.ResultsNo immune rejection or death occurred in the rats after operation. There was no significant difference in BBB scores between groups at 1 week after operation (P>0.05); at 2-8 weeks after operation, BBB scores in group A were significantly higher than those in groups B, C, and D, and in groups B, C than in group D (P<0.05), there was no significant difference between groups B and C (P>0.05). HE staining showed that the nerve fibers in group A arranged in order, without defect or demyelination; the nerve fibers in group B were not clear and slightly swollen; some of the nerve fibers in group C were disordered and demyelinated; the nerve fibers in group D were not continuous, obviously demyelinated, and some of the nerve adventitia damaged. Transmission electron microscope showed that the structure of nerve fibers in group A was clear, myelin sheath was complete, and nucleus was dense; group B was slightly less than group A; group C had fuzzy structure, demyelination, and hollowing out; group D had disorder structure, demyelination, and hollowing out, and the middle part of nerve adventitia continuity. Western blot detection results showed that there was no significant difference in the relative expression of Nestin between groups (P>0.05). The relative expression of N-cadherin was significantly lower in groups B, C, and D than in group A, in groups C and D than in group B, and in group D than in group C (P<0.05). The relative expression of GFAP was significantly lower in groups B, C, and D than in group A, in group D than in groups B and C (P<0.05); there was no significant difference between groups B and C (P>0.05).ConclusionAutologous i-PRF combined with BMSCs can effectively treat sciatic nerve tissue injury in rats.
ObjectiveTo evaluate the effectiveness of cement-injectable cannulated pedicle screw combined with multiple level Schwab grade Ⅰ osteotomy for chronic thoracolumbar osteoporotic fractures with kyphosis.MethodsThe clinical data of 27 patients with symptomatic chronic thoracolumbar osteoporotic fractures combined with kyphosis treated between June 2015 and June 2017 were retrospectively analysed. Among them, there were 8 males and 19 females, with an average age of 69.5 years (range, 56-81 years). The damage segment (kyphosis vertex) included T11 in 4 cases, T12 in 12 cases, L1 in 10 cases, and L2 in 1 case. The disease duration ranged from 3 to 21 months, with an average of 12.5 months. The T value of lumbar vertebral bone mineral density ranged from −4.9 to −2.5, with an average value of −3.61. The American Spinal Injury Association (ASIA) classification was used to evaluate spinal cord injury, there were 1 case of grade D and 26 cases of grade E. The visual analogue scale (VAS) score, Oswestry disability index (ODI), kyphosis Cobb angle of fracture site, and sagittal vertical axis (SVA) data were obtained before operation, at 2 weeks after operation, 3 months after operation, and last follow-up, to evaluate the quality of life and improvement of sagittal spine parameters.ResultsNo complications related to pedicle screw and bone cement occurred. The incisions healed by first intention in 26 cases, and 1 incision healed after dressing change due to poor blood glucose control. There were no complications such as bedsore, hypostatic pneumonia, or deep venous thrombosis. All patients were followed up 8-24 months, with an average of 16.6 months. The VAS score, ODI score, Cobb angle, and SVA were significantly improved when compared with those before operation (P<0.05). There was no significant difference in Cobb angle between each time point after operation (P>0.05); the VAS score and ODI score at 3 months after operation and last follow-up were significantly better than those at 2 weeks after operation (P<0.05), and the ODI score at last follow-up was further improved when compared with the score at 3 months (P<0.05), but there was no significant difference in VAS score (P>0.05); SVA at last follow-up was significantly worse than that at 2 weeks and 3 months after operation (P<0.05), but there was no significant difference between at 2 weeks and 3 months after operation (P>0.05). During the follow-up period, there was no complication such as pedicle screw loosening, breakage or cutting, adjacent vertebral fracture, proximal junctional kyphosis, and so on.ConclusionFor the chronic thoracolumbar osteoporotic fractures combined with kyphosis, the cement-injectable cannulated pedicle screw and multiple level Schwab grade Ⅰ osteotomy has the advantages of less operation trauma, quick recovery, and remarkable effectiveness.
The aim of this study is to construct an injectable gel with stable phototherapy and chemotherapy. Res-PTX@IR780 gel with phototherapy and chemotherapy property was prepared by introduction of photosensitizer IR780 and antioxidant resveratrol (Res) into the polyethylene glycol (PEG) solution of paclitaxel (PTX). The results showed that PTX, PTX@IR780 and Res-PTX@IR780 could form gels and the gels were injectable. ATR-FTIR results indicated not only components of the gels but also the formation of hydrogen bonding during the gelation. The results of UV showed instability of IR780 solution and stability improvement of Res-IR780 solution under infrared radiation (IR) irradiation. Photothermal tests showed that Res-PTX@IR780 displayed better photothermal conversion and photothermal stability under multiple irradiations than PTX@IR780. The results of in vivo exploration in mice showed that the skin site injected with Res-PTX@IR780 gel heated up from 35 ℃ to 64 ℃, and the temperature difference was up to 30 ℃. Res-PTX@IR780 gel is very promising as a combination agent of photothermal therapy and chemotherapy for the in situ treatment of tumors due to good photothermal conversion and photothermal stability under multiple irradiations.