Various hydrogels derived from the xenogeneic extracellular matrix (ECM) have been utilised to promote the repair and reconstruction of numerous tissues; however, there are few studies on hydrogels derived from allogeneic specimens. Human placenta derived hydrogels have been used in the therapy of ischaemic myocardium; however, their physicochemical properties and effects on cellular behaviour remain elusive. As the human placenta retains pro-angiogenic growth factors, it is hypothesized that the placenta hydrogels possess the potential to improve angiogenesis. In this study, a soluble decellularized human placenta matrix generated using a modified method could be stored in a powder form and could be used to form a hydrogel in vitro. Effective decellularization was evaluated by analysing the DNA content and histology images. The placenta hydrogel exhibited a fibrous porous morphology and was injectable. Fourier transform infrared (FTIR) spectroscopy revealed that the placenta hydrogel contained both collagen and sulfated glycosaminoglycans (GAGs). In addition, immunofluorescence imaging and enzyme-linked immunosorbent assay (ELISA) showed that the placenta hydrogel retained pro-angiogenic growth factors, including VEGF and bFGF, and transforming growth factor-β1 (TGF-β1). Further in vitro and in vivo analyses confirmed that the placenta hydrogel exerted better pro-angiogenic effects than a collagen type I hydrogel. Histological data also showed that the placenta hydrogels did not elicit a grave inflammatory response. In conclusion, the results suggest that placenta hydrogels may be deemed an attractive scaffold for regenerative medicine applications, especially in promoting vessel formation.
To reconstruct and restore the functions of the male urethra is a challenging task for urologists. The acellular matrix graft currently used in the clinics is mono-functional and may cause a series of complications including stricture, fibrosis, and stone formation. As a result, such graft materials cannot meet the increasing demand for multifunctionality in the field of urethral tissue engineering. In this context, a multifunctional urethral patch is designed for the repair of urethral defects by mixing protocatechualdehyde (PCA) with small intestinal submucosa (SIS) under an alkalin condition to allow cross linking. As shown, the PCA/SIS patch possesses excellent biocompatibility, antioxidant activity, and anti-inflammatory property. More importantly, this patch can remarkably promote the adhesion, proliferation, and directional extension of rabbit bladder epithelial mucous cells (R-EMCs) as well as rabbit bladder smooth muscle cells (R-SMCs), and upregulate the expression of cytokeratin in the EMCs and contractile protein in the SMCs in vitro. In vivo experiments also confirm that the PCA/SIS patch can significantly enhance scarless repair of urethral defects in rabbits by facilitating smooth muscle regeneration, reducing excessive collagen deposition, and accelerating re-epithelialization and neovascularization. Taken together, the newly developed multifunctional PCA/SIS patch provides a promising candidate for urethral regeneration.
To prepare the small intestinal submucosa (SIS)-silk composite scaffold for anterior cruciate ligament (ACL) reconstruction, and to evaluate its properties of biomechanics, biocompatibility, and the influence on synovial fluid leaking into tibia tunnel so as to provide a better choice in the clinical application of ACL reconstruction.The silk was used to remove sericin and then weaved as silk scaffold, which was surrounded cylindrically by SIS to prepare a composite scaffold. The property of biomechanics was evaluated by biomechanical testing system. The cell biocompatibility of scaffolds was evaluated by live/dead staining and the cell counting kit 8 (CCK- 8). Thirty 6-week-old Sprague Dawley rats were randomly assigned to 2 groups (n = 15). The silk scaffold (S group) and composite scaffold (SS group) were subcutaneously implanted. At 2, 4, and 8 weeks after implanted, the specimen were harvested for HE staining to observe the biocompatibility. Another 20 28-week-old New Zealand white rabbits were randomly assigned to the S group and SS group (n = 20), and the silk scaffold and composite scaffold were used for ACL reconstruction respectively in 2 groups. Furthermore, a bone window was made on the tibia tunnel. At last, the electric resistance of tendon graft in the bone window was measured and recorded at different time points after 5 mL of 10% NaCl or 5 mL of ink solution was irrigated into the joint cavity recspectively.The gross observation showed that the composite scaffold consisted of the helical silk bundle inside which was surrounded by SIS. The maximal load of silk scaffold and composite scaffold was respectively (138.62 ± 11.41) N and (137.05± 16.95) N, showing no significant difference (P > 0.05); the stiffness was respectively (24.65 ± 2.62) N/mm and (24.21 ± 2.39) N/mm, showing no significant difference (P > 0.05). The live/dead staining showed that the cells had good activity on both scaffolds. However, the cells on the composite scaffold had better extensibility. In addition, the cell proliferation curve indicated that no significant difference in the absorbance (A) values was founded between groups at various time points (P > 0.05). HE staining showed less inflammatory cells and much more angiogenesis in SS group than in S group at 2, 4, and 8 weeks after subcutaneously implanted (P < 0.05), indicating good biocompatibility. Additionally, the starting time points of electric resistance decrease and the ink leakage were both significantly later in SS group than in S group (P < 0.05). The duration of ink leakage was significantly longer in SS group than in S group (P < 0.05).The SIS-silk composite scaffold has excellent biomechanical properties and biocompatibility and early vacularization after in viva implantation. Moreover, it can reducing the leakage of synovial fluid into tibia tunnel at the early stage of ACE reconstruction. So it is promising to be an ideal ACL scaffold.
Endoscopic submucosal dissection (ESD) for gastrointestinal tumors and premalignant lesions needs submucosal fluid cushion (SFC) for mucosal uplift before dissection, and wound care including wound closure and rapid healing postoperatively. Current SFC materials as well as materials and/or methods for post-ESD wound care have single treatment effect and hold corresponding drawbacks, such as easy dispersion, short duration, weak hemostasis and insufficient repair function. Thus, designing materials that can serve as both SFC materials and wound care is highly desired, and remains a challenge. Herein, we report a two-component in-situ hydrogel prepared from maleimide-based oxidized sodium alginate and sulfhydryl carboxymethyl-chitosan, which gelated mainly based on "click" chemistry and Schiff base reaction. The hydrogels showed short gelation time, outstanding tissue adhesion, favorable hemostatic properties, and good biocompatibility. A rat subcutaneous ultrasound model confirmed the ability of suitable mucosal uplift height and durable maintenance time of AM solution. The in vivo/in vitro rabbit liver hemorrhage model demonstrated the effects of hydrogel in rapid hemostasis and prevention of delayed bleeding. The canine esophageal ESD model corroborated that the in-situ hydrogel provided good mucosal uplift and wound closure effects, and significantly accelerated wound healing with accelerating re-epithelization and ECM remodeling post-ESD. The two-component in-situ hydrogels exhibited great potential in gastrointestinal tract ESD.
Background: Osteoarthritis (OA) is a common disease that causes joint pain and disability. Stem cell therapy is emerging as a promising treatment for OA. Purpose: To evaluate the ability of peripheral blood–derived mesenchymal stem cells (PBMSCs) combined with donor-matched platelet-rich plasma (PRP) to treat OA in a rabbit model. Study Design: Controlled laboratory study. Methods: PBMSCs and donor-matched PRP were isolated and prepared from the same rabbit. PBMSCs were treated with serum-free medium, fetal bovine serum, and PRP; a series of PBMSC behaviors, including proliferation, migration, and adhesion, were compared among groups. The ability of PBMSCs or PRP alone and PBMSCs+PRP to protect chondrocytes against proinflammatory cytokine (interleukin 1β [IL-1β]) treatment was compared by analyzing reactive oxygen species (ROS)–scavenging ability and apoptosis. Real-time quantitative polymerase chain reaction and immunofluorescence were used to investigate the expression of extracellular matrix (ECM) metabolism genes and proteins, and Western blotting was used to explore the potential mechanism of the corresponding signaling pathway. In vivo, the effect of PBMSCs+PRP on cartilage and inflammation of the synovium was observed in a surgery-induced OA rabbit model via gross observation, histological and immunohistochemical staining, and enzyme-linked immunosorbent assay. Results: Proliferation, migration, and adhesion ability were enhanced in PBMSCs treated with PRP. Moreover, compared with either PBMSCs or PRP alone, PBMSCs+PRP enhanced ROS-scavenging ability and inhibited apoptosis in IL-1β–treated chondrocytes. PBMSCs+PRP also reversed the IL-1β–induced degradation of collagen type 2 and aggrecan and increased expression of matrix metalloproteinase 13, and this effect was related to increased expression of ECM synthesis and decreased expression of degradation and inflammatory genes and proteins. Mechanistically, PBMSCs+PRP reduced the phosphorylation of inhibitor of nuclear factor-κBα (IκBα), which further inhibited the phosphorylation of downstream nuclear factor–κB (NF-κB) in the NF-κB signaling pathway. In vivo, compared with PBMSCs or PRP alone, intra-articular (IA) injection of PBMSCs+PRP enhanced cartilage regeneration and attenuated synovial inflammation in OA-induced rabbits. Conclusion: These results demonstrate that PRP could enhance biological activities, including viability, migration, and adhesion, in PBMSCs. PBMSCs+PRP could rescue ECM degeneration by inhibiting inflammatory signaling in IL-1β–treated OA chondrocytes. In addition, IA injection of PBMSCs+PRP effectively attenuated OA progression in a surgery-induced OA rabbit model. Clinical Relevance: PBMSCs+PRP may provide a promising treatment for knee OA, and this study can advance the related basic research.
Abstract Lipofilling is a popular technique for soft tissue augmentation, limited by unpredictable graft survival. This study aimed at exploring the effect of hydrogel from acellular porcine adipose tissue (HAPA) on angiogenesis and survival of adipose tissue used for lipofilling. The effect of HAPA on adipose-derived stem cells (ADSCs) proliferation, adipogenic differentiation, and vascular endothelial growth factor (VEGF) secretion were evaluated in hypoxia and normoxia in vitro . For the in vivo study, adipose tissue with phosphate buffered saline, ADSCs, and HAPA (with or without ADSCs) were co-injected subcutaneously into nude mice. HAPA–ADSCs mixture (tissue engineering adipose tissue) was also grafted. Gross observation, volume measurement, and ultrasound observation were assessed. For histological assessment, hematoxylin and eosin, perilipin, cluster of differentiation 31 (CD31), Ki67, and transferase-mediated d-UTP nick end labelling (TUNEL) staining were performed. HAPA improved ADSCs proliferation, VEGF secretion, and adipogenic differentiation under normoxia and hypoxia conditions in vitro study. For the in vivo study, HAPA showed improved volume retention and angiogenesis, and reduced cell apoptosis when compared to ADSCs-assisted lipofilling and pure lipofilling. In conclusion, HAPA could maintain ADSCs viability and improve cell resistant to hypoxia and might be a promising biomaterial to assist lipofilling.
To evaluate the effectiveness of open reduction and internal fixation (ORIF) in treatment of acute and delayed occult Lisfranc injuries.A retrospective review of 26 patients with occult Lisfranc injuries who were treated with ORIF between July 2010 and July 2015 was applied. Fourteen patients were treated within 6 weeks after injury (acute group) and 12 patients were treated after 6 weeks of injury (delayed group). There was no significant difference between the two groups in gender, age, affected sides, and preoperative visual analogue scale (VAS) score, American Orthopedic Foot and Ankle Society (AOFAS) score, and physical and mental scores of Study Short Form 12 Health Survey (SF-12) ( P<0.05). The joint reduction, internal fixator, and traumatic osteoarthritis were observed by X-ray films. The pain degree, midfoot function, and quality of life were evaluated with VAS score, AOFAS score, and physical and mental scores of SF-12.All incisions healed by first intention with no complications. All patients were followed up with the mean follow-up time of 15 months (range, 12-24 months) in acute group and 15 months (range, 12-23 months) in delayed group. At last follow-up, the VAS score, AOFAS score, and physical and mental scores of SF-12 were superior to those before operation in the two groups ( P<0.05). And there was no significant difference in all indicators between the two groups ( P>0.05). The satisfaction rates were 100% and 83.3% (10/12) in acute group and delayed group, respectively. The internal fixators were removed in 20 patients (11 cases in acute group and 9 cases in delayed group) at 9-24 months after operation (mean, 14.5 months). The results of X-ray films showed no traumatic osteoarthritis, midfoot collapse, internal fixation failure, or reduction loss during follow-up period.ORIF is an ideal method for both acute and delayed occult Lisfranc injuries and can obtain the similar effectiveness.比较切开复位内固定（open reduction and internal fixation，ORIF）治疗新鲜与陈旧隐性 Lisfranc 损伤的疗效。.回顾分析 2010 年 7 月—2015 年 7 月采用 ORIF 治疗且符合选择标准的隐性 Lisfranc 损伤患者临床资料，其中 14 例于伤后 6 周内手术（新鲜组），12 例于 6 周后手术（陈旧组）。两组患者性别、年龄、损伤侧别以及术前疼痛视觉模拟评分（VAS）、美国矫形足踝协会（AOFAS）评分、简明生活质量量表（SF-12 量表）心理及生理评分比较，差异均无统计学意义（ P>0.05）。术后摄 X 线片，观察 Lisfranc 关节复位、内固定物在位情况以及有无创伤后关节炎等并发症发生。采用 VAS 评分评价关节疼痛程度，AOFAS 评分评价中足功能，SF-12 量表心理及生理评分评价患者生活质量。.术后两组切口均Ⅰ期愈合，无相关并发症发生。两组患者均获随访，其中新鲜组随访时间 12～24 个月，平均 15 个月；陈旧组随访时间 12～23 个月，平均 15 个月。末次随访时，两组 VAS 评分、AOFAS 评分、SF-12 量表生理及心理评分均优于术前（ P<0.05）；组间比较差异均无统计学意义（ P>0.05）。新鲜组患者手术疗效满意率 100%，陈旧组为 83.3%（10/12）。术后 9～24 个月 20 例患者（新鲜组 11 例、陈旧组 9 例）二次手术取出内固定物，平均取出时间为 14.5 个月。X 线片复查示随访期间未见关节炎表现及中足塌陷，无内固定失效及复位丢失。.ORIF 治疗新鲜和陈旧隐性 Lisfranc 损伤可获得相似疗效。.
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