ABSTRACT
Regenerating the meniscus remains challenging because of its avascular, aneural, and alymphatic nature. Three-dimensional (3D) printing technology provides a promising strategy to fabricate biomimetic meniscal scaffolds with an anisotropic architecture, a proper biomechanical microenvironment, and bioactive components. Herein, 3D printing technology is adopted by coencapsulating chemokines (platelet-derived growth factor-BB, PDGF-BB) and small chondroinductive molecules (kartogenin, KGN) within biomimetic polycaprolactone/hydrogel composite scaffolds. The incorporated PDGF-BB is expected to promote endogenous stem cell homing, and KGN in poly(lactic-co-glycolic) acid microspheres is employed to target the chondrogenesis of resident mesenchymal stem cells (MSCs). First, we chose basic bioinks composed of gelatin methacrylamide and hyaluronic acid methacrylate and then incorporated four concentrations (0%, 0.5%, 1.0%, and 2.0%) of meniscal extracellular matrix into the bioink to systematically study the superiority of these combinations and identify the optimally printable bioink. Next, we investigated the scaffold morphology and drug release profile. The effects of releasing the drugs in a sequentially controlled manner from the composite scaffolds on the fate of MSCs were also evaluated. The biofabricated scaffolds, with and without dual drug loading, were further studied in a rabbit model established with a critical-size medial meniscectomy. We found that meniscal scaffolds containing both drugs had combinational advantages in enhancing cell migration and synergistically promoted MSC chondrogenic differentiation. The dual drug-loaded scaffolds also significantly promotedin vivoneomeniscal regeneration three and six months after implantation in terms of histological and immunological phenotypes. The results presented herein reveal that this 3D-printed dual drug-releasing meniscal scaffold possesses the potential to act as an off-the-shelf product for the clinical treatment of meniscal injury and related joint degenerative diseases.
Subject(s)
Meniscus , Tissue Scaffolds , Animals , Becaplermin/pharmacology , Biomimetics , Printing, Three-Dimensional , Rabbits , Regeneration , Tissue Engineering/methodsABSTRACT
Objective@#To explore the age related increases and characteristics of static stance balance and control strategies of 3-6 years old preschool children,and to provide a reference for the research of children s physique and the practice of physical education.@*Methods@#Using a 2×2×3 (proprioceptive×visual×age) three factor experimental design, standing balance was tested among 105 preschool children aged 3-6 years who were subjected to static for 15 s under four standing postures from January to March 2018. Quantitatively examine the static stance balance ability based on changes in the center of pressure (COP), and quantitatively examine the posture control strategy based on COP frequency domain analysis and nonlinear analysis.@*Results@#Among children aged 3-, 4- and 5-6 years old under the condition of open eyes / hard ground AP_ MV and ML_ MV were 18.05, 16.00, 13.40; 13.55, 11.03, 10.12 mm/s respectively; Under the condition of closed eyes/hard ground, children in three age groupsAP_ MV and ML_ MV were 21.01, 19.60, 15.10; 12.20, 10.20, 10.00 mm/s respectively among three age groups of children. The results showed that the sloshing amplitude and average sloshing velocity decrease significantly with age( P <0.01). Under the conditions of open/hard ground and closed/hard ground, the high frequency band in the left-right direction and the low frequency band in the anterior posterior direction increased significantly with age ( P <0.01). Under the condition of open eyes/hard ground, three age groups of AP_ MF and AP_ HF among three age groups of children were 29.00, 28.61, 27.20； 7.45, 7.44 6.01, respectively, indicating that the middle and high frequency bands ( P <0.01) in the anterior posterior direction decreased significantly with age. ML_FD of children aged 3-, 4- and 5-6 years old under the condition of open eyes / hard ground and closed eyes / hard ground was 1.43, 1.44, 1.52; 1.49, 1.48, 1.56/mm, AP_ FD was 1.58, 1.56, 1.52; 1.56, 1.63, 1.61; AP_MSE was 6.81, 6.90, 5.61 ; 7.25 , 7.41,6.60，respectively. The results show that the fractal dimension in the left right direction increases significantly with age, while the fractal dimension and multi scale entropy in the front back direction decrease significantly( P <0.01).@*Conclusion@#The static stance balance ability of 3-6 years old preschool children shows non linear changes with age,the static posture balance ability of 5-6 years old preschool children is significantly better than that of 3-5 years old , and the balance control strategies of 5-6 years old preschool children is different from that of 3-5 years old.
ABSTRACT
BACKGROUND:Soft tissue engineering mainly includes seed cells,scaffolds,cytokines and bioreactors,among which,the scaffolds are the key link in the construction of tissue-engineered cartilage.OBJECTIVE:To prepare an articular cartilage extracellular matrix/human umbilical cord Wharton gel porous scaffold,and to evaluate its physicochemical properties and biocompatibility.METHODS:The articular cartilage extracellular matrix/human umbilical cord Wharton gel porous scaffold was prepared by freeze thawing drying method using porcine articular cartilage extracellular matrix and human umbilical cord Wharton glue as raw materials.The porosity,water absorption,tissue composition and longitudinal compressive elastic modulus of the scaffold were measured and histologically stained.Rabbit chondrocytes were co-cultured with the articular cartilage extracellular matrix/human umbilical cord Wharton gel porous scaffold for 7 days.Then,scanning electron microscopy,live-dead cell staining and hematoxylin-eosin staining were performed.In addition,rabbit chondrocytes were cultured in the extract of the articular cartilage extracellular matrix/human umbilical cord Wharton gel porous scaffold and cell culture medium for 6 days,respectively;and MTT assay was used to detect cell proliferation.RESULTS AND CONCLUSION:The articular cartilage extracellular matrix/human umbilical cord Wharton gel porous scaffolds had a cross-section of uniform porous network structure and a vertical cross-section of the vertical tubular structure,and the pore wall was densely covered with cartilage fibers.The composite porous scaffold was positive for hematoxylin-eosin staining,safranin O staining and toluidine blue staining,and contained collagen and glycosaminoglycan ingredients.The water absorption,porosity and longitudinal compressive elastic modulus of the scaffolds were (17.418 8±0.909 0)％,(81.495 1±6.621 0)％ and (2.833 3±0.456 4) kPa,respectively.After 7 days of co-culture,rabbit chondrocytes adhered to the scaffold and proliferated,and further grew into the pores of the scaffold.Moreover,the scaffold was non-toxic to the rabbit chondrocytes.To conclude,the physiochemical properties and biochemical components of articular cartilage extracellular matrix/human umbilical cord Wharton gel porous scaffolds are similar to those of natural cartilage,and the scaffold has good biocompatibility.
ABSTRACT
BACKGROUND:Accumulative evidence supports that co-culture technology can be applied to construct the tissue-engineered cartilage with excellent biological characters. OBJECTIVE:To elaborate the co-culture concept and conclude and analyze seed cell sources, cel mixed ratio, spatial y-defined co-culture models and biomaterials in co-culture systems to conclude and analyze the biological characters of tissue-engineered cartilage, and to prospect progression of co-culture systems in cartilage tissue engineering. METHODS:The first author retrieved the databases of PubMed, Web of Science, and CNKI for relative papers published from January 1976 to May 2016 using the keywords ofco-culture, co-culture systems;articular cartilage, chondrocytes, mesenchymal stem cells;tissue engineering, articular cartilage tissue engineeringin English and Chinese, respectively. Finally 60 literatures were included in result analysis, including 1 Chinese and 59 English articles. RESULTS AND CONCLUSION:Co-culture technology emphasizes the role of microenvironment in terms of various physical, chemical and biological factors in the cell processing. In cartilage tissue engineering, co-culture systems contribute to maintain the viability and natural cell phenotype of chondrocytes and induce cartilage differentiation of mesenchymal stem cells. In addition, co-culture technology provides a novel way for cartilage tissue engineering to overcome the shortage of chondrocytes and repair injury to the cartilage-subchondral bone. However, the mechanisms of cell-cell interaction in co-culture systems still need to be explored in depth, so as to optimize the co-culturing conditions and construct perfect tissue-engineered cartilage.
