Lipid Mictrotubes as a Nutrient Reservoir or Enzyme Delivery Vehicle in Engineered Cartilage

Author(s):  
Grace D. O’Connell ◽  
Clare Gollnick ◽  
Gerard A. Ateshian ◽  
Ravi V. Bellamkonda ◽  
Clark T. Hung

Tissue-engineered cartilage using a hydrogel scaffold is capable of achieving native compressive properties and glycosaminglycan (GAG) content [1]. However, these tissues are limited in their collagen production and closer inspection of the localized mechanical properties demonstrates that mature constructs consist of a stiffer periphery region surrounding a softer core [1, 2]. Nutrient diffusion becomes increasingly more challenging as the cells in the construct periphery deposit extracellular matrix. Altering the scaffold porosity by adding microscopic porogens can improve the nutrient diffusion into the center of the construct [3]. Furthermore, chondroitinase ABC (chABC) has been shown to improve collagen production of mature engineered cartilage (i.e. tissue cultured for 2–4 weeks before chABC digestion). Lipid microtubes, designed to slowly release chABC for spinal chord injury repair can be incorporated into our agarose hydrogel scaffold in a chABC-loaded or unloaded form. The objective of this study was to explore the use of lipid microtubes in our scaffold as a tubular porogen and as a vehicle to deliver chABC throughout the scaffold to improve nutrient diffusion and collagen production into our engineered constructs.

Author(s):  
Grace D. O’Connell ◽  
Clare Gollnick ◽  
Gerard A. Ateshian ◽  
Ravi V. Bellamkonda ◽  
Clark T. Hung

Tissue-engineered cartilage using a hydrogel scaffold is capable of achieving native compressive properties and glycosaminglycan (GAG) content [1]; however, promoting collagen growth towards native values has been challenging. As the cells in the cartilage constructs deposit matrix over time in culture, transport of nutrients to the construct center becomes increasingly hindered [2]. Digestion of mature tissue engineered constructs with chondroitinase (chABC) temporarily suppresses the GAG content, allowing an increase in the collagen content and eventually improving the mechanical properties after GAG content recovers [1]. However, adding chABC into the feeding media limits its effectiveness to the construct’s periphery, reflecting enzyme diffusion gradients. Additionally, long-term use of chABC, without re-application, is limited since its enzymatic activity degrades within 5 days at 37°C [3]. Lee and co-workers have developed a method for delivering thermostabilized chABC using sugar trehalose and hydrogel-microtubes for applications desiring extended enzyme release [4]. Lipid microtubes loaded with thermostabilized chABC may be incorporated into an agarose hydrogel scaffold to provide long-term release of the enzyme uniformly throughout the construct [3]. The objective of this study was to test the hypothesis that chABC-filled microtubes will enhance in vitro development of engineered cartilage.


RSC Advances ◽  
2015 ◽  
Vol 5 (98) ◽  
pp. 80688-80697 ◽  
Author(s):  
Changjiang Fan ◽  
Dong-An Wang

A chondroitin sulfate (CS)–alginate bead composite gel (CS–ABG) is developed, and which exhibits superiority to aid cartilage regeneration.


Author(s):  
Liming Bian ◽  
Kenneth W. Ng ◽  
Eric G. Lima ◽  
Gerard A. Ateshian ◽  
Clark T. Hung

It has been shown that chondrocyte-seeded agarose constructs of large dimensions develop spatially inhomogeneous material properties with stiffer outer edges and a softer central core [1]. This axial (depth-dependent) inhomogeneity was observed for constructs with relatively large diameter (4mm) and thickness (2.3mm) and suggests nutrient diffusion limitations to the central region of the constructs. Our previous study also showed that by reducing the thickness of the agarose construct (to 1mm) more homogenous construct properties can be obtained as a result of the reduced diffusion distance [2]. In this study we hypothesized that more homogeneous constructs of better mechanical properties could be achieved by creating channels running through the depth of the thick constructs (2.3mm), thereby facilitating nutrient diffusion into the central region of the constructs.


2021 ◽  
Author(s):  
Alexandre DUFOUR ◽  
Xavier Barceló Gallostra ◽  
Conor OKeeffe ◽  
Kian F Eichholz ◽  
Stanislas Von Euw ◽  
...  

Successful cartilage engineering requires the generation of biological grafts mimicking the structure, composition and mechanical behaviour of the native tissue. Here melt-electrowriting (MEW) was used to produce arrays of polymeric structures whose function was to orient the growth of cellular aggregates spontaneously generated within these structures, and to provide tensile reinforcement to the resulting tissues. Inkjeting was used to deposit defined numbers of cells into MEW structures, which self-assembled into an organized array of spheroids within hours, ultimately generating a hybrid tissue that was hyaline-like in composition. Structurally, the engineered cartilage mimicked the histotypical organization observed in skeletally immature synovial joints. This biofabrication framework was then used to generate scaled-up (50mm x 50mm) cartilage implants containing over 3,500 cellular aggregates in under 15 minutes. After 8 weeks in culture, a 50-fold increase in the compressive properties of these MEW reinforced tissues were observed, while the tensile properties were still dominated by the polymer network, resulting in a composite construct demonstrating tension-compression nonlinearity mimetic of the native tissue. Helium ion microscopy further demonstrated the development of an arcading collagen network within the engineered tissue. This hybrid bioprinting strategy provides a versatile and scalable approach to engineer cartilage biomimetic grafts for biological joint resurfacing.


2013 ◽  
Vol 51 (01) ◽  
Author(s):  
S Jörs ◽  
P Jeliazkova ◽  
M Ringelhan ◽  
J Ferrer ◽  
RM Schmid ◽  
...  
Keyword(s):  

2019 ◽  
Vol 26 (4) ◽  
pp. 197-208
Author(s):  
Leo Gu Li ◽  
Albert Kwok Hung Kwan

Previous research studies have indicated that using fibres to improve crack resistance and applying expansive agent (EA) to compensate shrinkage are both effective methods to mitigate shrinkage cracking of concrete, and the additions of both fibres and EA can enhance the other performance attributes of concrete. In this study, an EA was added to fibre reinforced concrete (FRC) to produce concrete mixes with various water/binder (W/B) ratios, steel fibre (SF) contents and EA contents for testing of their workability and compressive properties. The test results showed that adding EA would slightly increase the superplasticiser (SP) demand and decrease the compressive strength, Young’s modulus and Poisson’s ratio, but significantly improve the toughness and specific toughness of the steel FRC produced. Such improvement in toughness may be attributed to the pre-stress of the concrete matrix and the confinement effect of the SFs due to the expansion of the concrete and the restraint of the SFs against such expansion.


Sign in / Sign up

Export Citation Format

Share Document