Biofabrication of reinforced 3D-scaffolds using two-component hydrogels

Abstract

Biofabrication of reinforced 3D-scaff olds using two-component hydrogels Two strategies were developed to 3D print two-component hydrogels by exploiting polymers with thermogelling and chemoselective crosslinking properties. Pre-crosslinking by oxo-ester mediated native chemical ligation of the two components results in well-defi ned 3D printed constructs. Alternatively, mechanical reinforcement of these hydrogels through covalent cross-linking with a functionalized thermoplastic polymer can be achieved by the same chemoselective chemistry. Good cell compatibility was observed for hyaluronic acid containing scaff olds indicating their potential as new materials for biofabrication applications. precursors proceeded after extrusion to form mechanically stable hydrogels that exhibited a storage modulus of 9 kPa after 3 hours. Flow and elastic properties of the polymer solutions and hydrogels were analyzed under similar conditions to those used during the 3D-printing process. These experiments showed the ability to extrude the hydrogels, as well as their rapid recovery after applied shear forces. Hydrogels were printed in grid-like structures, hollow cones and a model representing a femoral condyle, with a porosity of 48 AE 2%. Furthermore, an N-hydroxysuccinimide functionalized thermoplastic poly-e-caprolactone (PCL) derivative was successfully synthesized and 3D-printed. We demonstrated that covalent grafting of the developed hydrogel to the thermoplastic reinforced network resulted in improved mechanical properties and yielded high construct integrity. Reinforced constructs also containing hyaluronic acid showed high cell viability of chondrocytes, underlining their potential for further use in regenerative medicine applications.

Ex vivo model unravelling cell distribution effect in hydrogels for cartilage repair

“…When encapsulating the same number of chondrocytes homogeneously in the hydrogel (condition B), differentiating cell clusters rich in GAGs and collagen type II formed. The formation of such clusters is often observed in cartilage tissue engineering using cell-laden hydrogel constructs, and was also reported for gelMA-based constructs after 2 months of subcutaneous implantation in a rat model (Boere et al, 2015). For a complete mimicry of cartilage architecture, these clusters should mature and reorganize according to the zone in which they are located; however this will depend also on the degradation profile of the hydrogel and its longer-term performance, which could be the subject of future studies.…”

Designing Biomaterials for 3D Printing

“…This reinforced construct exhibited an elastic modulus of 9 kPa after 3 h, and showed high cell viability of chondrocytes. 118 In another study, a photopolymerizable and thermosensitive A-B-A type triblock copolymer ink was developed. 119 The ink was composed of poly( N -(2-hydroxypropyl)methacrylamide lactate) A-blocks partially functionalized with methacrylate groups, and poly(ethylene glycol) B-blocks.…”

Recent advances in hydrogels for cartilage tissue engineering

“…A common composite choice for thermoresponsive “bioinks” consists of HA or chondroitin sulfate mixed with a thermoresponsive polymer. Numerous groups have tested different thermoresponsive materials in this regard, from poly(N-isopropylacrylamide) (pNIPAAM) (Kesti et al ., 2015) to triblock copolymers composed of PEG linked to N-(2-hydroxypropyl) methacrylamide (HPMA) (Boere et al ., 2015). …”