In situhandheld three‐dimensional bioprinting for cartilage regeneration

Abstract

Articular cartilage injuries experienced at an early age can lead to the development of osteoarthritis later in life. In situ three-dimensional (3D) printing is an exciting and innovative biofabrication technology that enables the surgeon to deliver tissue-engineering techniques at the time and location of need. We have created a hand-held 3D printing device (biopen) that allows the simultaneous coaxial extrusion of bioscaffold and cultured cells directly into the cartilage defect in vivo in a single-session surgery. This pilot study assessed the ability of the biopen to repair a full-thickness chondral defect and the early outcomes in cartilage regeneration, and compared these results with other treatments in a large animal model. A standardized critical-sized full-thickness chondral defect was created in the weight-bearing surface of the lateral and medial condyles of both femurs of six sheep. Each defect was treated with one of the following treatments: (i) hand-held in situ 3D printed bioscaffold using the biopen (HH group), (ii) preconstructed bench-based printed bioscaffolds (BB group), (iii) microfractures (MF group) or (iv) untreated (control, C group). At 8 weeks after surgery, macroscopic, microscopic and biomechanical tests were performed. Surgical 3D bioprinting was performed in all animals without any intra- or postoperative complication. The HH biopen allowed early cartilage regeneration. The results of this study show that real-time, in vivo bioprinting with cells and scaffold is a feasible means of delivering a regenerative medicine strategy in a large animal model to regenerate articular cartilage.

3D Bioprinting: from Benches to Translational Applications

“…A different strategy for in situ bioprinting, which has already shown promising translation to the clinics, is the use of handheld bioprinting devices . Di Bella et al developed a handheld 3D bioprinting pen (biopen) for the treatment of articular cartilage damage ( Figure A) . The biopen was designed to simultaneously extrude a bioscaffold consisting of GelMA‐MeHA and MSCs directly into a cartilage defect.…”

“…B) Treatment of a full‐thickness chondral defect made in the weight bearing area of the medial and lateral femoral condyles using the biopen. A,B) Reproduced with permission . Copyright 2017, John Wiley & Sons, Ltd. C) Schematic of a handheld skin bioprinter displaying (top left) working principle, (top right) a rendered image of the handheld bioprinter, (bottom left) photograph of the bioink cartridge combining different bioinks, and (bottom right) schematic of the application process of planar skin sheets.…”

In situ Enabling Approaches for Tissue Regeneration: Current Challenges and New Developments

“…Building human tissues by 3D bioprinting has received huge attention in the TE field due to its process flexibility and versatility. However, the need to implant the structure after production has generated several issues related to the integration with surrounding tissues, namely, (i) the difficulties to obtain a perfect fit for the geometry of the defect, (ii) the need for surgical debridement before scaffold implantation, and (iii) the contamination risk (Akilbekova and Mektepbayeva, 2017;Bella et al, 2018). To overcome these limitations, in situ bioprinting emerged to directly print biostructures into the patient's affected tissue.…”

“…Therefore, in situ approaches need stateof-the-art customized processing technologies. The advances in micro-and nano-fabrication technologies can provide the platforms to engineer structures at high resolution with the capacity to fully recreate in situ the complexity of a tissue defect (Holzmond and Li, 2017;Bella et al, 2018;Hakimi et al, 2018;Hudita et al, 2019).…”

Hyaline cartilage next generation implants from adipose-tissue-derived mesenchymal stem cells: Comparative study on 3D-printed polycaprolactone scaffold patterns

“…Bioprinting can control cell distribution and modulate the mechanical and chemical properties of the cartilaginous construct. Recent development in the field is the use of a “biopen” that can inject the bioscaffold and cultured cells directly into the cartilage defect in vivo in a single‐session surgery (Di Bella et al, ; Roseti et al, ). Till today, full reconstruction of large cartilage defects has not yet been accomplished, and most importantly, the mechanical properties of the native cartilage needed to withstand the loadings of daily human activities cannot be reproduced (Armiento, Stoddart, Alini, & Eglin, ; Li, Xiao, Li, & Zhu, ; Versier, Dubrana, & French Arthroscopy, ).…”