The cell in the ink: Improving biofabrication by printing stem cells for skeletal regenerative medicine

Abstract

Recent advances in regenerative medicine have confirmed the potential to manufacture viable and effective tissue engineering 3D constructs comprising living cells for tissue repair and augmentation. Cell printing has shown promising potential in cell patterning in a number of studies enabling stem cells to be precisely deposited as a blueprint for tissue regeneration guidance. Such manufacturing techniques, however, face a number of challenges including; (i) post-printing cell damage, (ii) proliferation impairment and, (iii) poor or excessive final cell density deposition. The use of hydrogels offers one approach to address these issues given the ability to tune these biomaterials and subsequent application as vectors capable of delivering cell populations and as extrusion pastes. While stem cell-laden hydrogel 3D constructs have been widely established in vitro , clinical relevance, evidenced by in vivo long-term efficacy and clinical application, remains to be demonstrated. This review explores the central features of cell printing, cell-hydrogel properties and cell-biomaterial interactions together with the current advances and challenges in stem cell printing. A key focus is the translational hurdles to clinical application and how in vivo research can reshape and inform cell printing applications for an ageing population.

Nanoclay-based 3D printed scaffolds promote vascular ingrowth ex vivo and generate bone mineral tissue in vitro and in vivo

“…For instance, a hyper-elastic bone (HB) construct printed with a blend made of poly(lactic-co-glycolic acid), polycaprolactone and hydroxyapatite (PLGA/PCL/HAp) has recently shown promising potential for in vivo application [4]. Human bone marrow stromal cells (HBMSCs) have been found to actively participate in bone repair when encapsulated in functional hydrogel networks [5,6] indicating the promise of cell-based strategies to closely recapitulate tissue architecture and functions. As bioprinted tissues promote regeneration in vivo, the tissue should be amenable to remodelling, facilitating the formation of structures driven by cellular and physiological requirements [7].…”

Emulating Human Tissues and Organs: A Bioprinting Perspective Toward Personalized Medicine

“…Adult human stem cells and human pluripotent stem cells (PSCs) are ideal source materials for different targeted biological applications involving 3D bioprinting. Mesenchymal stem cells (MSCs) will not be considered further in this section, and we refer the reader to a very comprehensive review by Cidonio et al 346 Rather, we will focus in this section on PSCs. Human embryonic stem cells (hESC) are stem cells derived directly from the inner cell mass of preimplantation embryo, 347 which in humans comprises less than a dozen cells found at day 5–6 of development.…”

“…The first step has to be to encapsulate PSCs, most commonly in a natural or synthetic hydrogel. 346 , 361 This hydrogel needs to both provide biochemical signals and the right level of physical support. As previously mentioned, natural hydrogels have the advantage that they can consist of decellularized organ-specific ECM components 362 , 363 bearing epitopes which interact with the PSC receptor system (e.g., integrins and their associated transduction machinery) and they generally support PSC maintenance or differentiation.…”

Engineered 3D Polymer and Hydrogel Microenvironments for Cell Culture Applications

“…Similar challenges exist as with extrusion bioprinting apply, namely cell damage during and after printing, stability of the printed structures, and print fidelity and resolution. Recent review of inkjet printing and related bioinks can be found here [55][56][57][58].…”