3D bioactive composite scaffolds for bone tissue engineering.

Tissue engineering has become a promising strategy for repairing damaged cartilage and bone tissue Among the scaffolds for tissue-engineering applications, injectable hydrogels have demonstrated great potential for use as three-dimensional cell culture scaffolds in cartilage and bone tissue engineering, owing to their high water content, similarity to the natural extracellular matrix (ECM), porous framework for cell transplantation and proliferation, minimal invasive properties, and ability to match irregular defects In this review, we describe the selection of appropriate biomaterials and fabrication methods to prepare novel injectable hydrogels for cartilage and bone tissue engineering In addition, the biology of cartilage and the bony ECM is also summarized Finally, future perspectives for injectable hydrogels in cartilage and bone tissue engineering are discussed

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Injectable hydrogels for cartilage and bone tissue engineering.

Bioprinting is a process based on additive manufacturing from materials containing living cells. These materials, often referred to as bioink, are based on cytocompatible hydrogel precursor formulations, which gel in a manner compatible with different bioprinting approaches. The bioink properties before, during and after gelation are essential for its printability, comprising such features as achievable structural resolution, shape fidelity and cell survival. However, it is the final properties of the matured bioprinted tissue construct that are crucial for the end application. During tissue formation these properties are influenced by the amount of cells present in the construct, their proliferation, migration and interaction with the material. A calibrated computational framework is able to predict the tissue development and maturation and to optimize the bioprinting input parameters such as the starting material, the initial cell loading and the construct geometry. In this contribution relevant bioink properties are reviewed and discussed on the example of most popular bioprinting approaches. The effect of cells on hydrogel processing and vice versa is highlighted. Furthermore, numerical approaches were reviewed and implemented for depicting the cellular mechanics within the hydrogel as well as for prediction of mechanical properties to achieve the desired hydrogel construct considering cell density, distribution and material-cell interaction.

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Bioink properties before, during and after 3D bioprinting

Given their durability and long-term stability, self-healable hydrogels have, in the past few years, emerged as promising replacements for the many brittle hydrogels currently being used in preclinical or clinical trials. To this end, the incompatibility between hydrogel toughness and rapid self-healing remains unaddressed, and therefore most of the self-healable hydrogels still face serious challenges within the dynamic and mechanically demanding environment of human organs/tissues. Furthermore, depending on the target tissue, the self-healing hydrogels must comply with a wide range of properties including electrical, biological, and mechanical. Notably, the incorporation of nanomaterials into double-network hydrogels is showing great promise as a feasible way to generate self-healable hydrogels with the above-mentioned attributes. Here, the recent progress in the development of multifunctional and self-healable hydrogels for various tissue engineering applications is discussed in detail. Their potential applications within the rapidly expanding areas of bioelectronic hydrogels, cyborganics, and soft robotics are further highlighted.

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Self-Healing Hydrogels: The Next Paradigm Shift in Tissue Engineering?

Tissue engineering has emerged as a new treatment approach for bone repair and regeneration seeking to address limitations associated with current therapies, such as autologous bone grafting. While many bone tissue engineering approaches have traditionally focused on synthetic materials (such as polymers or hydrogels), there has been a lot of excitement surrounding the use of natural materials due to their biologically inspired properties. Fibrin is a natural scaffold formed following tissue injury that initiates hemostasis and provides the initial matrix useful for cell adhesion, migration, proliferation, and differentiation. Fibrin has captured the interest of bone tissue engineers due to its excellent biocompatibility, controllable biodegradability, and ability to deliver cells and biomolecules. Fibrin is particularly appealing because its precursors, fibrinogen, and thrombin, which can be derived from the patient's own blood, enable the fabrication of completely autologous scaffolds. In this article, we highlight the unique properties of fibrin as a scaffolding material to treat bone defects. Moreover, we emphasize its role in bone tissue engineering nanocomposites where approaches further emulate the natural nanostructured features of bone when using fibrin and other nanomaterials. We also review the preparation methods of fibrin glue and then discuss a wide range of fibrin applications in bone tissue engineering. These include the delivery of cells and/or biomolecules to a defect site, distributing cells, and/or growth factors throughout other pre-formed scaffolds and enhancing the physical as well as biological properties of other biomaterials. Thoughts on the future direction of fibrin research for bone tissue engineering are also presented. In the future, the development of fibrin precursors as recombinant proteins will solve problems associated with using multiple or single-donor fibrin glue, and the combination of nanomaterials that allow for the incorporation of biomolecules with fibrin will significantly improve the efficacy of fibrin for numerous bone tissue engineering applications.

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A review of fibrin and fibrin composites for bone tissue engineering

An overview of injectable polymeric hydrogels for tissue engineering

Erratum : An Overview of Injectable Polymeric Hydrogels for Tissue Engineering

Injectable hydrogels with their 3D structure and good moldability serve as excellent scaffolding material for regenerating irregular non load-bearing bone defects. Most of the bone defects do not heal completely due to the lack of vasculature required for the transport of nutrients and oxygen to the regenerating tissues. To enhance vasculature, we developed an injectable hydrogel system made of chitin and poly (butylene succinate) (PBSu) loaded with 250  ±  20 nm sized fibrin nanoparticles (FNPs) and magnesium-doped bioglass (MBG). FNPs were expected to enhance vascularisation and MBG was expected to help induce early osteogenesis. Composite hydrogels were analysed using Fourier transform infra-red spectroscopy, scanning electron microscopy (SEM), energy dispersive x-ray spectroscopy, and rheology. Hydrogels with MBG showed a slightly rougher morphology upon SEM analysis. Composites containing 5% MBG and 2% FNPs showed good rheological properties, injectability, temperature stability, biomineralization and protein adsorption. Human umbilical vein endothelial cells (HUVECs) and rabbit-adipose derived mesenchymal stem cells (rASCs) were used for cyto-compatibility studies. Composite gels with 2% FNPs and 2% MBG (composite 1) were considered to be non-toxic to both the cells and were taken for further in vitro studies. Aortic ring assay was carried out to study the angiogenic potential of the hydrogels. The aorta placed with composite hydrogels showed enhanced sprouting of blood vessels. rASCs too showed good spreading on the composite hydrogels. Hydrogels containing MBG showed early initiation of differentiation and higher expression of alkaline phosphatase and osteocalcin confirming the osteoinductive property of MBG. These studies indicate that this composite hydrogel can be used for regenerating irregular bone defects.

https://iopscience.iop.org/article/10.1088/1748-6041/11/3/035017/pdf

M. Vishnu Priya

Papers

An overview of injectable polymeric hydrogels for tissue engineering

Erratum : An Overview of Injectable Polymeric Hydrogels for Tissue Engineering

Injectable osteogenic and angiogenic nanocomposite hydrogels for irregular bone defects.

Colloidal chitin nanogels: A plethora of applications under one shell

Erratum to “An overview of injectable polymeric hydrogels for tissue engineering” [Eur. Polym. J. 72 (2015) 543–565]