Bone tissue engineering (BTE) is a rapidly growing field aiming to create a biofunctional tissue that can integrate and degrade in vivo to treat diseased or damaged tissue. It has become evident that scaffold fabrication techniques are very important in dictating the final structural, mechanical properties, and biological response of the implanted biomaterials. A comprehensive review of the current accomplishments on scaffold fabrication techniques, their structure, and function properties for BTE is provided herein. Different types of biomaterials ranging from inorganic biomaterials to natural and synthetic polymers and related composites for scaffold processing are presented. Emergent scaffolding techniques such as electrospinning, freeze-drying, bioprinting, and decellularization are also discussed. Strategies to improve vascularization potential and immunomodulation, which is considered a grand challenge in BTE scaffolding, are also presented.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/adfm.202010609

Scaffold fabrication technologies and structure/function properties in bone tissue engineering

The extracellular matrix (ECM) is a complex network with multiple functions, including specific functions during tissue regeneration. Precisely, the properties of the ECM have been thoroughly used in tissue engineering and regenerative medicine research, aiming to restore the function of damaged or dysfunctional tissues. Tissue decellularization is gaining momentum as a technique to obtain potentially implantable decellularized extracellular matrix (dECM) with well-preserved key components. Interestingly, the tissue-specific dECM is becoming a feasible option to carry out regenerative medicine research, with multiple advantages compared to other approaches. This review provides an overview of the most common methods used to obtain the dECM and summarizes the strategies adopted to decellularize specific tissues, aiming to provide a helpful guide for future research development.

https://www.mdpi.com/1422-0067/21/15/5447/pdf

Tissue-Specific Decellularization Methods: Rationale and Strategies to Achieve Regenerative Compounds.

An overview of extrusion-based bioprinting with a focus on induced shear stress and its effect on cell viability

Biomaterials have had an increasingly important role in recent decades, in biomedical device design and the development of tissue engineering solutions for cell delivery, drug delivery, device integration, tissue replacement, and more. There is an increasing trend in tissue engineering to use natural substrates, such as macromolecules native to plants and animals to improve the biocompatibility and biodegradability of delivered materials. At the same time, these materials have favourable mechanical properties and often considered to be biologically inert. More importantly, these macromolecules possess innate functions and properties due to their unique chemical composition and structure, which increase their bioactivity and therapeutic potential in a wide range of applications. While much focus has been on integrating these materials into these devices via a spectrum of cross-linking mechanisms, little attention is drawn to residual bioactivity that is often hampered during isolation, purification, and production processes. Herein, we discuss methods of initial material characterisation to determine innate bioactivity, means of material processing including cross-linking, decellularisation, and purification techniques and finally, a biological assessment of retained bioactivity of a final product. This review aims to address considerations for biomaterials design from natural polymers, through the optimisation and preservation of bioactive components that maximise the inherent bioactive potency of the substrate to promote tissue regeneration.

/pdf/bioactive-potential-of-natural-biomaterials-identification-2dcv1q15m7.pdf

Bioactive potential of natural biomaterials: identification, retention and assessment of biological properties.

Biologic scaffold materials composed of allogeneic or xenogeneic extracellular matrix (ECM) are commonly used for the repair and remodeling of injured tissue. The clinical outcomes associated with implantation of ECM-based materials range from unacceptable to excellent. The variable clinical results are largely due to differences in the preparation of the material, including characteristics of the source tissue, the method and efficacy of decellularization, and post-decellularization processing steps. The mechanisms by which ECM scaffolds promote constructive tissue remodeling include mechanical support, degradation and release of bioactive molecules, recruitment and differentiation of endogenous stem/progenitor cells, and modulation of the immune response toward an anti-inflammatory phenotype. The methods of ECM preparation and the impact of these methods on the quality of the final product are described herein. Examples of favorable cellular responses of immune and stem cells associated with constructive tissue remodeling of ECM bioscaffolds are described.

Extracellular Matrix-Based Biomaterials and Their Influence Upon Cell Behavior.

As the gap between donors and patients in need of an organ transplant continues to widen, research in regenerative medicine seeks to provide alternative strategies for treatment. One of the most promising techniques for tissue and organ regeneration is decellularization, in which the extracellular matrix (ECM) is isolated from its native cells and genetic material in order to produce a natural scaffold. The ECM, which ideally retains its inherent structural, biochemical, and biomechanical cues, can then be recellularized to produce a functional tissue or organ. While decellularization can be accomplished using chemical and enzymatic, physical, or combinative methods, each strategy has both benefits and drawbacks. The focus of this review is to compare the advantages and disadvantages of these methods in terms of their ability to retain desired ECM characteristics for particular tissues and organs. Additionally, a few applications of constructs engineered using decellularized cell sheets, tissues, and whole organs are discussed.

/pdf/decellularization-strategies-for-regenerative-medicine-from-1uy9bujc6h.pdf

Decellularization Strategies for Regenerative Medicine: From Processing Techniques to Applications

The gas exchange units of the lung, the alveoli, are mechanically active and undergo cyclic deformation during breathing. The epithelial cells that line the alveoli contribute to lung function by reducing surface tension via surfactant secretion, which is highly influenced by the breathing-associated mechanical cues. These spatially heterogeneous mechanical cues have been linked to several physiological and pathophysiological states. Here, we describe the development of a microfluidically assisted lung cell culture model that incorporates heterogeneous cyclic stretching to mimic alveolar respiratory motions. Employing this device, we have examined the effects of respiratory biomechanics (associated with breathing-like movements) and strain heterogeneity on alveolar epithelial cell functions. Furthermore, we have assessed the potential application of this platform to model altered matrix compliance associated with lung pathogenesis and ventilator-induced lung injury. Lung microphysiological platforms incorporating human cells and dynamic biomechanics could serve as an important tool to delineate the role of alveolar micromechanics in physiological and pathological outcomes in the lung.

An In Vitro Microfluidic Alveolus Model to Study Lung Biomechanics

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Decellularization Strategies for Regenerative Medicine: From Processing Techniques to Applications

An In Vitro Microfluidic Alveolus Model to Study Lung Biomechanics