Degradable RGD-Functionalized 3D-Printed Scaffold Promotes Osteogenesis

To establish an ideal microenvironment for regenerating maxillofacial defects, recent research interests have concentrated on developing scaffolds with intricate configurations and manipulating the stiffness of extracellular matrix toward osteogenesis. Herein, we propose to infuse a degradable RGD-functionalized alginate matrix (RAM) with osteoid-like stiffness, as an artificial extracellular matrix, to a rigid 3D-printed hydroxyapatite scaffold for maxillofacial regeneration. The 3D-printed hydroxyapatite scaffold was produced by microextrusion technology and showed good dimensional stability with consistent microporous detail. RAM was crosslinked by calcium sulfate to manipulate the stiffness, and its degradation was accelerated by partial oxidation using sodium periodate. The results revealed that viability of bone marrow stem cells was significantly improved on the RAM and was promoted on the oxidized RAM. In addition, the migration and osteogenic differentiation of bone marrow stem cells were promoted on the RAM with osteoid-like stiffness, specifically on the oxidized RAM. The in vivo evidence revealed that nonoxidized RAM with osteoid-like stiffness upregulated osteogenic genes but prevented ingrowth of newly formed bone, leading to limited regeneration. Oxidized RAM with osteoid-like stiffness facilitated collagen synthesis, angiogenesis, and osteogenesis and induced robust bone formation, thereby significantly promoting maxillofacial regeneration. Overall, this study supported that in the stabilized microenvironment, oxidized RAM with osteoid-like stiffness offered requisite mechanical cues for osteogenesis and an appropriate degradation profile to facilitate bone formation. Combining the 3D-printed hydroxyapatite scaffold and oxidized RAM with osteoid-like stiffness may be an advantageous approach for maxillofacial regeneration.

Artificial decellularized extracellular matrix improves the regenerative capacity of adipose tissue derived stem cells on 3D printed polycaprolactone scaffolds

Ideal tissue engineering frameworks should be both an optimal biological microenvironment and a shape and stability providing framework. In this study we tried to combine the advantages of cell-derived artificial extracellular matrix (ECM) with those of 3D printed polycaprolactone (PCL) scaffolds. In Part A, both chondrogenic and osteogenic ECMs were produced by human adipose derived stem cells (hASCs) on 3D-printed PCL scaffolds and then decellularized to create cell free functionalized PCL scaffolds, named acPCL and aoPCL respectively. The decellularization resulted in a significant reduction of the DNA content as well as the removal of nuclei while the ECM was largely preserved. In Part B the bioactivation and the effect of the ac/aoPCL scaffolds on the proliferation, differentiation, and gene expression of hASCs was investigated. The ac/aoPCL scaffolds were found to be non-toxic and allow good adhesion, but do not affect proliferation. In the in vitro investigation of cartilage regeneration, biochemical analysis showed that acPCL scaffolds have an additional effect on chondrogenic differentiation as gene expression analysis showed markers of cartilage hypertrophy. The aoPCL showed a large influence on the differentiation of hASCs. In control medium they were able to stimulate hASCs to produce calcium alone and all genes relevant investigated for osteogenesis were significantly higher expressed on aoPCL than on unmodified PCL. Therefore, we believe that ac/aoPCL scaffolds have a high potential to improve regenerative capacity of unmodified PCL scaffolds and should be further investigated.

Elastin-inspired supramolecular hydrogels: A multifaceted extracellular matrix protein in biomedical engineering

The phenomenal advancement in regenerative medicines have led to the development of bioinspired materials to fabricate biomimetic artificial extracellular matrix (ECM) to support cellular survival, proliferation, and differentiation. Researchers have...

Electrospun Nanofibers of Natural and Synthetic Polymers as Artificial Extracellular Matrix for Tissue Engineering

Many types of polymer nanofibers have been introduced as artificial extracellular matrices. Their controllable properties, such as wettability, surface charge, transparency, elasticity, porosity and surface to volume proportion, have attracted much attention. Moreover, functionalizing polymers with other bioactive components could enable the engineering of microenvironments to host cells for regenerative medical applications. In the current brief review, we focus on the most recently cited electrospun nanofibrous polymeric scaffolds and divide them into five main categories: natural polymer-natural polymer composite, natural polymer-synthetic polymer composite, synthetic polymer-synthetic polymer composite, crosslinked polymers and reinforced polymers with inorganic materials. Then, we focus on their physiochemical, biological and mechanical features and discussed the capability and efficiency of the nanofibrous scaffolds to function as the extracellular matrix to support cellular function.

Outlook for Wound Healing Technologies (a Review)

Tissue engineering is a medical science dealing with reproduction of biological tissues and organs. This area of medicine opens avenues for creation of organs and tissues using biomaterials and nanostructures to sustain their development, maintenance and function repair in a living organism. The scope of tissue engineering is an artificial recreation of tissues at the fi nest structural level. Prerequisite requirements are a cell source (a donor), artificial extracellular matrix and growth factor. The first organ, which was extracorporally created and successfully introduced in medical practice, is skin. Recent years have witnessed a major leap in 3D technology for reproduction of biological structures. Increasing attention is being paid towards controlled design and production of 2D–3D structures consisting of biological materials and viable cells, the procedure defined as bioproduction or bioprototyping. Skin substitutes obtained with the bioprototyping technology possess a wide range of medical applications, primarily to compensate for resident skin deficiency in wound healing.

A Bibliometric Review of Artificial Extracellular Matrices Based on Tissue Engineering Technology Literature: 1990 through 2019

Artificial extracellular matrices (aECMs) are an extension of biomaterials that were developed as in-vitro model environments for tissue cells that mimic the native in vivo target tissues’ structure. This bibliometric analysis evaluated the research productivity regarding aECM based on tissue engineering technology. The Web of Science citation index was examined for articles published from 1990 through 2019 using three distinct aECM-related topic sets. Data were also visualized using network analyses (VOSviewer). Terms related to in-vitro, scaffolds, collagen, hydrogels, and differentiation were reoccurring in the aECM-related literature over time. Publications with terms related to a clinical direction (wound healing, stem cells, artificial skin, in-vivo, and bone regeneration) have steadily increased, as have the number of countries and institutions involved in the artificial extracellular matrix. As progress with 3D scaffolds continues to advance, it will become the most promising technology to provide a therapeutic option to repair or replace damaged tissue.

Recent Advances in Natural Gum-Based Biomaterials for Tissue Engineering and Regenerative Medicine: A Review

The engineering of tissues under a three-dimensional (3D) microenvironment is a great challenge and needs a suitable supporting biomaterial-based scaffold that may facilitate cell attachment, spreading, proliferation, migration, and differentiation for proper tissue regeneration or organ reconstruction. Polysaccharides as natural polymers promise great potential in the preparation of a three-dimensional artificial extracellular matrix (ECM) (i.e., hydrogel) via various processing methods and conditions. Natural polymers, especially gums, based upon hydrogel systems, provide similarities largely with the native ECM and excellent biological response. Here, we review the origin and physico-chemical characteristics of potentially used natural gums. In addition, various forms of scaffolds (e.g., nanofibrous, 3D printed-constructs) based on gums and their efficacy in 3D cell culture and various tissue regenerations such as bone, osteoarthritis and cartilage, skin/wound, retinal, neural, and other tissues are discussed. Finally, the advantages and limitations of natural gums are precisely described for future perspectives in tissue engineering and regenerative medicine in the concluding remarks.