Photo-Cross-Linkable Methacrylated Gelatin and Hydroxyapatite Hybrid Hydrogel for Modularly Engineering Biomimetic Osteon

Abstract

Modular tissue engineering holds great potential in regenerating natural complex tissues by engineering three-dimensional modular scaffolds with predefined geometry and biological characters. In modular tissue-like construction, a scaffold with an appropriate mechanical rigidity for assembling fabrication and high biocompatibility for cell survival is the key to the successful bioconstruction. In this work, a series of composite hydrogels (GH0, GH1, GH2, and GH3) based on a combination of methacrylated gelatin (GelMA) and hydroxyapatite (HA) was exploited to enhance hydrogel mechanical rigidity and promote cell functional expression for osteon biofabrication. These composite hydrogels presented a lower swelling ratio, higher mechanical moduli, and better biocompatibility when compared to the pure GelMA hydrogel. Furthermore, on the basis of the composite hydrogel and photolithograph technology, we successfully constructed an osteon-like concentric double-ring structure in which the inner ring encapsulating human umbilical vascular endothelial cells (HUVECs) was designed to imitate blood vessel tubule while the outer ring encapsulating human osteoblast-like cells (MG63s) acts as part of bone. During the coculture period, MG63s and HUVECs exhibited not only satisfying growth status but also the enhanced genic expression of osteogenesis-related and angiogenesis-related differentiations. These results demonstrate this GelMA-HA composite hydrogel system is promising for modular tissue engineering.

Enhancement of aptamer immobilization using egg shell-derived nano-sized spherical hydroxyapatite for thrombin detection in neuroclinic

“…Synthetic HA has been extensively applied in biomedical implants [1,2], bone tissue engineering [3,4], drug delivery [5], and stem cell researches [6] owing to its excellent biocompatibility, bioactivity, porous structure and multi-adsorbing sites.…”

Additive Manufacturing of Precision Biomaterials

“…Following this method, a range of tissue‐specific inks were designed, including for cardiac, liver, and skeletal muscle tissues. Another broadly used ECM‐based bioink is gelatin methacryloyl (GelMA), which has been combined with rheological modifier materials such as gellan gum or alginate to improve its printability, or with organic molecules such as hydroxyapatite or gold nanorod to improve its bioactivity. These advances in the design of natural polymer inks for AM provide an attractive complement to inks based on synthetic materials.…”

Nanoreinforced Hydrogels for Tissue Engineering: Biomaterials that are Compatible with Load‐Bearing and Electroactive Tissues

“…Hydroxyapatite is a naturally occurring ceramic that largely constitutes the inorganic phase of bone, and it is also found in other hard tissues such as tooth and cartilage . A large number of ceramic‐based biomaterials have therefore involved the use of hydroxyapatite to closely mimic the structural and elemental framework of natural bone . The corresponding studies have reported a hydroxyapatite‐mediated increase in the expression of bone markers such as osteopontin, osteocalcin, and alkaline phosphatase (ALP), as a consequence of the exceptional and native‐like osteoinductivity of hydroxyapatite .…”

“…To date, a range of nanomaterials, classified broadly as either mineral‐based or conductive nanomaterials, has been synthesized to reinforce the backbone of hydrogels ( Figure ) . Mineral‐based nanomaterials include various clay‐based platelets and ceramic nanoparticles, while conductive nanomaterials are commonly carbon‐based, including carbon nanotubes (CNTs) and graphene . Although much progress has been made to engineer their corresponding nanocomposite hydrogels, most of these systems have not yet fulfilled their grand potential to yield off‐the‐shelf‐engineered organs and tissues.…”