Injectable Alginate Hydrogel Cross-Linked by Calcium Gluconate-Loaded Porous Microspheres for Cartilage Tissue Engineering

Abstract

A great interest has been shown in the injectable scaffolds for cartilage tissue regeneration because it can fill irregularly shaped defects easily through minimally invasive surgical treatments. Herein, we developed a new injectable three-dimensional (3D) alginate hydrogel loaded with biodegradable porous poly(ε-caprolactone)–b-poly(ethylene glycol)–b-poly(ε-caprolactone) microspheres (MPs/Alg) as the calcium gluconate container to cross-link alginate. Suspensions of chondrocytes/alginate and porous microspheres turned into a gel because of the release of calcium gluconate; thus, the injectable composite hydrogels give a 3D scaffold to fit the defects perfectly and integrate the extracellular-matrix-mimicking architecture to efficiently accommodate cartilage cells in situ. Tissue repair in a full-thickness cartilage defect model was controlled at 6, 12, and 18 weeks after the implant by micro-CT and immunohistochemistry to evaluate the healing status. The defect in the MPs/Alg+ cells group achieved an almost complete repair at 18 weeks, and the repaired chondrocytes regained a normal tissue structure. Moreover, the MPs/Alg+ cells-treated group increased the quality of tissue formed, including the accumulated glycosaminoglycan and the uniformly deposited type II collagen. The results point out the promising application of the injectable MPs/Alg-chondrocytes system for cartilage tissue engineering.

The Effects of TGF-β3 on the Proliferation and Function of Encapsulated Costal Cartilage Chondrocytes in Alginate Scaffold

“…Many studies have suggested that TGF-β increases the secretion of extracellular matrix in chondrocytes, but it is controversial whether this growth factor increases or decreases cell growth and proliferation. [30][31][32] In the present study, it has been observed that at 21 days, the secretion of glycosaminoglycan's and aggrecan significantly increased in the TGF-β3 treated group.…”

“…-TGF + TGF Mean of aggrecan production Groups the alginate increases over time. 30,31 This is while other group of studies revealed a decrease of chondrocytes encapsulated in alginate over time. 32 In addition, a group of researchers reported an increase in the proliferation of chondrocytes, influenced by TGF-β but some also observed a decrease in the percent of cells by TGF-β.…”

Controlled formation of polylysinized inner pores in injectable microspheres of low molecular weight poly(lactide-co-glycolide) designed for efficient loading of therapeutic cells

“…Porous microspheres are also able to cover and reside efficiently on defected tissues, thereby regenerating the tissues according to patient-specific anatomy (i.e. body structures) [6]. In addition, they can be implanted in a minimally invasive manner via injection without requiring a serious surgical procedure [7].…”

Synthesis and Characterization of Thermosensitive Poly(N‐Vinyl Caprolactam)‐Grafted‐Aminated Alginate Hydrogels

“…Alg‐containing hydrogels can be obtained by chemically grafting with other polymers by free radical polymerization, photopolymerization or by crosslinking reactions such as esterification, amidation, and amination using crosslinking agents. However, there are some limitations of photopolymerization methods such as the need for the use of photosensitizers and prolonged irradiation . Also, water‐soluble polysaccharides with hydroxyl groups are generally crosslinked using the potentially cytotoxic reagent, glutaraldehyde (GA) .…”