Injectable and thermosensitive TGF-β1-loaded PCEC hydrogel system for in vivo cartilage repair

Abstract

Chondral defects pose a great challenge for clinicians to manage owing to the limited capacity for self-healing. Various traditional approaches have been adopted for the repair of these defects with unsatisfactory results. Cartilage tissue engineering techniques have emerged as promising strategies to enhance regeneration and overcome these traditional shortcomings. The cell-homing based technique is considered the most promising owing to its unique advantages. Thermosensitive hydrogels have been applied as scaffolds for biomedical applications with smart sol–gel response for altering environmental temperature. Transforming growth factor (TGF)-β1 is considered to be capable of promoting chondrogenesis. In this study, a novel TGF-β1-loaded poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) (PCEC) hydrogel was fabricated using simple procedures. Hydrogel characterization, rheological testing, component analysis, and assessment of sol–gel transition, in vitro degradation, and TGF-β1 release confirmed that this material possesses a porous microstructure with favorable injectability and sustained drug release. Full-thickness cartilage defects were induced on rat knees for in vivo cartilage repair for eight weeks. Micro-CT and histological evaluation provided further evidence of the optimal capacity of this novel hydrogel for cartilage regeneration with respect to that of other methods. Moreover, our results demonstrated that the cell-free hydrogel is thermosensitive, injectable, biodegradable, and capable of in vivo cartilage repair and possesses high potential and benefits for acellular cartilage tissue engineering and clinical application in the future.

Increased recruitment of endogenous stem cells and chondrogenic differentiation by a composite scaffold containing bone marrow homing peptide for cartilage regeneration

“…The stability of the biochemical cues exhibited by an engineered tissue scaffold directly impacts its functionality and validity. Previous studies for cartilage regeneration by stem cells homing have focused on the application of chemokines and growth factors, such as transforming growth factor-β3 and -β1 50 , 51 , stromal cell-derived factor-1 52 , 53 , platelet-derived growth factor-AA 54 , and their combined therapy 55 . However, their short half-life in vivo and deleterious side effects should be considered before widespread clinical use 56 .…”

Synthesis, characterization, and cytotoxicity of PCL–PEG–PCL diacrylate and agarose interpenetrating network hydrogels for cartilage tissue engineering

“…Polyethylene glycol (PEG) is a biocompatible and hydrolytically degradable polymer, therefore, PEG derivatives have been widely used in biomaterials and drug delivery. For example, PEC is one of ester-containing PEG used in tissue engineering, [35] nanotechnology [36,37] and protein/ drug controlled delivery [38,39] since the degradation rates can be controlled by the molecular structure of esters and the degree of branching of the PEGs. [40] Traditional acrylate-derivatized PEG (PEGDA) is a polyether-based hydrogel with endgroup acrylate esters, for that reason, its degradation is due to dydrolysis of the end group acrylate esters and oxidation of the ether backbone.…”

In situ Enabling Approaches for Tissue Regeneration: Current Challenges and New Developments

“…Other advances have been made in spinal degenerative disease, for example an in situ injectable chemically crosslinked hydrogel formed by a two-component reaction of liquid silk fibroin with liquid polyurethane at physiological temperature conditions which was shown to fulfill an entire defect, reducing the danger of implant relocation and the subsequent loss of disk height, minimizing the operative trauma (Hu et al, 2017). Efforts were also made in cartilage regeneration using an injectable hydrogel with transforming growth factor (TGF)-β1, which was considered capable of promoting chondrogenesis (Zhou et al, 2017). This study suggests that the new hydrogel possesses advantages for clinical application and should further be studied for its future use in cartilage TE.…”