Infiltration and In-Tissue Polymerization of Photocross-Linked Hydrogel for Effective Fixation of Implants into Cartilage—An In Vitro Study

Abstract

Effective and biocompatible fixation of implants into cartilage defects has yet to be successfully achieved. [Poly-d,l-lactic acid/polyethyleneglycol/poly-d,l-lactic acid] (PDLLA-PEG) is a chondrosupportive scaffold that is photocross-linked using the visible-light photoinitiator lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP). Interestingly, LAP and its monomer DLLA-EG are able to infiltrate the cartilage and form hydrogels upon the detection of light. After the infiltration of LAP and DLLA-EG into the implant and host cartilage, an interconnected and continuous hydrogel structure is formed which fixes the implant within the host cartilage. A mechanical test shows that the infiltrated group displays a significantly higher push-out force than the group that has not been infiltrated (the traditional fibrin fixation group). Surprisingly, the in-cartilage hydrogel also reduces the release of sulfated glycosaminoglycan from cartilage explants. However, infiltration does not affect the cell viability or the expression of cartilage marker genes. This new strategy thus represents a biocompatible and efficient method to fix implants into host tissues.

PEG Reinforced Scaffold Promotes Uniform Distribution of Human MSC-Created Cartilage Matrix

“…The advantage of this method is we can incorporate another type of biomaterials into pre-made scaffolds at any time. We previously found that five minutes of dipping was adequate for PEGDA penetration in a chip of 5 mm diameter and 2 mm height [ 10 ], and herein we demonstrated the stable form of PEG-infiltrated gels with greater mechanical stiffness constructs. In addition, chondrocyte culture in stiffer matrix material was found to be positively impact to chondrogenesis regarding the nature of articular cartilage as a weight-bearing structure [ 15 ].…”

“…A technical challenge was how to include PEG polymers into hBMSCs-loaded GH constructs in the middle of chondrogenesis. We adapted a previous method developed in our lab [ 10 ], in which monomers and photoinitiators were first penetrated into native cartilage and then in situ cured within the tissue. A similar strategy was also reported by other research groups [ 13 , 14 ].…”

“…In order to develop a new scaffold with appropriate mechanical properties to native articular cartilage and the ability to adequately support chondrogenesis, we combined two PEG and GH-based scaffolds. Instead of directly mixing them before polymerization, we adapted the method that we recently used [ 10 ], in which uncured monomer and photoinitiators were infiltrated into pre-formed GH hydrogel and then in situ photopolymerized within cartilage. The new method allowed for the incorporation of uncured poly (ethylene glycol) diacrylate (PEGDA) at the beginning and also at any time during chondrogenesis.…”

Regenerated silk fibroin based on small aperture scaffolds and marginal sealing hydrogel for osteochondral defect repair

“…For example, glycosaminoglycans (GAGs) have been proven to directly hinder cell adhesion [8]; Second, cell death as a result of surgical preparation at the defect edges reduces integration potential [9]. Third, stress concentration occurs when the biomechanical properties of the implants and native tissues are mismatched under forces, damaging the surrounding tissue and weakening integration [10]. Strategies for enhancing lateral integration include anti-apoptosis agents [9], matrix-degrading enzymes [7], and, more recently, scaffold functionalization to enable direct bonding to adjacent cartilage [11].…”

Marginal sealing around integral bilayer scaffolds for repairing osteochondral defects based on photocurable silk hydrogels

“…Lateral integration is exceedingly difficult to achieve for the following reasons: 1) cartilage displays low metabolism and contains dense, anti-adhesive extracellular matrix (ECM) [ 13 ]. For example, proteins transcribed from the proteoglycan 4 (PRG4) gene, contributors to cartilage's low friction, and glycosaminoglycans (GAGs) have been shown to directly inhibit cell adhesion [ 14 ]; 2) the surgical preparation of defects results in cell death at the defect margins, further reducing integration potential [ 15 ]; and 3) upon loading, mismatches between the biomechanical properties of the implanted scaffolds and native cartilage tissue result in stress concentration, diminishing integration and damaging the surrounding tissue [ 8 , 16 ]. Hence, effective strategies to enhance lateral integration are reported rarely, if ever.…”