Collagen analogs with phosphorylcholine are inflammation-suppressing scaffolds for corneal regeneration from alkali burns in mini-pigs

Abstract

The long-term survival of biomaterial implants is often hampered by surgery-induced inflammation that can lead to graft failure. Considering that most corneas receiving grafts are either pathological or inflamed before implantation, the risk of rejection is heightened. Here, we show that bioengineered, fully synthetic, and robust corneal implants can be manufactured from a collagen analog (collagen-like peptide-polyethylene glycol hybrid, CLP-PEG) and inflammation-suppressing polymeric 2-methacryloyloxyethyl phosphorylcholine (MPC) when stabilized with the triazine-based crosslinker 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride. The resulting CLP-PEG-MPC implants led to reduced corneal swelling, haze, and neovascularization in comparison to CLP-PEG only implants when grafted into a mini-pig cornea alkali burn model of inflammation over 12 months. Implants incorporating MPC allowed for faster nerve regeneration and recovery of corneal sensation. CLP-PEG-MPC implants appear to be at a more advanced stage of regeneration than the CLP-PEG only implants, as evidenced by the presence of higher amounts of cornea-specific type V collagen, and a corresponding decrease in the presence of extracellular vesicles and exosomes in the corneal stroma, in keeping with the amounts present in healthy, unoperated corneas.

Cardiomyogenic Differentiation Potential of Human Dilated Myocardium-Derived Mesenchymal Stem/Stromal Cells: The Impact of HDAC Inhibitor SAHA and Biomimetic Matrices

“…There is also a possibility that HA, due to its hydrophilicity, could interrupt tight collagen packaging and improve cell binding to the hydrogel and subsequent quicker gene expression [ 72 ]. In addition, the combination of collagen I hydrogels with MPC, a cell membrane mimicking polymer [ 73 ], can regulate cell attachment [ 74 ], and was shown to be successfully used in corneal tissue regeneration [ 30 , 75 ]. Recently, MPC has been also shown to have anti-inflammatory feature that is important for the long-term tissue regeneration purposes [ 30 ].…”

“…In addition, the combination of collagen I hydrogels with MPC, a cell membrane mimicking polymer [ 73 ], can regulate cell attachment [ 74 ], and was shown to be successfully used in corneal tissue regeneration [ 30 , 75 ]. Recently, MPC has been also shown to have anti-inflammatory feature that is important for the long-term tissue regeneration purposes [ 30 ]. Despite the fact that various composition of hydrogel biomatrices have been employed to mimic heart ECM [ 76 ], increase vascularization [ 77 ], deliver small molecules [ 78 ], or conveniently transplanted cells [ 79 ], the interest in complex cardiac tissue engineering techniques is constantly growing.…”

“…Hyaluronic acid (HA) is another most abundant non-proteoglycan, a polysaccharide component of the heart ECM, which in combination with collagen I was successfully used for the rat heart tissue engineering purposes [ 29 ]. Recent study also showed that polymer 2-methacryloyloxyethyl phosphorylcholine (MPC), beside its structural similarity to the cell membrane phospholipids, has anti-inflammatory properties that were used to improve survival of long-term corneal implants [ 30 ]. Moreover, the corneal implants with MPC showed faster eye nerve regeneration and recovery than implants without MPC.…”

A Light‐Curable and Tunable Extracellular Matrix Hydrogel for In Situ Suture‐Free Corneal Repair

“…Then each sample ( N = 3) was incubated in 200 µL of bacterial collagenase type 1 (Sigma, 5 U mL −1 in 50 × 10 −3 m TES and 0.36 × 10 −3 m calcium chloride), as the common protocol to assess the degradability of a developed biomaterial for cornea regeneration. [ 33 ] Each sample was weighted on days 0, 1, 2, 5, and 10 and the weight change (%) was calculated.…”

Recent progress and perspectives in applications of 2-methacryloyloxyethyl phosphorylcholine polymers in biodevices at small scales

“…In addition to the suppression of fouling, MPC polymers also play an additional role in increasing lubrication and softness, which enhances the performance of materials used in orthopedics [92][93][94][95][96][97][98] and ophthalmology. [99][100][101][102][103][104][105][106][107] Most of the grating methods used for coating MPC polymers on orthopedic devices is photo-induced radical polymerization followed by a few reports of thermal-induced radical polymerization 94,96 or the dip-coat method. 108 For instance, Liu et al synthesized poly(MPC-co-dopamine methacrylamide (DMA)) (referred to as DMA-MPC in ref.…”