In recent decades, the incidence of myopia has significantly increased, accounting for 24.32 % to 35.81 % of the global population [1], especially among adolescents, becoming a major public health problem [2,3]. Surgical correction of myopia is receiving increasing attention as the demand for spectacles removal increases and refractive surgery procedures are upgraded [[4], [5], [6], [7]]. Intraocular refractive surgery, i.e., implantation of phakic intraocular lens (PIOL), has become the best choice for patients with high myopia, as it ensures the integrity of the cornea and preserves the original clarity of lens [[8], [9], [10], [11]]. Common PIOL complications include corneal endothelial cell loss, chronic subclinical inflammation, pupillary block glaucoma, etc. [[12], [13], [14]]. Surgical operations such as altering the implantation position and adding aqueous pores have exerted significant roles in averting the occurrence of postoperative complications [15,16]. At present, the most frequently utilized posterior chamber PIOL in clinical settings is implanted in the ciliary sulcus, and part of PIOL may have direct contact with the uvea [17]. Hence, uveal biocompatibility is a crucial factor that researchers must take into account when designing PIOL.

Yang et al. achieved protein rejection and resistance to cell adhesion by amphiphilic ion modification of the intraocular lens (IOL) bulk material to improve uveal compatibility [18]. Huang et al. used plasma technology to graft 2-methacryloyloxyethyl phosphorylcholine (MPC) onto the front surface of a silicone IOL to improve uveal biocompatibility by increasing the hydrophilicity of the front surface only [19]. These studies on the intraocular behavior of lens materials indicate that hydrophilic acrylic materials possess better uveal biocompatibility, while hydrophobic materials exhibit superior capsular biocompatibility [20]. This seemingly contrary conclusion actually reflects the distinct environments that the materials need to confront in the uvea and capsule. The uveal biocompatibility requires the material to reduce the adhesion of proteins and cells, thereby alleviating inflammatory reactions, while the capsule biocompatibility is manifested in the prevention of posterior capsule opacities (PCO) [21,22]. The sandwich theory suggests that allowing a monolayer of lens epithelial cells to grow between the IOL and the posterior capsule, can effectively inhibit the occurrence of PCO [23], accounting for the tight binding formed among the three and the affinity of fibronectin (FN) and collagen [24,25]. Collagen, as the most widely distributed functional protein in mammals, is an important component of the extracellular matrix and has extensive applications in bioengineering technology [26]. In our previous studies, the application of recombinant collagen in alleviating inflammatory responses of blood-contact devices has also been achieved [27]. Moreover, Logie et al. discovered that FN had a potential immunoregulatory effect during the differentiation process of monocytes into macrophages [28]. Therefore, we speculate that PIOL is capable of mitigating inflammatory responses and enhancing uveal biocompatibility after specifically adsorbing FN. In order to avoid protein inactivation and rejection that may result from direct grafting of FN onto the PIOL surface. Inspired by the sandwich theory, a collagen coating had been designed for trapping FN in situ, that is, grafting collagen on the surface of the PIOL, and selectively trapping FN from the patient's aqueous humor through the collagen-binding domain. Compared with the hydrophilic modification of chemical coatings and lens bulk materials, this surface collagen grafting strategy can mimic the extracellular matrix (ECM) microenvironment without affecting the optical properties of the PIOL and the original process, which is beneficial to mitigate the postoperative inflammatory response and the risk of foreign body rejection. In addition, the pre-grafting of collagen on PIOL can occupy adsorption sites and form a ‘bioinert’ interface, effectively inhibiting the non-specific adsorption of other proteins in the atrial fluid.

Therefore, in this work, collagen derived from porcine sclera, which is readily available in large quantities, was grafted covalently onto the surface of poly hydrophilic hydroxyethyl methacrylate (poly-HEMA) material for constructing a uveal biocompatible surface. Briefly, the hydroxyl groups in HEMA are carboxylated by anhydride, and then the carboxyl groups are activated to covalently bond with the amino in the collagen, thereby grafting collagen onto the PIOL surface to obtain PHEMA@col (Scheme 1). The adsorption behaviour of different proteins on the PIOL surface had been simulated in vitro and collagen coating had been found that was able to increase the selective adsorption of FN. In addition, in vitro macrophages adhesion experiments and anti-inflammatory mechanisms studies demonstrated that collagen coating was beneficial in increasing the uveal biocompatibility and reducing the risk of inflammation in the early postoperative recovery when the blood-aqueous barrier was disrupted. The strategy of in-situ capture of FN by collagen coating provides a new material approach for improving the uveal biocompatibility of PIOL.