Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5625_Библиотеки_им_академика_М_И_Перельмана

In the last decades, the advancement in medical device and biomaterials research gave rise to different strategies to substitute or replace tissues and organs damaged by pathologies or trauma[7]. Several different biomaterials are available on the mar­ket for this purpose, and great efforts are still in place to overcome the current limi­tations to safely apply them in clinics.

Polysaccharides like HA, heparan sulfate (HS), heparin, and chondroitin sulfate (CS) (see Figure8.1) are naturally expressed in all human tissues and organs and contribute to the physical properties and physiological function of the tissues of reference[23]. They have been used in the formulation of bioactive medical devices to perform their natural functions (structural and functional), properly affected by functionalization and crosslinking that modulate the bioactivity and degradation rate[24].

Cutaneous lesions generated by burns, ulcers, or trauma are usually cured with skin grafts; however, if the covering process cannot be immediately performed, biomaterialbased patches are employed to induce the correct recovery and regen­eration of the damaged area[31]. HYAFFbased medical devices have been success­fully employed for the regeneration of cutaneous lesions, and the different esterification degrees and formulation methodologies allow for modulation of the final shape/geometries of the device[32]. HYAFF has also been employed in chon­drogenic tissue engineering applications for its ability to induce cartilage forma­tion[33]. In vitro studies employing 3D HYAFFbased matrices showed the ability of autologous chondrocytes to restore the physiological signatures of hyaline carti­lage[34], whereas invivo studies demonstrated that seeding with autologous chon­drocytes induces native cartilage tissue formation with optimal integration in the surrounding tissue[33]. Hyalograft C, a medical device based on cartilage autograft obtained from patient chondrocytes cultured on HYAFF, was introduced for surgi­cal arthroscopic techniques in 1999 [35, 36]. In 2013, following an European Medicines Agency (EMA) report on manufacturing practices, Hyalograft C was withdrawn from the European market[37]. Today, methodologies for treatment of cartilage include new approaches in which autologous chondrocytes are delivered into damaged tissues with HA or collagenbased injectable biomaterials[38]. HA is also employed, in different formulations, in ophthalmic viscoelastic devices (OVDs) or dermatological therapies[39]. The first use of untreated HA in ophthalmic sur­gery was reported in cornea transplantation and, today, it is currently employed in ocular surgeries for corneal protection and vitreous replacement [40]. Food and Drug Administration (FDA) approved the first viscosurgical device based on HA in

material device fields for different applications, even if, considering its main role as an anticoagulant, the use of heparinbased medical devices is mainly focused on bloodcontacting materials[61, 62]. Temporary or permanent devices like hemodi­alysis catheters, coronary or vascular stents and grafts, bypass devices, and extracor­poreal circulation devices exploit heparincoated materials[57, 62–64]. The two general methods employed for the development of heparincoated devices are based on eluting technologies and noneluting technologies. Eluting technologies include all the approaches in which heparin is released in a controlled way, taking advan­tage of noncovalent coatings based on physical or ionic interactions [62, 65, 66]. These methods are employed when heparin delivery is needed to prevent acute and local devicerelated blood clots. The other approach is based on the covalent func­tionalization of the medical device surface with heparin[67, 68]. This approach is desirable when longterm thromboresistance is needed at the material surface. Different conjugation methodologies exploit the direct coupling of complementary functional groups already present in heparin and the material surface counterpart, or alternatively introduce new chemoselective orthogonal functional groups and properly tailored linkers to better control heparin exposition and consequently the antithrombotic activity. The chemical nature of the medical device will influence the choice in light of the functional groups eventually present at the surface or, alternatively, introducible upon proper treatment. The most employed conjugation methodologies are based on carbodiimide chemistry, exploiting the carboxyl group of heparin, or oxidation mediated by periodate, for controlled oxidative degradation to generate some aldehydes[69]. A coating material based on heparin, polyethylene oxide, and sulphonate groups covalently conjugated to hydrophilic modified poly-

, developed by Jostra AG and now a property of Maquet Medical, a material obtained with heparin linked to human albumin employed for coating vascular grafts and cardiopulmonary bypass[63, 70]. The conjugation of heparin to polyamine carriers, performed by introducing etherofunctional crosslinkers, is currently employed as Corline Heparine Surface Technology, developed by Corline System AB. Many other coating methodologies employed for the modification of medical device surfaces to control the interface between blood components and material surface, and to minimize blood clot formation and thrombolytic events are reported with other commercial examples in Table8.1.

The large availability of polysaccharides derived from plants, algae, and animals and the possibility to produce them by microbial fermentation make them very attractive and cheaper starting materials[13]. Several studies are focused on the biocompatibility of such polysaccharides, and many of them are already in clinical applications. These polysaccharides present an interesting variety of biochemical and physical properties that can eventually be advantageously exploited in

biomedical applications. Furthermore, they can be properly modified to control the properties and final morphologies of a large plethora of formulations. The main nonhuman polysaccharides exploited for biomedical devices are alginates, carra­geenan, and fucoidan (derived from algae), dextran, pullulan, and gellan (derived from microbes), and chitosan (derived from animals) (see Figure8.3).