## 1 Introduction  
With the pioneering work of [PERSON] and coworkers in the 1970's who attached polyethylene glycol (PEG) to proteins, a technique referred to as pegylation, the first polymer-protein conjugates were formed [1]. Ever since, biomolecule-polymer hybrids have been thoroughly investigated as they combine the advantages of synthetic polymers such as mechanical properties and convenient processability with the inherent specificity of proteins in biological systems, making these hybrids useful as therapeutic agents, molecular sensors or switches [2; 3; 4]. Altogether, polymer bioconjugates have been used for various applications in biomedicine [5; 6], biotechnology [7; 8], and nanotechnology [9; 10] for instance as switches to control protein activity [11], as molecular sensors [12] or for affinity chromatography to purify immunoglobulins from human plasma [13]. Thereby, different pathways by which proteins can be attached to a polymer support have been described and commonly involve physical adsorption, specific biological recognition, self-assembly, or covalent immobilization [14]. The covalent attachment is usually preferred whenever protein leaching from the support is a major concern. To attach proteins to a polymeric support covalently, the polymer of choice must be modified towards protein-reactive end-groups that facilitate coupling between the polymer and the amino acids in the proteins side chain. Among others, \(N\)-hydroxysuccinimide (NHS)esters are highly activated to nucleophilic addition and are frequently used for protein immobilization onto polymers. However, the disadvantage of this approach is that heterogeneous bioconjugation often occurs due to non-specific coupling with multiple and random amine residues resulting in a significant reduction in bioactivity [15]. Site-specific modifications of amines have been attempted by exploiting the lower p\(K_{\text{a}}\) of the N-terminal \(\alpha\)-amine. However, even if the coupling reaction is conducted under slightly acidic conditions, heterogeneity is often still observed and unpredictable conjugation of multiple chains can take place. The latter can be detrimental to the properties of the biomacromolecule, potentially resulting in reduced enzymatic or receptor-binding activity and/or toxicity [16; 17; 18]. Besides random coupling, also the limited hydrolytic stability is a potential concern for reactions taking place in aqueous media, which hampers the usage of NHS-esters for specific applications [19]. Therefore, other approaches that result in well-defined conjugates have also been explored. One example is the exploitation of thiol-reactive polymers. The sulfhydryl group of cysteine can be employed for such purposes as cysteine is a scarcely occurring amino acid making site-specific bioconjugation feasible [20]. Another approach towards a fully biorthogonal coupling reaction would be the introduction of non-canonical amino acids bearing for instance alkyne or azide functionality to undergo 1,3-dipolar cycloadditon [21], which is conducted using a Cu(I) catalyst and commonly referred as click-chemistry [22]. Catalyst-free [3 + 2] azide-alkyne cycloadditions for covalent modifications of biomolecules have been described exploiting the ring-strain of cyclootypes which enable in-vivo applications [23]. In this work we present a solvent-free process, called reactive gelation [24], to produce (macro)porous polymer scaffolds bearing azide groups on the surface as shown in our previous work [25]. As schematically shown in Figure 1 (first four boxes), the reactive gelation process contains four main steps: the synthesis of polymeric core-shell nanoparticles, their swelling with cross-linker and lipophilic initiator, high-shear aggregation to form porous microclusters, and the post-polymerization step to harden the obtained fractal materials. Each step is fully separated from the others, and allows better control of the final product properties as discussed earlier [26; 27; 28; 29; 30; 31].