*2.1. Materials*

Sodium alginate (ALG, Mn: 1.3 × 10<sup>5</sup> Da), Poloxamer 407 (POL, Mn: 12,600 Da), 1-ethyl-3- (3-dimethylaminopropyl)-carbodiimide (EDC), horseradish peroxidase (HRP), and *N*-hydroxyl succinimide (NHS) were procured from Aladdin Inc (Shanghai, China). Recombinant human IGF-1 and IGF-1 enzyme-linked immunosorbent assay (ELISA) Kit were purchased from PeproTech Inc (Cranbury, NJ, USA) and R&D systems (Minneapolis, MN, USA), respectively. Other reagents and chemicals were of analytical grade and purchased from Sinopharm Inc (Shanghai, China).

SF was produced using Bombyx Mori cocoons according to the reported method [15]. Cocoons were degummed in a Na2CO3 solution (0.02 M) at 100 ◦C for 30 min, and the retrieved silk fibers were rinsed with ultrapure water followed by drying in a ventilated hood. The obtained SF fibers were then dissolved in a LiBr solution (9.3 M) at 60 ◦C with stirring for 5 h, and the prepared solution was dialyzed against distilled water for 2 days using membrane tubes (MW cuto ff: 3500) to remove impurities. The achieved dilute SF solution was further concentrated to varied concentrations by immersing the solution-loaded membrane tubes in a 50% PEG20000 solution, and the concentrated SF solutions were stored at 4 ◦C for further use.

## *2.2. Synthesis of Alginate-Poloxamer Copolymers*

A two-step method was used to synthesize alginate–poloxamer (ALG–POL) copolymers. POL was first modified into monoamine-terminated POL (MATP) following reported methods [26,27], and the obtained MAPT was then grafted onto alginate at a fixed feed mass ratio of alginate to MATP at 1:30 to achieve alginate–poloxamer copolymers. Details for the synthesis of MATP and ALG–POL can be found in the Supplementary Materials.

## *2.3. Preparation of Bioactive Mesoporous Glasses*

Two kinds of porous mesoporous BG NPs (named as MBG-1 and MBG-2, respectively) with di fferent pore-sizes were prepared following reported methods. MBG-1 NPs were prepared as follows [28]. One gram of hexadecyl-trimethylammonium bromide was dissolved in an emulsion consisted of 150 mL of H2O, 2 mL of aqueous ammonia, 40 mL of ethyl ether, 20 mL of ethanol, and 0.1125 g of calcium nitrate (Ca(NO3)2·4H2O). 600 μL of tetraethyl orthosilicate (TEOS) was then added to the mixture at a molar Ca/Si ratio of 15:85. After stirring at 30 ◦C for 4 h, the white sediment was collected by filtration, washed with distilled water, and dried in air at 60 ◦C, and finally, calcined at 550 ◦C for 5 h. The same method was used to prepare MBG-2 NPs with slight modification [29]. The above prepared emulsion was vigorously stirred at room temperature for 30 min, and then, 600 μL of TEOS was added with vigorous stirring at 30 ◦C for 4 h. The resulting precipitate was collected and processed in the same way as that applied to MBG-1 NPs. Parameters for these BG NPs are given in Table 1.


**Table 1.** Parameters for bioactive glass (BG) nanoparticles.

Several IGF-1 solutions in PBS (pH 7.4) with varied concentration of 50 ng/mL (low dose), 100 ng/mL (medium dose), and 150 ng/mL (high dose) were first prepared. In a typical preparation process, 1 mL of any IGF-1 solutions was introduced into a vial with inner protein-resistant coating, and 10 mg of blank MBG-1 or MBG-2 NPs was then added. The mixture was allowed to incubate overnight on an orbital shaker at 37 ◦C. The IGF-1-loaded BG NPs were collected by centrifugation and washed with PBS followed by freeze-drying. The amount of IGF-1 loaded in BG NPs was measured basing on the difference of IGF-1 concentrations in the loading medium before and after soaking BG NPs by using IGF-1 ELISA Kit. Loading efficiency (LE) of BG NPs was calculated by the following equation:

$$\text{LE}(\%) = (M\_0 \% M\_1) \times 100\% \tag{1}$$

where *M*0 is the mass of IGF-1 encapsulated inside NPs, and *M*1 is the feed mass of IGF-1. Parameters for the IGF-1oaded BG NPs are provided in Table 2.


**Table 2.** Parameters for insulin-like growth factor-1 (IGF-1)-loaded BG nanoparticles.

(a) BS*i* (*i* = 1, 2 and 3) sample set was prepared using blank MBG-1 NPs. (b) BL*j* (*j* = 1, 2 and 3) sample set was prepared using blank MBG-2 NPs.
