Drug‐Loaded Elastin‐Like Polypeptide–Collagen Hydrogels with High Modulus for Bone Tissue Engineering

Abstract

Emphasizing the role of hydrogel stiffness and cellular differentiation, this study develops collagen and elastin-like polypeptide (ELP)-based bone regenerative hydrogels loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) and doxycycline with mechanical properties suitable for osteogenesis. The drug-incorporated collagen-ELP hydrogels has significantly higher modulus of 35 ± 5 kPa compared to collagen-only hydrogels. Doxycycline shows a bi-phasic release with an initial burst release followed by a gradual release, while rhBMP-2 exhibits a nearly linear release profile for all hydrogels. The released doxycycline shows anti-microbial activity against Pseudomonas aeruginosa, Streptococcus sanguinis, and Escherichia coli. Microscopic observation of the hydrogels reveals their interconnected, macroporous, 3D open architecture with pore diameters between 160 and 400 µm. This architecture supports human adipose-derived stem cell attachment and proliferation from initial days of cell seeding, forming a thick cellular sheath by day 21. Interestingly, in collagen and collagen-ELP hydrogels, cell morphology is elongated with stretched slender lamellipodial formation, while cells assemble as spheroidal aggregates in crosslinked as well as drugloaded hydrogels. Osteogenic markers, alkaline phosphatase and osteocalcin, are expressed maximally for drug-loaded hydrogels compared to those without drugs. The drug-loaded collagen-ELP hydrogels are thus promising for combating bacterial infection and promoting guided bone regeneration. 2 of 13) www.advancedsciencenews.com www.mbs-journal.de (

Sodium alginate/collagen composite multiscale porous scaffolds containing poly(ε-caprolactone) microspheres fabricated based on additive manufacturing technology

“…[13][14][15][16][17][18] Moreover, the hydrophilic collagen scaffolds have difficulty loading hydrophobic drugs uniformly, which limits the application of collagen scaffold materials in drug loading and sustained release. 19,20 In addition, currently most of the prepared collagen scaffolds consist of singlepore structures, which do not satisfy the pore requirements for the multi-scale porous structures of cartilage. 21,22 For improving the mechanical properties of collagen scaffolds, adding suitable crosslinking agent, inlaying rigid particles and introducing double crosslinking network into collagen hydrogels are promising effective methods.…”

Elastin-Collagen Based Hydrogels as Model Scaffolds to Induce Three-Dimensional Adipocyte Culture from Adipose Derived Stem Cells

“…ELP with a primary sequence (valine-proline-glycine-valine-glycine) 120 was produced as detailed before [ 19 , 20 , 21 ]. Type I collagen (rat tail tendon; ~9 mg/mL) was purchased from ThermoFisher Scientific, Waltham, MA.…”

“…Physical characterizations were performed using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, scanning electron microscopy (SEM), and measurement of swelling ratio as detailed elsewhere [ 19 ]. ATR-FTIR was performed using a Spectrum 100 FT-IR spectrophotometer (PerkinElmer, Waltham, MA, USA) on freeze-dried scaffolds ( n = 3) at 4 cm −1 resolution.…”

“…Mechanical characterization was performed using uniaxial compression testing on hydrated scaffold samples ( n = 5) using Sintech 2/G Materials Testing System (MTS, Eden Prairie, MN, USA) as detailed before [ 19 ]. A strain rate of 1 mm/min until 50% strain was used on scaffold samples placed in a 48-well tissue culture polystyrene plate in a confined manner at room temperature.…”

“…Elastin-like polypeptides (ELPs) and silk-like polypeptides are two examples of widely-used peptide-based biomaterials [ 13 ]. We previously prepared composite hydrogels using type I collagen as a minority component (<30% w/w ) and ELP as the majority component (>70% w/w ) [ 19 , 20 , 21 ]. ELPs are a family of peptide-based natural polymers that can be genetically engineered, which eliminates batch-to-batch variation, and their amino acid sequence is derived from the mammalian elastin [ 22 ].…”