Hybrid hydrogel based on stereocomplex PDLA/PLLA and gelatin for bone regeneration

Abstract

Natural bone is a perfect combination of dense shell cortical bone and porous core spongiosa. Inspired by this gradient structure, we prepared a double‐layered hydrogel with stereocomplex PDLA‐PEG‐PDLA and PLLA‐PEG‐PLLA as the inner porous core and gelatin/nano hydroxyapitite as the outer strengthen shell. Crosslinking of gelatin with natural crosslinker genipin made the shell available for early supporting and the inner physical hydrogel facilitated new bone formation. Successful synthesis of PDLA‐PEG‐PDLA (or PLLA‐PEG‐PLLA) was confirmed by 1H NMR (stands for nuclear magnetic resonance) spectra. The procedure of composite scaffold was monitored with scanning electron microscopy and fourier‐transform infrared spectroscopy. In vitro test with mouse preosteoblast MC3T3‐E1 cells found that the obtained hybrid hydrogels could improve cell adhesion, proliferation, calcium deposition, and upregulate osteogenesis‐related gene expression. Further in vivo experiment on rat calvarial defects also confirmed the capacity of the as‐prepared scaffold to accelerate new bone formation. The above data suggested that this core‐shell hydrogel helpful for nutrient transportation, bony bridging, and osteoconductivity. But how to control the degradation process of the hydrogel and match with new bone formation still remained challenging.

Recent advances in the development of the physically crosslinked hydrogels and their biomedical applications

“…The PDLA/PLLA/Gel/nHA/Gen hydrogel exhibited optimal interconnectivity, vast porosity, and adequate size for nutrient delivery. In vitro tests with mouse MC3T3-E1 pre-osteoblast cells showed that PDLA/PLLA/Gel/nHA/Gen hydrogels improved cell adhesion, cell proliferation, and calcium deposition (Wang, et al, 2020).…”

“…A hybrid hydrogel made of PDLA/PLLA with an outer layer of gelatin/nano hydroxyapatite (PDLA/PLLA/Gel/nHA/Gen) was prepared for bone tissue engineering (Wang, et al, 2020). The PDLA/PLLA/Gel/nHA/Gen hydrogel exhibited optimal interconnectivity, vast porosity, and adequate size for nutrient delivery.…”

Oxygen‐Releasing Hydrogels for Tissue Regeneration

“…[21][22][23][24][25][26][27][28] This adaptability and functionality extend to bone repair, where hydrogel's three-dimensional network structure provides mechanical support at defect sites, facilitates cell migration, proliferation, and differentiation, and enables localized delivery of essential nutrients, accelerating tissue regeneration and promoting stem cell differentiation into osteoblasts. [29][30][31][32][33][34] The integration of nanotechnology with hydrogel systems is advancing comprehensive treatment approaches for bone defects. [35][36][37] Furthermore, in myocardial repair, hydrogel offers localized support and restores normal heart rhythm, with specialized designs preventing adverse ventricular expansion post-myocardial infarction and localized drug supply reducing apoptosis and encouraging tissue regeneration.…”

New Poly(lactic acid)–Hydrogel Core–Shell Scaffolds Highly Support MSCs’ Viability, Proliferation and Osteogenic Differentiation

“…For these reasons, several scaffolds have been realized with stiff thermoplastics, above all biocompatible and biodegradable polyesters, such as poly(lactic acid) (PLA) and poly(ε-caprolactone) (PCL) [ 8 ]. These materials have been combined with bioceramics (e.g., tricalcium phosphate, hydroxyapatite) and/or hydrogels (e.g., gelatin, chitosan, alginate, hyaluronic acid) to enhance the scaffold bioactivity through multiple solutions, including surface-modified polymers [ 9 ], embedded particles/nanoparticles [ 10 , 11 ], co-axial fibers [ 12 , 13 ], interpenetrating/semi-interpenetrating networks [ 14 ] and other composite systems [ 15 , 16 , 17 ]. Moreover, tissue regeneration can be promoted by adding cells and growth factors to the scaffolds [ 18 ].…”