Vascular Endothelial Growth Factor Mimetic Peptide and Parathyroid Hormone (1–34) Delivered via a Blue-Light-Curable Hydrogel Synergistically Accelerate Bone Regeneration

Abstract

Safe and effective biomaterials are in urgent clinical need for tissue regeneration and bone repair. While numerous advances have been made on hydrogels promoting osteogenesis in bone formation, co-stimulation of the angiogenic pathways in this process remains to be exploited. Here, we have developed a gelatin-based blue-light-curable hydrogel system, functionalized with an angiogenic vascular endothelial growth factor (VEGF) mimetic peptide, KLTWQELYQLKYKGI (KLT), and an osteoanabolic peptide, parathyroid hormone (PTH) 1–34. We have discovered that the covalent modification of gelatin scaffold with peptides can modulate the physical properties and biological activities of the produced hydrogels. Furthermore, we have demonstrated that those two peptides orchestrate synergistically and promote bone regeneration in a rat cranial bone defect model with remarkable efficacy. This dual-peptide-functionalized hydrogel system may serve as a promising lead to functional biomaterials in bone repair and tissue engineering.

Spatial‐Selective Volumetric 4D Printing and Single‐Photon Grafting of Biomolecules within Centimeter‐Scale Hydrogels via Tomographic Manufacturing

“…While covalent grafting of biomolecules could have an effect on protein bioactivity, the use of norbornene moieties for thiol-ene photoclick chemistry has previously been shown to enable thiolated protein immobilization, with several growth factors showing maintained bioactivity post immobilization. [48][49][50][51][52] As a proof of concept, we volumetrically grafted VEGF within a tissue-engineered macrochannel, aiming to improve the adhesion and sprouting capacity of human umbilical vein endothelial cells (HUVECs) within an uncoated lumen. VEGF expresses synergistic interactions with the integrin adhesion receptors guiding vessel growth and maturation, as well as endothelial cell survival by the regulation of antiapop- totic factor expression in these cells in vivo.…”

A 3D biomimetic optoelectronic scaffold repairs cranial defects

“…S17E) expression, especially in the connective tissues near the Si films accompanied with stimulation. It is also known that vascularization always accompanies bone regeneration ( 63 ). The influence of our developed scaffold and optical stimulations on the vascularization process requires further investigations.…”

Advancements in drug-loaded hydrogel systems for bone defect repair

“…prepared PEG hydrogel functionalized by αvβ3 integrin targeting peptide (RGD) and loading these with VEGF increased vascularization compared with the RGD hydrogel without VEGF [ 84 ]. Similarly, a gelatin water gel system functionalized with angiogenic vascular endothelial growth factor (VEGF) mimic peptide KLTWQELYQLKYKGI (KLT) and bone anabolic peptide parathyroid hormone (PTH) 1–34 also potentiated a significant effect in promoting bone regeneration in rat skull defect sites [ 85 ].…”

“…Experiments have revealed that delayed, short-term administration of PTH can promote the healing of bone defect allografts by increasing bone formation at the junction of the graft and bone defect [ 89 ]. As mentioned above, hydrogels loaded with PTH (1-34) and KLT help promote bone regeneration [ 85 ]. In the latest research, an environment responsive hydrogel coated with a mesoporous bioactive glass (MBG) scaffold releases PTH by a continuous and pulsatile dual mode, promoting the proliferation, osteogenic differentiation and proliferation of BMSCs, the migration of human umbilical vein endothelial cells (HUVEC).…”