A novel calcium‐accumulating peptide/gelatin in situ forming hydrogel for enhanced bone regeneration

Abstract

Bioactive agents, including proteins and peptides, can be loaded into hydrogels to improve bone regenerative capacity with their controlled release. However, the current loading method has focused on physical mixing, which has limited release control. Therefore, alternative conjugation of bioactive agents with hydrogels is highly recommended. Direct chemical conjugation of synthetic peptides containing a functional moiety with a hydrogel would be ideal. Here, we synthesized a bioactive calcium accumulating peptide (CAP) containing a collagen binding motif, which can induce osteogenic differentiation. A tyrosine residue in CAP was used to directly chemically conjugate the peptide with a gelatin-based enzymatically crosslinked hydroxyphenyl propionic acid hydrogel under H O /Horse radish peroxidase conditions. To test the acceleration of bone formation, human periodontal ligament stem cells (PDLSCs) were loaded into a chemically conjugated CAP hydrogel. The CAP hydrogel induced bone mineralization around the PDLSCs and increased osteogenic marker expressions in vitro. It also recovered a bone layer in a calvarial defect 4 weeks postimplantation. In summary, an injectable CAP hydrogel scaffold system was developed as a potentially useful engineered microenvironment to enhance bone restoration, and it could be utilized as a vehicle for bioactive delivery of stem cells in tissue regenerative therapy. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 531-542, 2018.

Identification of cell‐penetrating osteogenic peptide from copine‐7 protein and its delivery system for enhanced bone formation

“…The female ICR mice (8‐week‐old; 30~40 g) which were raised in specific‐pathogen‐free environment, were anesthetized by intraperitoneal injection with a mixture of Zoletil (0.6 mL/kg) and Rompun (0.4 mL/kg). The surgery for calvarial defects was conducted as previously reported (Jo et al, ). The defect size was created with 5 mm diameter.…”

Hydrogel as a Biomaterial for Bone Tissue Engineering: A Review

“…Lohmann et al [ 113 ] used the critical-size calvarial bone defect, with an 8 mm diameter defect surgically created in the parietal bone in rats, to evaluate the healing potency of the porous hydrogel. Rodent experimental animals used in the calvarial bone defect model are inexpensive, easy to house, and the bone structure allows for the generation of a standardized defect that can be analyzed using histology and radiographic analysis [ 114 ]. The disadvantages of the calvarial defect model are that it is unable to evaluate the performance of materials under physiological mechanical load; the rodent animals have a short lifespan, which is not suitable for long-term research; and the biopsies or blood samples are relatively small [ 99 ].…”

Horseradish peroxidase-catalyzed hydrogelation of fish gelatin with tunable mechanical properties and biocompatibility

“…The covalently cross-linked gelatin-based hydrogels have been widely studied for various tissue regeneration applications, such as wound dressing, neural regeneration, or bone grafts, due to their favorable properties, including high mechanical strength and stability. 6–10 Different approaches, such as Michael additions, 11 Schiff-based reactions, 12 “click” chemistry, 4 or UV irradiation 13 have been reported for the in situ formation of gelatin-based hydrogels. However, these approaches required multistep syntheses or the addition of chemical cross-linkers, which may cause potential toxicity from synthesized precursors and cross-linkers upon hydrogel’s degradation.…”