The role of peptides in bone healing and regeneration: a systematic review

Abstract

BackgroundBone tissue engineering and the research surrounding peptides has expanded significantly over the last few decades. Several peptides have been shown to support and stimulate the bone healing response and have been proposed as therapeutic vehicles for clinical use. The aim of this comprehensive review is to present the clinical and experimental studies analysing the potential role of peptides for bone healing and bone regeneration.MethodsA systematic review according to PRISMA guidelines was conducted. Articles presenting peptides capable of exerting an upregulatory effect on osteoprogenitor cells and bone healing were included in the study.ResultsBased on the available literature, a significant amount of experimental in vitro and in vivo evidence exists. Several peptides were found to upregulate the bone healing response in experimental models and could act as potential candidates for future clinical applications. However, from the available peptides that reached the level of clinical trials, the presented results are limited.ConclusionFurther research is desirable to shed more light into the processes governing the osteoprogenitor cellular responses. With further advances in the field of biomimetic materials and scaffolds, new treatment modalities for bone repair will emerge.

Proteins and Peptides as Important Modifiers of the Polymer Scaffolds for Tissue Engineering Applications—A Review

“…As mentioned above, this pro-adhesive motif occurs mainly in collagen, gelatin, elastin, fibronectin, and laminins. RGD makes up an anchoring place for both α and β integrin receptors, which enhances adhesion and proliferation of many kind of cells [38,115,117,118].…”

“…This peptide comprises -GTPGPQGIAGQRGVV-(-Gly-Thr-Pro-Gly-Pro-Gln-Gly-Ile-Ala-Gly-Gln-Arg-Gly-Val-Val-) amino acid sequence, which is the same as the one existing in the cell-binding region of collagen Type I. P-15 is known to stimulate osteoblast adhesion and proliferation. Moreover, P-15 upregulates osteogenic gene expression of runt-related transcription factor-2 (RUNX2), osterix (OSTRX), and bone sialoprotein (BSP) [117][118][119].…”

“…This peptide belongs to class of self-assembly peptides (SAPs), which amino acids have tendency to spontaneous adopt a β-sheet structure in the presence of monovalent cation solutions or under physiological conditions. Such process results in formation of self-assembled matrices with interwoven nanofibers [117,118]. It was demonstrated that RADA-16-I enhances adhesion and proliferation of keratinocytes, fibroblasts [135], and osteoblasts [136,137].…”

Synthetic cementum protein 1–derived peptide regulates mineralization in vitro and promotes bone regeneration in vivo

“…To date, several peptides have been engineered to regulate the osteogenic response, among which are human parathyroid hormone 1-34 peptide, parathyroid hormone-related peptide, calcitonin gene-related peptide, osteogenic growth peptide, thrombin peptide 508, cell-binding peptide (p15), and GFOGER and RGD peptides. These peptides have shown clinical effectiveness in vitro by stimulating chemotaxis, cell adhesion, osteoblast proliferation, and differentiation and in vivo by stimulating in situ bone healing and augmentation (3). Our findings show that, although the magnitude varied at different concentrations, CEMP-1-p1, stimulated the proliferation of HuPLCs in a similar manner when Figure 5.…”

Non-unions

“…The best way to address this issue is to support the designation and operation of some clinical units and a national and international level to operate as centers of application of advanced biological based therapies utilising tissue engineering techniques. Such strategy will allow these units to develop the necessary experience to refine techniques and develop standardised protocols (19)(20)(21).…”