Peri‐implant bone formation and implant integration strength of peptide‐modified p(AAM‐co‐EG/AAC) interpenetrating polymer network‐coated titanium implants

Abstract

Interpenetrating polymer networks (IPNs) of poly (acrylamide-co-ethylene glycol/acrylic acid) functionalized with an -Arg-Gly-Asp- (RGD) containing 15 amino acid peptides, derived from rat bone sialoprotein (bsp-RGD(15), were grafted to titanium implants in an effort to modulate bone formation in the peri-implant region in the rat femoral ablation model. Bone-implant contact (BIC) and bone formation within the medullary canal were determined using microcomputed tomography at 2 and 4 weeks postimplantation. BIC for bsp-RGD(15)-IPN implants was enhanced relative to hydroxyapatite tricalcium phosphate (HA-TCP) coated implants, but was similar to all other groups. Aggregate bone formation neither indicated a dose-dependent effect of bsp-RGD(15) nor a meaningful trend. Mechanical testing of implant fixation revealed that only the HA-TCP coated implants supported significant (>1 MPa) interfacial shear strength, despite exhibiting lower overall BIC, an indication that bone ingrowth into the rougher coating was the primary mode of implant fixation. While no evidence was found to support the hypothesis that bsp-RGD(15)-modified IPN coated implants significantly impacted bone-implant bonding, these results point to the lack of correlation between in vitro studies employing primary osteoblasts and in vivo wound healing in the peri-implant region.

The effect of integrin-specific bioactive coatings on tissue healing and implant osseointegration

“…As demonstrated in the in vitro analyses (Fig. 3) and previous work (15), binding of α V β 3 suppresses osteoblastic differentiation. Moreover, α v β 3 -overexpressing osteoblasts exhibited impeded mineralization capacity due to suboptimal integrin-matrix interactions, JNK activity, and matrix protein expression [31].…”

“…The most common approach relies on the presentation of the arginine-glycine-aspartic acid (RGD) adhesive sequence derived from FN. While synthetic and natural materials functionalized with RGD oligopeptides support integrin-mediated adhesion, proliferation, and differentiation in vitro, mounting evidence indicates that this biomaterial surface engineering strategy does not enhance biomedical implant integration or function in rigorous animal models [14][15][16]. Based on previous in vitro work demonstrating that integrin binding specificity (α 5 β 1 vs. α V β 3 ) regulates osteoblastic differentiation [17], we hypothesized that the marginal healing responses to RGDfunctionalized implants arise from the lack of selectivity of this ligand for specific integrins.…”

Biomolecular surface coating to enhance orthopaedic tissue healing and integration

“…The most common peptide-based strategy involves the surface deposition of peptides containing the arginineglycine-aspartic acid (RGD) sequence, which mediates cell attachment to several matrix proteins, including fibronectin, vitronectin, osteopontin, and bone sialoprotein. However, these bio-inspired strategies have only yielded marginal increases in implant osseointegration and mechanical fixation [12,15,16]. An explanation for the disappointing results with RGD-functionalized implants is that this peptide, while specific for integrins, lacks selectivity among integrins and therefore triggers non-discriminatory cell attachment.…”

Intramembranous bone regeneration and implant placement using mechanical femoral marrow ablation: rodent models

“…30 and bone ingrowth. 44 In vivo models are advantageous because of inherent limitation of in vitro studies. Several translational end points that are relevant to tissue engineering and implant fixation can be analyzed after mechanical marrow ablation, including behavioral testing, imaging by mCT, mechanical pull-out testing, histology, dynamic histomorphometry, gene expression and biomarkers.…”