In vivo evaluation of biofunctionalized implant surfaces with a synthetic peptide (P-15) and its impact on osseointegration. A preclinical animal study

Authors

Christian M. Schmitt, Markus Koepple, Tobias Moest, Konrad Neumann, Tamara Weisel, Karl Andreas Schlegel

Abstract

The overall aim of the study was to investigate a biofunctionalized implant surface with electrochemically deposition of hydroxyapatite and the synthetic peptide (P-15) and its effect on osseointegration.

Three modified implant types of ANKYLOS® C/X implants were used; (1) machined implants used as negative control (M, n = 20), (2) implants with the FRIADENT® plus surface (grit blasted and acid-etched) used as positive control (P, n = 20), and (3) implants with a biomimetic surface consisting of hydroxyapatite and the synthetic 15 aminoacids containing peptide P-15 (BP, n = 40). The implants were randomly inserted in the mandibles of 10 beagle dogs following 4 months after tooth extraction (P1-P4). Three animals were sacrificed 2 and 7 days after implant insertion, respectively, and four animals were sacrificed 6 months post implant insertion. Bone-to-implant contacts (BICs) were analyzed via histomorphometrical analyses at five different region of interests (ROIs); two at the middle part on either side of the implant (ROI 1/4), two at the apical part of the implant at each side (ROI 2/3), and one at the tip of the implant (ROI 5).

All implant surfaces showed a high level of osseointegration and osteoconductivity. The cumulative implant survival rate (CSR) was 93.8%, 100% in the M, 85% in the P, and 95% in the BP group. No statistical difference in BICs at ROI 1/4, 2/3, and 5 could be shown between implant types following 2 and 7 days of healing. BIC values increased in all groups over time. After 6 months of healing the BP group showed superiority in BIC in ROI 2/3 (73.2 ± 15.6%) compared to the P (48.3 ± 10.6%) and M group (66.3 ± 30.2%) with a significant difference between BP and P (P = 0.002).

It is hypothesized, that the surface biofunctionalization improves peri-implant bone formation and remodeling, leading to an increased bone-to implant contact. However, within the limitations of the study set-up no benefit in the early phase of osseointegration could be established for dental implants with P-15 containing surface in this study.

Link to Article

http://dx.doi.org/10.1111/clr.12723

Covalently immobilised type I collagen facilitates osteoconduction and osseointegration of titanium coating implants

Authors

Haiyong Ao, Youtao Xie, Shengbin Yang, Xiaodong Wu, Kai Li, Xuebin Zheng, Tingting Tang

Abstract

Background/Objective

Plasma-sprayed titanium coating (TC) with rough surfaces has been successfully applied in hip or knee prostheses. This study aimed to investigate the osteoconduction and osseointegration of Type I collagen covalently immobilised on TC (TC-AAC) compared with those of TC.

Methods

In vitro, the migration of human mesenchymal stem cells (hMSCs) on TC and TC-AAC was observed by scanning electron microscopy and visualised fluorescent live/dead assay. In vivo, a rabbit model with femur condyle defect was employed, and implants of TC and TC-AAC were embedded into the femur condyles.

Results

Collagen immobilised on TC could promote hMSCs' migration into the porous structure of the TC. Micro computed tomography images showed that bone trabeculae were significantly more abundant around TC-AAC implants than around TC implants. Fluorescence micrographs indicated more active new-bone formation around implants in the TC-AAC group than in the TC group. The measurement of bone–implant contact on histological sections indicated significantly greater osteointegration around TC-AAC implants than around TC ones.

Conclusion

Immobilised Type I collagen could improve the osteoconduction and osseointegration of TC implants.

Link to Article

http://dx.doi.org/10.1016/j.jot.2015.08.005

Alexidine Dihydrochloride Attenuates Osteoclast Formation and Bone Resorption and Protects Against LPS-Induced Osteolysis

Authors

Xiang Zhu MD, Junjie Gao BSc, Pei Y. Ng PhD, An Qin MD, PhD, James H. Steer BSc, Nathan J. Pavlos PhD, Ming H. Zheng MD, PhD, ARCPA, FRACSPath, Yang Dong MD and Tak S. Cheng PhD

Abstract

Aseptic loosening and periprosthetic infection leading to inflammatory osteolysis is a major complication associated with total joint arthroplasty (TJA). The liberation of bacterial products and/or implant-derived wear particles activates immune cells which produce pro-osteoclastogenic cytokines that enhances osteoclast recruitment and activity leading to bone destruction and osteolysis. Therefore agents which prevent the inflammatory response and/or attenuate excessive osteoclast (OC) formation and bone resorption offer therapeutic potential by prolonging the life of TJA implants. Alexidine dihydrochloride (AD) is a bisbiguanide compound commonly used as an oral disinfectant and in contact lens solutions. It possesses anti-microbial, anti-inflammatory and anti-cancer properties however its effects on OC biology are poorly described. Here, we demonstrate that AD inhibits OC formation and bone resorption in vitro and exert prophylatic protection against LPS-induced osteolysis in vivo. Biochemical analysis demonstrated that AD suppressed RANKL-induced activation of MAPKs (ERK, p38 and JNK) leading to the downregulation of NFATc1. Furthermore, AD disrupted F-actin ring formation and attenuated the ability of mature OC to resorb bone. Collectively our findings suggest that AD may be a promising prophylactic anti-osteoclastic/resorptive agent for the treatment of osteolytic diseases caused by excessive OC formation and function.

Link to Article

http://dx.doi.org/10.1002/jbmr.2710

A resorbable antibiotic eluting bone void filler for periprosthetic joint infection prevention

Authors

Zachary Jones, Amanda E. Brooks, Zachary Ferrell, David W. Grainger and Kristofer D. Sinclair

Abstract

Periprosthetic joint infection (PJI) following total knee arthroplasty is a globally increasing procedural complication. These infections are difficult to treat and typically require revision surgery. Antibiotic-loaded bone cement is frequently utilized to deliver antibiotics to the site of infection; however, bone cement is a nondegrading foreign body and known to leach its antibiotic load, after an initial burst release, at subtherapeutic concentrations for months. This work characterized a resorbable, antibiotic-eluting bone void filler designed to restore bone volume and prevent PJI. Three device formulations were fabricated, consisting of different combinations of synthetic inorganic bone graft material, degradable polymer matrices, salt porogens, and antibiotic tobramycin. These formulations were examined to determine the antibiotic's elution kinetics and bactericidal potential, the device's degradation in vitro, as well as osteoconductivity and device resorption in vivo using a pilot rabbit bone implant model. Kirby-Bauer antibiotic susceptibility tests assessed bactericidal activity. Liquid chromatography with tandem mass spectrometry measured antibiotic elution kinetics, and scanning electron microscopy was used to qualitatively assess degradation. Results indicated sustained antibiotic release from all three formulations above the Staphylococcus aureus minimum inhibitory concentration for a period of 5 to 8 weeks. Extensive degradation was observed with the Group 3 formulation after 90 days in phosphate-buffered saline, with a lesser degree of degradation observed in the other two formulations. Results from the pilot rabbit study showed the Group 3 device to be biocompatible, with minimal inflammatory response and no fibrous encapsulation in bone. The device was also highly osteoconductive—exhibiting an accelerated mineral apposition rate.

Link to Article

http://dx.doi.org/10.1002/jbm.b.33513

Riboflavin crosslinked high-density collagen gel for the repair of annular defects in intervertebral discs: An in vivo study

Authors

Peter Grunert, Brandon H. Borde, Sara B. Towne, Yu Moriguchi, Katherine D. Hudson, Lawrence J. Bonassar, Roger Härtl

Abstract

Open annular defects compromise the ability of the annulus fibrosus to contain nuclear tissue in the disc space, and therefore lead to disc herniation with subsequent degenerative changes to the entire intervertebral disc. This study reports the use of riboflavin crosslinked high-density collagen gel for the repair of annular defects in a needle-punctured rat-tail model. High-density collagen has increased stiffness and greater hydraulic permeability than conventional low-density gels; riboflavin crosslinking further increases these properties. This study found that treating annular defects with crosslinked high-density collagen inhibited the progression of disc degeneration over 18 weeks compared to untreated control discs. Histological sections of FITC-labeled collagen gel revealed an early tight attachment to host annular tissue. The gel was subsequently infiltrated by host fibroblasts which remodeled it into a fibrous cap that bridged the outer disrupted annular fibers and partially repaired the defect. This repair tissue enhanced retention of nucleus pulposus tissue, maintained physiological disc hydration, and preserved hydraulic permeability, according to MRI, histological, and mechanical assessments. Degenerative changes were partially reversed in treated discs, as indicated by an increase in nucleus pulposus size and hydration between weeks 5 and 18. The collagen gel appeared to work as an instant sealant and by enhancing the intrinsic healing capabilities of the host tissue.

Link To Article

http://dx.doi.org/10.1016/j.actbio.2015.06.006

The efficacy of a tissue-engineered xenograft in conjunction with sodium hyaluronate carrier in maxillary sinus augmentation: a clinical study

Authors

H.A. Emam, G. Behiri, M. El-Alaily, M. Sharawy

Abstract

PepGen P-15 Putty comprises anorganic bovine bone matrix (ABM) coupled with a synthetic cell-binding peptide, suspended in a sodium hyaluronate carrier. The P-15 portion exhibits a similar structure and properties to the cell-binding region of type I collagen. This study was performed to evaluate ABM/P-15 putty as the sole graft in sinus augmentation. Ten patients for whom both a sinus augmentation and two implants were indicated in the posterior maxilla were enrolled. Bone cores were harvested at 8 and 16 weeks, followed by placement of one implant at 8 weeks and the second at 16 weeks. Twenty collected bone cores were evaluated histologically and by micro-computed tomography. Results showed a significant increase (P < 0.05) in bone mineral density at 8 weeks (0.70 ± 0.13 g/cm3) and 16 weeks (0.97 ± 0.08 g/cm3) in the graft compared to native (control) bone (0.04 ± 0.02 g/cm3). There was no significant difference (P > 0.05) in the percentage bone volume at the two time intervals (PBV 21.14 ± 4.56 at 8 weeks and 26.33 ± 5.60 at 16 weeks). The average increase in bone height at 16 weeks was 10.55 ± 0.53 mm. It is concluded that PepGen P-15 Putty is capable of conducting and accelerating new bone formation and can successfully support dental implants.

Link To Article

http://dx.doi.org/10.1016/j.ijom.2015.04.011