Improving bone defect healing using magnesium phosphate granules with tailored degradation characteristics.

OBJECTIVES: Dental implant placement frequently requires preceding bone augmentation, for example, with hydroxyapatite (HA) or ß-tricalcium phosphate (ß-TCP) granules. However, HA is degraded very slowly in vivo and for ß-TCP inconsistent degradation profiles from too rapid to rather slow are reported. To shorten the healing time before implant placement, rapidly resorbing synthetic materials are of great interest. In this study, we investigated the potential of magnesium phosphates in granular form as bone replacement materials. METHODS: Spherical granules of four different materials were prepared via an emulsion process and investigated in trabecular bone defects in sheep: struvite (MgNH4PO4·6H2O), K-struvite (MgKPO4·6H2O), farringtonite (Mg3(PO4)2) and ß-TCP. RESULTS: All materials except K-struvite exhibited promising support of bone regeneration, biomechanical properties and degradation. Struvite and ß-TCP granules degraded at a similar rate, with a relative granules area of 29% and 30% of the defect area 4 months after implantation, respectively, whereas 18% was found for farringtonite. Only the K-struvite granules degraded too rapidly, with a relative granules area of 2% remaining, resulting in initial fibrous tissue formation and intermediate impairment of biomechanical properties. SIGNIFICANCE: We demonstrated that the magnesium phosphates struvite and farringtonite have a comparable or even improved degradation behavior in vivo compared to ß-TCP. This emphasizes that magnesium phosphates may be a promising alternative to established calcium phosphate bone substitute materials.

Accelerated bone regeneration through rational design of magnesium phosphate cements.

Results of several studies during past years suggested that magnesium phosphate cements (MPCs) not only show excellent biocompatibility and osteoconductivity, but they also provide improved regeneration capacity due to higher solubility compared to calcium phosphates. These findings also highlighted that chemical similarity of bone substitutes to the natural bone tissue is not a determinant factor in the success of regenerative strategies. The aim of this study was to further improve the degradation speed of MPCs for a fast bone ingrowth within a few months. We confirmed our hypothesis, that decreasing the powder-liquid ratio (PLR) of cement results in an increased content of highly soluble phases such as struvite (MgNH4PO4⋅6H2O) as well as K-struvite (MgKPO4⋅6H2O). Promising compositions with a low PLR of 1 g ml-1 were implanted in partially-loaded tibia defects in sheep. Both cements were partially degraded and replaced by bone tissue after 4 months. The degradation speed of the K-struvite cement was significantly higher compared to the struvite cement, initially resulting in the formation of a cell-rich resorption zone at the surface of some implants, as determined by histology. Overall, both MPCs investigated in this study seem to be promising as an alternative to the clinically well-established, but slowly degrading calcium phosphate cements, depending on defect size and desired degradation rate. Whereas the K-struvite cement might require further modification towards a slower resorption and reduced inflammatory response in vivo, the struvite cement appears promising for the treatment of bone defects due to its continuous degradation with simultaneous new bone formation. STATEMENT OF SIGNIFICANCE: Cold setting bone cements are used for the treatment of bone defects that exceed a critical size and cannot heal on their own. They are applied pasty into the bone defect and harden afterwards so that the shape adapts to the individual defect. Magnesium phosphates such as magnesium ammonium phosphate hexahydrate (struvite) belong to a new class of these cold setting bone cements. They degrade much faster than the clinically established calcium phosphates. In this study, a magnesium phosphate that has hardly been investigated so far was implanted into partially-loaded defects in sheeps: Potassium magnesium phosphate hexahydrate. This showed even faster resorption compared to the struvite cement: after 4 months, 63% of the cement was already degraded.

Biological and mechanical performance and degradation characteristics of calcium phosphate cements in large animals and humans.

Calcium phosphate cements (CPCs) have been used to treat bone defects and support bone regeneration because of their good biocompatibility and osteointegrative behavior. Since their introduction in the 1980s, remarkable clinical success has been achieved with these biomaterials, because they offer the unique feature of being moldable and even injectable into implant sites, where they harden through a low-temperature setting reaction. However, despite decades of research efforts, two major limitations concerning their biological and mechanical performance hamper a broader clinical use. Firstly, achieving a degradation rate that is well adjusted to the dynamics of bone formation remains a challenging issue. While apatite-forming CPCs frequently remain for years at the implant site without major signs of degradation, brushite-forming CPCs are considered to degrade to a greater extent. However, the latter tend to convert into lower soluble phases under physiological conditions, which makes their degradation behavior rather unpredictable. Secondly, CPCs exhibit insufficient mechanical properties for load bearing applications because of their inherent brittleness. This review places an emphasis on these limitations and provides an overview of studies that have investigated the biological and biomechanical performance as well as the degradation characteristics of different CPCs after implantation into trabecular bone. We reviewed studies performed in large animals, because they mimic human bone physiology more closely in terms of bone metabolism and mechanical loading conditions compared with small laboratory animals. We compared the results of these studies with clinical trials that have dealt with the degradation behavior of CPCs after vertebroplasty and kyphoplasty.

Meniscal Replacement With a Silk Fibroin Scaffold Reduces Contact Stresses in the Human Knee.

The aim of the current study was to verify if a previously developed silk fibroin scaffold for meniscal replacement is able to restore the physiological distribution of contact pressure (CP) over the articulating surfaces in the human knee joint, thereby reducing peak loads occurring after partial meniscectomy. The pressure distribution on the medial tibial articular surface of seven human cadaveric knee joints was analysed under continuous flexion-extension movements and under physiological loads up to 2,500 N at different flexion angles. Contact area (CA), maximum tibiofemoral CP, maximum pressure under the meniscus and the pressure distribution were analysed for the intact meniscus, after partial meniscectomy as well as after partial medial meniscal replacement using the silk fibroin scaffold. Implantation of the silk fibroin scaffold considerably improved tibiofemoral contact mechanics after partial medial meniscectomy. While the reduced CA after meniscectomy was not fully restored by the silk fibroin scaffold, clinically relevant peak pressures on the articular cartilage surface occurring after partial meniscectomy were significantly reduced. Nevertheless, at high flexion angles static testing demonstrated that normal pressure distribution comparable to the intact meniscus could not be fully achieved. The current study demonstrates that the silk fibroin implant possesses attributes that significantly improve tibiofemoral CPs within the knee joint following partial meniscectomy. However, the failure to fully recapitulate the CAs and pressures observed in the intact meniscus, particularly at high flexion angles, indicates that the implant's biomechanical properties may require further improvement to completely restore tibiofemoral contact mechanics. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 37:2583-2592, 2019.

Articular cartilage and meniscus reveal higher friction in swing phase than in stance phase under dynamic gait conditions.

Most previous studies investigated the remarkably low and complex friction properties of meniscus and cartilage under constant loading and motion conditions. However, both load and relative velocity within the knee joint vary considerably during physiological activities. Hence, the question arises how friction of both tissues is affected by physiological testing conditions occurring during gait. As friction properties are of major importance for meniscal replacement devices, the influence of these simulated physiological testing conditions was additionally tested for a potential meniscal implant biomaterial. Using a dynamic friction testing device, three different friction tests were conducted to investigate the influence of either just varying the motion conditions or the normal load and also to replicate the physiological gait conditions. It could be shown for the first time that the friction coefficient during swing phase was statistically higher than during stance phase when varying both loading and motion conditions according to the physiological gait pattern. Further, the friction properties of the exemplary biomaterial were also higher, when tested under dynamic gait parameters compared to static conditions, which may suggest that static conditions can underestimate the friction coefficient rather than reflecting the in vivo performance.

Surface analysis of sheep menisci after meniscectomy via infrared attenuated total reflection spectroscopy.

Menisci are very important fibrocartilaginous tissue, which maintain biomechanical functions and physiological stabilization of knee joint. Meniscectomy is known as a surgery to recover partial functions from acute meniscus tears. However, the late consequences of total or partial meniscectomy include signs of osteoarthritis and even ligament instability. Infrared attenuated total reflection (IR-ATR) spectroscopy is a very useful technique, which can reveal molecular characteristics via the analysis of vibrational bands. The present study has employed IR-ATR spectroscopy to investigate sheep menisci samples after meniscectomy in a label-free fashion. Several differences of peak absorbance change and peak shift were observed between the native healthy samples and the meniscectomy samples in distinct IR wavenumber regions, such as amide I band, amide II band, C-H bending band as well as the sugar band region. Combining the results from the collagen protein IR spectra, it can be speculated that six months after meniscectomy collagen fibrils on the incision lose its ordered arrangement and a decrease in the triple helical structure of collagen fibril is observed. In addition, the collagen fibrils and proteoglycan content might also be slight varied after meniscectomy.

The challenge of implant integration in partial meniscal replacement: an experimental study on a silk fibroin scaffold in sheep.

PURPOSE: To restore meniscal function after excessive tissue damage, a silk fibroin implant for partial meniscal replacement was developed and investigated in an earlier sheep model. After 6 months implantation, it showed promising results in terms of chondroprotection and biocompatibility. To improve surgical fixation, the material was subjected to optimisation and a fibre mesh was integrated into the porous matrix. The aim of the study was the evaluation of this second generation of silk fibroin implants in a sheep model. METHODS: Nine adult merino sheep received subtotal meniscal replacement using the silk fibroin scaffold. In nine additional animals, the defect was left untreated. Sham surgery was performed in another group of nine animals. After 6 months of implantation macroscopic, biomechanical and histological evaluations of the scaffold, meniscus, and articular cartilage were conducted. RESULTS: Macroscopic evaluation revealed no signs of inflammation of the operated knee joint and most implants were located in the defect. However, there was no solid connection to the remaining peripheral meniscal rim and three devices showed a radial rupture at the middle zone. The equilibrium modulus of the scaffold increased after 6 months implantation time as identified by biomechanical testing (before implantation 0.6 ± 0.3 MPa; after implantation: 0.8 ± 0.3 MPa). Macroscopically and histologically visible softening and fibrillation of the articular cartilage in the meniscectomy- and implant group were confirmed biomechanically by indentation testing of the tibial cartilage. CONCLUSIONS: In the current study, biocompatibility of the silk fibroin scaffold was reconfirmed. The initial mechanical properties of the silk fibroin implant resembled native meniscal tissue. However, stiffness of the scaffold increased considerably after implantation. This might have prevented integration of the device and chondroprotection of the underlying cartilage. Furthermore, the increased stiffness of the material is likely responsible for the partial destruction of some implants. Clinically, we learn that an inappropriate replacement device might lead to similar cartilage damage as seen after meniscectomy. Given the poor acceptance of the clinically available partial meniscal replacement devices, it can be speculated that development of a total meniscal replacement device might be the less challenging option.

Biomechanical, structural and biological characterisation of a new silk fibroin scaffold for meniscal repair.

Meniscal injury is typically treated surgically via partial meniscectomy, which has been shown to cause cartilage degeneration in the long-term. Consequently, research has focused on meniscal prevention and replacement. However, none of the materials or implants developed for meniscal replacement have yet achieved widespread acceptance or demonstrated conclusive chondroprotective efficacy. A redesigned silk fibroin scaffold, which already displayed promising results regarding biocompatibility and cartilage protection in a previous study, was characterised in terms of its biomechanical, structural and biological functionality to serve as a potential material for permanent partial meniscal replacement. Therefore, different quasi-static but also dynamic compression tests were performed. However, the determined compressive stiffness (0.56 ±â€¯0.31 MPa and 0.30 ±â€¯0.12 MPa in relaxation and creep configuration, respectively) was higher in comparison to the native meniscal tissue, which could potentially disturb permanent integration into the host tissue. Nevertheless, µ-CT analysis met the postulated requirements for partial meniscal replacement materials in terms of the microstructural parameters, like mean pore size (215.6 ±â€¯10.9 µm) and total porosity (80.1 ±â€¯4.3%). Additionally, the biocompatibility was reconfirmed during cell culture experiments. The current study provides comprehensive mechanical and biological data for the characterisation of this potential replacement material. Although some further optimisation of the silk fibroin scaffold may be advantageous, the silk fibroin scaffold showed sufficient biomechanical competence to support loads already in the early postoperative phase.