Microstructure and biomechanical characteristics of bone substitutes for trauma and orthopaedic surgery.

BACKGROUND: Many (artificial) bone substitute materials are currently available for use in orthopaedic trauma surgery. Objective data on their biological and biomechanical characteristics, which determine their clinical application, is mostly lacking. The aim of this study was to investigate structural and in vitro mechanical properties of nine bone substitute cements registered for use in orthopaedic trauma surgery in the Netherlands. METHODS: Seven calcium phosphate cements (BoneSource®, Calcibon®, ChronOS®, Eurobone®, HydroSet™, Norian SRS®, and Ostim®), one calcium sulphate cement (MIIG® X3), and one bioactive glass cement (Cortoss®) were tested. Structural characteristics were measured by micro-CT scanning. Compression strength and stiffness were determined following unconfined compression tests. RESULTS: Each bone substitute had unique characteristics. Mean total porosity ranged from 53% (Ostim®) to 0.5% (Norian SRS®). Mean pore size exceeded 100 µm only in Eurobone® and Cortoss® (162.2 ± 107.1 µm and 148.4 ± 70.6 µm, respectively). However, 230 µm pores were found in Calcibon®, Norian SRS®, HydroSet™, and MIIG® X3. Connectivity density ranged from 27/cm3 for HydroSet™ to 0.03/cm3 for Calcibon®. The ultimate compression strength was highest in Cortoss® (47.32 MPa) and lowest in Ostim® (0.24 MPa). Young's Modulus was highest in Calcibon® (790 MPa) and lowest in Ostim® (6 MPa). CONCLUSIONS: The bone substitutes tested display a wide range in structural properties and compression strength, indicating that they will be suitable for different clinical indications. The data outlined here will help surgeons to select the most suitable products currently available for specific clinical indications.

Regenerating Critical Size Rat Segmental Bone Defects with a Self-Healing Hybrid Nanocomposite Hydrogel: Effect of Bone Condition and BMP-2 Incorporation.

The aim of the current study is to assess the biological performance of self-healing hydrogels based on calcium phosphate (CaP) nanoparticles and bisphosphonate (BP) conjugated hyaluronan (HA) in a critical size segmental femoral bone defect model in rats. Additionally, these hydrogels are loaded with bone morphogenetic protein 2 (BMP-2) and their performance is compared in healthy and osteoporotic bone conditions. Treatment groups comprise internal plate fixation and placement of a PTFE tube containing hydrogel (HABP -CaP) or hydrogel loaded with BMP-2 in two dosages (HABP -CaP-lowBMP2 or HABP -CaP-highBMP2). Twelve weeks after bone defect surgery, bone formation is analyzed by X-ray examination, micro-CT analysis, and histomorphometry. The data show that critical size, segmental femoral bone defects cannot be healed with HABP -CaP gel alone. Loading of the HABP -CaP gel with low dose BMP-2 significantly improve bone formation and resulted in defect bridging in 100% of the defects. Alternatively, high dose BMP-2 loading of the HABP -CaP gel does not improve bone formation within the defect area, but leads to excessive bone formation outside the defect area. Bone defect healing is not affected by osteoporotic bone conditions.

Comparison of polyetheretherketone versus silicon nitride intervertebral spinal spacers in a caprine model.

Polyetheretherketone (PEEK) is commonly used as a spinal spacer for intervertebral fusion surgery. Unfortunately, PEEK is bioinert and does not effectively osseointegrate into living bone. In contrast, comparable spacers made of silicon nitride (Si3 N4 ) possess a surface nanostructure and chemistry that encourage appositional bone healing. This observational study was designed to compare the outcomes of these two biomaterials when implanted as spacers in an adult caprine model. Lumbar interbody fusion surgeries were performed at two adjacent levels in eight adult goats using implants of PEEK and Si3 N4 . At six-months after surgery, the operative and adjacent spinal segments were extracted and measured for bone fusion, bone volume, bone-implant contact (BIC) and soft-tissue implant contact (SIC) ratios, and biodynamic stability. The null hypothesis was that no differences in these parameters would be apparent between the two groups. Fusion was observed in seven of eight implants in each group with greater bone formation in the Si3 N4 group (52.6%) versus PEEK (27.9%; p = 0.2). There were no significant differences in BIC ratios between PEEK and Si3 N4 , and the biodynamic stability of the two groups was also comparable. The results suggest that Si3 N4 spacers are not inferior to PEEK and they may be more effective in promoting arthrodesis. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 00B: 000-000, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 688-699, 2019.

Local controlled release of corticosteroids extends surgically induced joint instability by inhibiting tissue healing.

BACKGROUND AND PURPOSE: Corticosteroids are intra-articularly injected to relieve pain in joints with osteoarthritis (OA) or acute tissue damage such as ligament or tendon tears, despite its unverified contraindication in unstable joints. Biomaterial-based sustained delivery may prolong reduction of inflammatory pain, while avoiding harmful peak drug concentrations. EXPERIMENTAL APPROACH: The applicability of prolonged corticosteroid exposure was examined in a rat model of anterior cruciate ligament and medial meniscus transection (ACLT + pMMx) with ensuing degenerative changes. KEY RESULTS: Intra-articular injection of a bolus of the corticosteroid triamcinolone acetonide (TAA) resulted in enhanced joint instability in 50% of the joints, but neither instability-induced OA cartilage degeneration, synovitis, nor the OA-related bone phenotype was affected. However, biomaterial microsphere-based extended TAA release enhanced instability in 94% of the animals and induced dystrophic calcification and exacerbation of cartilage degeneration. In healthy joints, injection with TAA releasing microspheres had no effect at all. In vitro, TAA inhibited cell migration out of joint tissue explants, suggesting inhibited tissue healing in vivo as mechanisms for enhanced instability and subsequent cartilage degeneration. CONCLUSIONS AND IMPLICATIONS: We conclude that short-term TAA exposure has minor effects on surgically induced unstable joints, but its extended presence is detrimental by extending instability and associated joint degeneration through compromised healing. This supports a contraindication of prolonged corticosteroid exposure in tissue damage-associated joint instability, but not of brief exposure.

Unfocused shockwaves for osteoinduction in bone substitutes in rat cortical bone defects.

Bone substitutes are frequently used in clinical practice but often exhibit limited osteoinductivity. We hypothesized that unfocused shockwaves enhance the osteoinductivity of bone substitutes and improve osteointegration and angiogenesis. Three different bone substitutes, namely porous tricalcium phosphate, porous hydroxyapatite and porous titanium alloy, were implanted in a critical size (i.e. 6-mm) femoral defect in rats. The femora were treated twice with 1500 shockwaves at 2 and 4 weeks after surgery and compared with non-treated controls. The net volume of de novo bone in the defect was measured by microCT-scanning during 11-weeks follow-up. Bone ingrowth and angiogenesis in the bone substitutes was examined at 5 and 11 weeks using histology. It was shown that hydroxyapatite and titanium both had an increase of bone ingrowth with more bone in the shockwave group compared to the control group, whereas resorption was seen in tricalcium phosphate bone substitutes over time and this was insensitive to shockwave treatment. In conclusion, hydroxyapatite and titanium bone substitutes favour from shockwave treatment, whereas tricalcium phosphate does not. This study shows that osteoinduction and osteointegration of bone substitutes can be influenced with unfocused shockwave therapy, but among other factors depend on the type of bone substitute, likely reflecting its mechanical and biological properties.

In vivo pharmacokinetics of celecoxib loaded endcapped PCLA-PEG-PCLA thermogels in rats after subcutaneous administration.

Injectable thermogels based on poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide) (PCLA-PEG-PCLA) containing an acetyl- or propyl endcap and loaded with celecoxib were developed for local drug release. The aim of this study was to determine the effects of the composition of the celecoxib/PCLA-PEG-PCLA formulation on their in vivo drug release characteristics. Furthermore, we want to obtain insight into the in vitro-in vivo correlation. Different formulations were injected subcutaneously in rats and blood samples were taken for a period of 8 weeks. Celecoxib half-life in blood increased from 5 h for the bolus injection of celecoxib to more than 10 days for the slowest releasing gel formulation. Sustained release of celecoxib was obtained for at least 8 weeks after subcutaneous administration. The release period was prolonged from 3 to 6-8 weeks by increasing the injected volume from 100 to 500 µL, which also led to higher serum concentrations in time. Propyl endcapping of the polymer also led to a prolonged release compared to the acetyl endcapped polymer (49 versus 21 days) and at equal injected dose of the drug in lower serum concentrations. Increasing the celecoxib loading from 10 mg/mL to 50 mg/mL surprisingly led to prolonged release (28 versus 56 days) as well as higher serum concentrations per time point, even when corrected for the higher dose applied. The in vivo release was about twice as fast compared to the in vitro release for all formulations. Imaging of organs of mice, harvested 15 weeks after subcutaneous injection with polymer solution loaded with infrared-780 labelled dye showed no accumulation in any of these harvested organs except for traces in the kidneys, indicating renal clearance. Due to its simplicity and versatility, this drug delivery system has great potential for designing an injectable to locally treat osteoarthritis, and to enable tuning the gel to meet patient-specific needs.

Degradation, intra-articular retention and biocompatibility of monospheres composed of [PDLLA-PEG-PDLLA]-b-PLLA multi-block copolymers.

In this study, we investigated the use of microspheres with a narrow particle size distribution ('monospheres') composed of biodegradable poly(DL-lactide)-PEG-poly(DL-lactide)-b-poly(L-lactide) multiblock copolymers that are potentially suitable for local sustained drug release in articular joints. Monospheres with sizes of 5, 15 and 30µm and a narrow particle size distribution were prepared by a micro-sieve membrane emulsification process. During in vitro degradation, less crystallinity, higher swelling and accelerated mass loss during was observed with increasing the PEG content of the polymer. The monospheres were tested in both a small (mice/rat) and large animal model (horse). In vivo imaging after injection with fluorescent dye loaded microspheres in mice knees showed that monospheres of all sizes retained within the joint for at least 90days, while the same dose of free dye redistributed to the whole body within the first day after intra-articular injection. Administration of monospheres in equine carpal joints caused a mild transient inflammatory response without any clinical signs and without degradation of the cartilage, as evidenced by the absence of degradation products of sulfated glycosaminoglycans or collagen type 2 in the synovial fluid. The excellent intra-articular biocompatibility was confirmed in rat knees, where µCT-imaging and histology showed neither changes in cartilage quality nor quantity. Given the good intra-articular retention and the excellent biocompatibility, these novel poly(DL-lactide)-PEG-poly(DL-lactide)-b-poly(L-lactide)-based monospheres can be considered a suitable platform for intra-articular drug delivery. STATEMENT OF SIGNIFICANCE: This paper demonstrates the great potential in intra-articular drug delivery of monodisperse biodegradable microspheres which were prepared using a new class of biodegradable multi-block copolymers and a unique membrane emulsification process allowing the preparation of microspheres with a narrow particle size distribution (monospheres) leading to multiple advantages like better injectability, enhanced reproducibility and predictability of the in vivo release kinetics. We report not only on the synthesis and preparation, but also in vitro characterization, followed by in vivo testing of intra-articular biocompatibility of the monospheres in both a small and a large animal model. The favourable intra-articular biocompatibility combined with the prolonged intra-articular retention (>90days) makes these monospheres an interesting drug delivery platform. What should also be highlighted is the use of horses; a very accurate translational model for the human situation, making the results not only relevant for equine healthcare, but also for the development of novel human OA therapies.

Osteophilic properties of bone implant surface modifications in a cassette model on a decorticated goat spinal transverse process.

UNLABELLED: This study comparatively evaluated the osteophilic capacity of 17 different surface modifications (i.e. fourteen different chemical modifications via ceramic coatings and three different physical modifications via surface roughness) for titanium (Ti) surfaces. All surface modifications were subjected to physico-chemical analyses and immersion in simulated body fluid (SBF) for coating stability assessment. Subsequently, a bone conduction chamber cassette model on the goat transverse process was used for comparative in vivo analysis based on bone responses to these different surface modifications after twelve weeks. Histological and histomorphometrical analyses in terms of longitudinal bone-to-implant contact percentage (BIC%), relative bone area (BA%) were investigated within each individual channel and maximum bone height (BH). Characterization of the surface modifications showed significant differences in surface chemistry and surface roughness among the surface modifications. Generally, immersion of the coatings in SBF showed net uptake of calcium by thick coatings (>50µm; plasma-sprayed and biomimetic coatings) and no fluctuations in the SBF for thin coatings (<50µm). The histomorphometrical data set demonstrated that only plasma-sprayed CaP coatings performed superiorly regarding BIC%, BA% and BH compared to un-coated surfaces, irrespective of surface roughness of the latter. In conclusion, this study demonstrated that the deposition of plasma-sprayed CaP coating with high roughness significantly improves the osteophilic capacity of titanium surfaces in a chamber cassette model. STATEMENT OF SIGNIFICANCE: For the bone implant market, a large number of surface modifications are available on different types of (dental and orthopedic) bone implants. As the implant surface provides the interface at which the biomaterial interacts with the surrounding (bone) tissue, it is of utmost importance to know what surface modification has optimal osteophilic properties. In contrast to numerous earlier studies on bone implant surface modifications with limited number of comparison surfaces, the manuscript by van Oirschot et al. describes the data of in vivo experiments using a large animal model that allows for direct and simultaneous comparison of a large variety of surface modifications, which included both commercially available and experimental surface modifications for bone implants. These data clearly show the superiority of plasma-sprayed hydroxyapatite coatings regarding bone-to-implant contact, bone amount, and bone height.

Revival of pure titanium for dynamically loaded porous implants using additive manufacturing.

Additive manufacturing techniques are getting more and more established as reliable methods for producing porous metal implants thanks to the almost full geometrical and mechanical control of the designed porous biomaterial. Today, Ti6Al4V ELI is still the most widely used material for porous implants, and none or little interest goes to pure titanium for use in orthopedic or load-bearing implants. Given the special mechanical behavior of cellular structures and the material properties inherent to the additive manufacturing of metals, the aim of this study is to investigate the properties of selective laser melted pure unalloyed titanium porous structures. Therefore, the static and dynamic compressive properties of pure titanium structures are determined and compared to previously reported results for identical structures made from Ti6Al4V ELI and tantalum. The results show that porous Ti6Al4V ELI still remains the strongest material for statically loaded applications, whereas pure titanium has a mechanical behavior similar to tantalum and is the material of choice for cyclically loaded porous implants. These findings are considered to be important for future implant developments since it announces a potential revival of the use of pure titanium for additively manufactured porous implants.

Osteostatin-coated porous titanium can improve early bone regeneration of cortical bone defects in rats.

A promising bone graft substitute is porous titanium. Porous titanium, produced by selective laser melting (SLM), can be made as a completely open porous and load-bearing scaffold that facilitates bone regeneration through osteoconduction. In this study, the bone regenerative capacity of porous titanium is improved with a coating of osteostatin, an osteoinductive peptide that consists of the 107-111 domain of the parathyroid hormone (PTH)-related protein (PTHrP), and the effects of this osteostatin coating on bone regeneration were evaluated in vitro and in vivo. SLM-produced porous titanium received an alkali-acid-heat treatment and was coated with osteostatin through soaking in a 100 nM solution for 24 h or left uncoated. Osteostatin-coated scaffolds contained ∼0.1 µg peptide/g titanium, and in vitro 81% was released within 24 h. Human periosteum-derived osteoprogenitor cells cultured on osteostatin-coated scaffolds did not induce significant changes in osteogenic (alkaline phosphatase [ALP], collagen type 1 [Col1], osteocalcin [OCN], runt-related transcription factor 2 [Runx2]), or angiogenic (vascular endothelial growth factor [VEGF]) gene expression; however, it resulted in an upregulation of osteoprotegerin (OPG) gene expression after 24 h and a lower receptor activator of nuclear factor kappa-B ligand (RankL):OPG mRNA ratio. In vivo, osteostatin-coated, porous titanium implants increased bone regeneration in critical-sized cortical bone defects (p=0.005). Bone regeneration proceeded until 12 weeks, and femurs grafted with osteostatin-coated implants and uncoated implants recovered, respectively, 66% and 53% of the original femur torque strength (97±31 and 77±53 N·mm, not significant). In conclusion, the osteostatin coating improved bone regeneration of porous titanium. This effect was initiated after a short burst release and might be related to the observed in vitro upregulation of OPG gene expression by osteostatin in osteoprogenitor cells. Long-term beneficial effects of osteostatin-coated, porous titanium implants on bone regeneration or mechanical strength were not established here and may require optimization of the pace and dose of osteostatin release.

Bone regeneration performance of surface-treated porous titanium.

The large surface area of highly porous titanium structures produced by additive manufacturing can be modified using biofunctionalizing surface treatments to improve the bone regeneration performance of these otherwise bioinert biomaterials. In this longitudinal study, we applied and compared three types of biofunctionalizing surface treatments, namely acid-alkali (AcAl), alkali-acid-heat treatment (AlAcH), and anodizing-heat treatment (AnH). The effects of treatments on apatite forming ability, cell attachment, cell proliferation, osteogenic gene expression, bone regeneration, biomechanical stability, and bone-biomaterial contact were evaluated using apatite forming ability test, cell culture assays, and animal experiments. It was found that AcAl and AnH work through completely different routes. While AcAl improved the apatite forming ability of as-manufactured (AsM) specimens, it did not have any positive effect on cell attachment, cell proliferation, and osteogenic gene expression. In contrast, AnH did not improve the apatite forming ability of AsM specimens but showed significantly better cell attachment, cell proliferation, and expression of osteogenic markers. The performance of AlAcH in terms of apatite forming ability and cell response was in between both extremes of AnH and AsM. AcAl resulted in significantly larger volumes of newly formed bone within the pores of the scaffold as compared to AnH. Interestingly, larger volumes of regenerated bone did not translate into improved biomechanical stability as AnH exhibited significantly better biomechanical stability as compared to AcAl suggesting that the beneficial effects of cell-nanotopography modulations somehow surpassed the benefits of improved apatite forming ability. In conclusion, the applied surface treatments have considerable effects on apatite forming ability, cell attachment, cell proliferation, and bone ingrowth of the studied biomaterials. The relationship between these properties and the bone-implant biomechanics is, however, not trivial.

Release behavior and intra-articular biocompatibility of celecoxib-loaded acetyl-capped PCLA-PEG-PCLA thermogels.

In this study, we investigated the in vitro and in vivo properties and performance of a celecoxib-loaded hydrogel based on a fully acetyl-capped PCLA-PEG-PCLA triblock copolymer. Blends of different compositions of celocoxib, a drug used for pain management in osteoarthritis, and the acetyl-capped PCLA-PEG-PCLA triblock copolymer were mixed with buffer to yield temperature-responsive gelling systems. These systems containing up to 50 mg celecoxib/g gel, were sols at room temperature and converted into immobile gels at 37 °C. In vitro, release of celecoxib started after a ∼10-day lag phase followed by a sustained release of ∼90 days. The release was proven to be mediated by polymer dissolution from the gels. In vivo (subcutaneous injection in rats) experiments showed an initial celecoxib release of ∼30% during the first 3 days followed by a sustained release of celecoxib for 4-8 weeks. The absence of a lag phase and the faster release seen in vivo were likely due to the enhanced celecoxib solubility in biological fluids and active degradation of the gel by macrophages. Finally, intra-articular biocompatibility of the 50 mg/g celecoxib-loaded gel was demonstrated using µCT-scanning and histology, where no cartilage or bone changes were observed following injection into the knee joints of healthy rats. In conclusion, this study shows that celecoxib-loaded acetyl-capped PCLA-PEG-PCLA hydrogels form a safe drug delivery platform for sustained intra-articular release.

In situ forming acyl-capped PCLA-PEG-PCLA triblock copolymer based hydrogels.

Sustained intra-articular drug delivery opens up new opportunities for targeted treatment of osteoarthritis. In this study, we investigated the in vitro and in vivo properties and performance of a newly developed hydrogel based on acyl-capped PCLA-PEG-PCLA specifically designed for intra-articular use. The hydrogel formulation consisted of a blend of polymers either capped with acetyl, or with 2-(2',3',5',-triiodobenzoyl, TIB) moieties. TIB was added to visualize the gel using µCT, enabling longitudinal quantification of its degradation. Blends containing TIB-capped polymer degraded in vitro (37 °C; pH 7.4 buffer) through dissolution over a period of ~20 weeks, and degraded slightly faster (~12 weeks) after subcutaneous injection in rats. This in vivo acceleration was likely due to active (enzymatic) degradation, shown by changes in polymer composition and molecular weight as well as the presence of macrophages. After intra-articular administration in rats, the visualized gel gradually lost signal intensity over the course of 4 weeks. Good cytocompatibility of acetyl-capped polymer based hydrogel was proven in vitro on erythrocytes and chondrocytes. Moreover, intra-articular biocompatibility was demonstrated using µCT-imaging and histology, since both techniques showed no changes in cartilage quality and/or quantity.

Enhanced bone regeneration of cortical segmental bone defects using porous titanium scaffolds incorporated with colloidal gelatin gels for time- and dose-controlled delivery of dual growth factors.

Porous titanium scaffolds are a promising class of biomaterials for grafting large bone defects, because titanium provides sufficient mechanical support, whereas its porous structure allows bone ingrowth resulting in good osseointegration. To reinforce porous titanium scaffolds with biological cues that enhance and continue bone regeneration, scaffolds can be incorporated with bioactive gels for time- and dose-controlled delivery of multiple growth factors (GFs). In this study, critical femoral bone defects in rats were grafted with porous titanium scaffolds incorporated with nanostructured colloidal gelatin gels. Gels were loaded with bone morphogenetic protein-2 (BMP-2, 3 µg), fibroblast growth factor-2 (FGF-2, 0.6 µg), BMP-2, and FGF-2 (BMP-2/FGF-2, ratio 5:1) or were left unloaded. GF delivery was controlled by fine tuning the crosslinking density of oppositely charged nanospheres. Grafted femurs were evaluated using in vivo and ex vivo micro-CT, histology, and three-point bending tests. All porous titanium scaffolds containing GF-loaded gels accelerated and enhanced bone regeneration: BMP-2 gels gave an early increase (0-4 weeks), and FGF-2 gels gave a late increase (8-12 weeks). Interestingly, stimulatory effects of 0.6 µg FGF-2 were similar to a fivefold higher dose of BMP-2 (3 µg). BMP-2/FGF-2 gels gave more bone outside the porous titanium scaffolds than gels with only BMP-2 or FGF-2, resulted in bridging of most defects and showed superior bone-implant integrity in three-point bending tests. In conclusion, incorporation of nanostructured colloidal gelatin gels capable of time- and dose-controlled delivery of BMP-2 and FGF-2 in porous titanium scaffolds is a promising strategy to enhance and continue bone regeneration of large bone defects.

Selective laser melting-produced porous titanium scaffolds regenerate bone in critical size cortical bone defects.

Porous titanium scaffolds have good mechanical properties that make them an interesting bone substitute material for large bone defects. These scaffolds can be produced with selective laser melting, which has the advantage of tailoring the structure's architecture. Reducing the strut size reduces the stiffness of the structure and may have a positive effect on bone formation. Two scaffolds with struts of 120-µm (titanium-120) or 230-µm (titanium-230) were studied in a load-bearing critical femoral bone defect in rats. The defect was stabilized with an internal plate and treated with titanium-120, titanium-230, or left empty. In vivo micro-CT scans at 4, 8, and 12 weeks showed more bone in the defects treated with scaffolds. Finally, 18.4 ± 7.1 mm(3) (titanium-120, p = 0.015) and 18.7 ± 8.0 mm(3) (titanium-230, p = 0.012) of bone was formed in those defects, significantly more than in the empty defects (5.8 ± 5.1 mm(3) ). Bending tests on the excised femurs after 12 weeks showed that the fusion strength reached 62% (titanium-120) and 45% (titanium-230) of the intact contralateral femurs, but there was no significant difference between the two scaffolds. This study showed that in addition to adequate mechanical support, porous titanium scaffolds facilitate bone formation, which results in high mechanical integrity of the treated large bone defects.

Bone remodelling around a cementless glenoid component.

Post-operative change in the mechanical loading of bone may trigger its (mechanically induced) adaptation and hamper the mechanical stability of prostheses. This is especially important in cementless components, where the final fixation is achieved by the bone itself. The aim of this study is, first, to gain insight into the bone remodelling process around a cementless glenoid component, and second, to compare the possible bone adaptation when the implant is assumed to be fully bonded (best case scenario) or completely loose (worst case scenario). 3D finite element models of a scapula with and without a cementless glenoid component were created. 3D geometry of the scapula, material properties, and several physiological loading conditions were acquired from or estimated for a specific cadaver. Update of the bone density after implantation was done according to a node-based bone remodelling scheme. Strain energy density for different loading conditions was evaluated, weighted according to their frequencies in activities of daily life and used as a mechanical stimulus for bone adaptation. The average bone density in the glenoid increased after implantation. However, local bone resorption was significant in some regions next to the bone-implant interface, regardless of the interface condition (bonded or loose). The amount of bone resorption was determined by the condition imposed to the interface, being slightly larger when the interface was loose. An ideal screw, e.g. in which material fatigue was not considered, was enough to keep the interface micromotions small and constant during the entire bone adaptation simulation.