Kaushik Mukherjee

Long-term biological fixation and stability of uncemented acetabular implant are influenced by peri-prosthetic bone ingrowth which is known to follow the principle of mechanoregulatory tissue differentiation algorithm. A tissue differentiation is a complex set of cellular events which are largely influenced by various mechanical stimuli. Over the last decade, a number of cell-phenotype specific algorithms have been developed in order to simulate these complex cellular events during bone ingrowth. Higher bone ingrowth results in better implant fixation. It is hypothesized that these cellular events might influence the peri-prosthetic bone ingrowth and thereby implant fixation. Using a three-dimensional (3D) microscale FE model representing an implant-bone interface and a cell-phenotype specific algorithm, the objective of the study is to evaluate the influences of various cellular activities on peri-prosthetic tissue differentiation. Consequently the study aims at identifying those cellular activities that may enhance implant fixation.

The 3D microscale implant-bone interface model, comprising of Porocast Bead of BHR implant, granulation tissue and bone, was developed and meshed in ANSYS (Fig. 1b). Frictional contact (µ=0.5) was simulated at all interfaces. The displacement fields were transferred and prescribed at the top and bottom boundaries of the microscale model from a previously investigated macroscale implanted pelvis model (Fig. 1a) [4]. Periodic boundary conditions were imposed on the lateral surfaces. Linear elastic, isotropic material properties were assumed for all materials. Young's modulus and Poisson's ratios of bone and implant were mapped from the macroscale implanted pelvis [4]. A cell-phenotype specific mechanoregulatory algorithm was developed where various cellular activities and tissue formation were modeled with seven coupled differential equations [1, 2]. In order to evaluate the influence of various cellular activities, a Plackett-Burman DOE scheme was adopted. In the present study each of the cellular activity was assumed to be an independent factor. A total of 20 independent two-level factors were considered in this study which resulted in altogether 24 different combinations to be investigated. All these cellular activities were in turn assumed to be regulated by local mechanical stimulus [3]. The mechano-biological simulation was run until a convergence in tissue formation was attained.

The cell-phenotype specific algorithm predicted a progressive transformation of granulation tissue into bone, cartilage and fibrous tissue (Fig. 1c). Various cellular activities were found to influence the time to reach equilibrium in tissue differentiation and, thereby, attainment of sufficient implant fixation (Fig. 2, Table 1). Negative regression coefficients were predicted for the significant factors, differentiation rate of MSCs and bone matrix formation rate, indicating that these cellular activities favor peri-prosthetic bone ingrowth by facilitating rapid peri-prosthetic bone ingrowth. Osteoblast differentiation rate, on the contrary, was found to have the highest positive regression coefficient among the other cellular activities, indicating that an increase in this cellular activity delays the attainment of equilibrium in bone ingrowth prohibiting rapid implant fixation.

Implant-induced bone remodeling has been identified as a potential reason behind aseptic loosening of uncemented acetabular cups. Using three-dimensional Finite Element models of intact and implanted pelvis, in combination with bone remodeling algorithm, the present study aims at gaining an insight into the evolutionary bone adaptation around a press-fit uncemented acetabular component. Eight static load
cases of normal walking cycle, modeled by 21 muscle forces and hip joint reaction force, were considered in the present study in order to investigate deviation in load transfer due to implantation and peri-acetabular bone adaptation. Based on the results of the present study, a press-fit acetabular component was found to increase load transfer through acetabular cortex. Consequently, predominant bone apposition was observed within the acetabular peripheral cancellous bone. However, a reduction in the density of cancellous bone near the acetabular pole was also observed.

Several mechanobiology algorithms have been employed to simulate bone ingrowth around porous coated implants. However, there is a scarcity of quantitative comparison between the efficacies of commonly used mechanoregulatory algorithms. The objectives of this study are: (1) to predict peri-acetabular bone ingrowth using cell-phenotype specific algorithm and to compare these predictions with those obtained using phenomenological algorithm and (2) to investigate the influences of cellular parameters on bone ingrowth. The variation in host bone material property and interfacial micromotion of the implanted pelvis were mapped onto the microscale model of implant–bone interface. An overall variation of 17–88 % in peri-acetabular bone ingrowth was observed. Despite differences in predicted tissue differentiation patterns during the initial period, both the algorithms predicted similar spatial distribution of neo-tissue layer, after attainment of equilibrium. Results indicated that phenomenological algorithm, being computationally faster than the cell-phenotype specific algorithm, might be used to predict peri-prosthetic bone ingrowth. The cell-phenotype specific algorithm, however, was found to be useful in numerically investigating the influence of alterations in cellular activities on bone ingrowth, owing to biologically related factors. Amongst the host of cellular activities, matrix production rate of bone tissue was found to have predominant influence on peri-acetabular bone ingrowth.

Fixation of uncemented implant is influenced by peri-prosthetic bone ingrowth, which is dependent on the mechanical environment in the implant-bone structure. The objective of the study is to gain an insight into the tissue differentiation around an acetabular component. A mapping framework has been developed to simulate appropriate mechanical environment in the three-dimensional microscale model, implement the mechanoregulatory tissue differentiation algorithm and subsequently assess spatial distribution of bone ingrowth around an acetabular component, quantitatively. The FE model of implanted pelvis subjected to eight static load cases during a normal walking cycle was first solved. Thereafter, a mapping algorithm has been employed to include the variations in implant-bone relative displacement and host bone material properties from the macroscale FE model of implanted pelvis to the microscale FE model of the beaded implant-bone interface. The evolutionary tissue differentiation was observed in each of the 13 microscale models corresponding to 13 acetabular regions. The total implant-bone relative displacements, averaged over each region of the acetabulum, were found to vary between 10 and 60μm. Both the linear elastic and biphasic poroelastic models predicted similar mechanoregulatory peri-prosthetic tissue differentiation. Considerable variations in bone ingrowth (13 – 88%), interdigitation depth (0.2 – 0.82mm) and average tissue Young’s modulus (970 – 3430MPa) were predicted around the acetabular cup. A gradual increase in the average Young’s modulus, interdigitation depth and decrease in average radial strains of newly formed tissue layer were also observed. This scheme can be extended to investigate tissue differentiation for different surface texture designs on the implants.

Peri-acetabular bone ingrowth plays a crucial role in long-term stability of press-fit acetabular
cups. A poor bone ingrowth often results in increased cup migration, leading to aseptic loosening of the
implant. The rate of peri-prosthetic bone formation is also affected by the polar gap that may be introduced
during implantation. Applying a mechano-regulatory tissue differentiation algorithm on a two-dimensional
plane strain microscale model, representing implant-bone interface, the objectives of the study are to gain an
insight into the process of peri-prosthetic tissue differentiation and to investigate its relationship with
implant-bone relative displacement and size of the polar gap. Implant-bone relative displacement was found
to have a considerable influence on bone healing and peri-acetabular bone ingrowth. An increase in implantbone
relative displacement from 20 µm to 100 µm resulted in an increase in fibrous tissue formation from
22% to 60% and reduction in bone formation from 70% to 38% within the polar gap. The increase in fibrous
tissue formation and subsequent decrease in bone formation leads to weakening of the implant-bone
interface strength. In comparison, the effect of polar gap on bone healing and peri-acetabular bone ingrowth
was less pronounced. Polar gap up to 5 mm was found to be progressively filled with bone under favourable
implant-bone relative displacements of 20 µm along tangential and 20 µm along normal directions.
However, the average Young’s modulus of the newly formed tissue layer reduced from 2200 MPa to 1200
MPa with an increase in polar gap from 0.5 mm to 5 mm, suggesting the formation of a low strength tissue
for increased polar gap. Based on this study, it may be concluded that a polar gap less than 0.5 mm seems
favourable for an increase in strength of the implant-bone interface.

Peri-prosthetic bone ingrowth influences the long-term fixation and stability of uncemented acetabular implant. The objective of the study is to develop a three-dimensional (3-D) microscale FE model representing an implant-bone interface and to investigate the effects of implant-bone relative displacements and interface conditions on peri-prosthetic bone ingrowth using a mechano-regulatory algorithm. A 3-D microscale model of implant-bone interface, representing Porocast Bead of BHR implant, granulation tissue and bone, was developed and meshed in ANSYS (Fig. 1a). Both debonded (with friction coefficient μ=0.5) and bonded interfaces were taken into consideration. Three different levels of displacement fields at the top and bottom boundary of the microscale model were transferred and prescribed from a previously investigated macroscale implanted pelvis model [1]. Periodic boundary conditions were imposed on the lateral surfaces. Linear elastic, homogeneous isotropic material properties were assumed for all materials. Young’s modulus and Poisson’s ratios of bone and implant were mapped from the macroscale implanted pelvis. Tissue differentiation within the granulation tissue was modeled using a sequential, mechano-regulatory algorithm. Depending upon the local mechanical stimulus, comprising of hydrostatic pressure and deviatoric strain, the migrated and proliferated mesenchymal stem cells differentiate into different connective tissue phenotypes. The mechano-biological simulation was run for a post-operative period of two years. Results predicted progressive transformation of granulation tissue into bone, cartilage and fibrous tissue (Fig. 1b). The debonded interface model with higher implant-bone relative displacement predicted ~40% bone formation in inter-bead spacing, which is similar to earlier clinical investigations. An increase in the overall bone ingrowth for all interface conditions was also observed with a reduction in implant-bone relative displacement, which was similar to earlier 2-D FE predictions with debonded interface. However, bonded interface condition was found to predict quantitatively lower bone formation as compared to the debonded interface. The progressive increase in stiffness of the newly formed peri-prosthetic tissue layer was found to follow the characteristic S-shape. The 3-D FE microscale model of implant-bone interface is useful to gain an insight in the peri-prosthetic bone formation. Both debonded and bonded interface conditions predicted reduction in bone formation with an increase in implant-bone relative displacement.

Long-term biological fixation and stability of uncemented acetabular implant are influenced by peri-prosthetic
bone ingrowth which is known to follow the principle of mechanoregulatory fracture healing. Over the last two
decades, several algorithms, broadly classified as cell-phenotype specific [1,2] and phenomenological [3], have
been developed to quantitatively assess the tissue formation in the fracture callus. However, the efficacy of these
algorithms to predict bone ingrowth, with regard to evolutionary mechanical properties of the implant-bone
interfacial layer, is yet to be investigated. Using a three-dimensional (3D) microscale FE model representing an
implant-bone interface, the objective of the study is to quantitatively compare the cell-phenotype specific and
phenomenological mechanoregulatory algorithms for different implant-bone relative displacements.
The 3D microscale implant-bone interface model, comprising of Porocast Bead of BHR implant, granulation
tissue and bone, was developed and meshed in ANSYS (Fig. 1b). Frictional contact (μ=0.5) was simulated at all
interfaces. Three different levels of displacement fields, at the top and bottom boundaries of the microscale
model, were transferred and prescribed from a previously investigated macroscale implanted pelvis model (Fig.
1a) [4]. Periodic boundary conditions were imposed on the lateral surfaces. Linear elastic, isotropic material
properties were assumed for all materials. Young’s modulus and Poisson’s ratios of bone and implant were
mapped from the macroscale implanted pelvis [4]. Two sequential mechanoregulatory tissue differentiation
algorithms, cell-phenotype specific ([1, 2] and phenomenological [3], were developed in order to model the
tissue formation within the interbead spaces. In cell-phenotype specific algorithm (, various cellular activities
and tissue formation were modeled with seven coupled differential equations [1, 2]. However, in
phenomenological algorithm [3], all the cellular activities and tissue formation were indirectly combined and
modeled using a single diffusion equation. Both the algorithms assumed various cellular activities to be
regulated by local mechanical stimulus. The mechano-biological simulation was run for a post-operative period
of two years.
Both the algorithms predicted progressive transformation of granulation tissue into bone, cartilage and fibrous
tissue (Fig. 1c). However, bone formation and average tissue stiffness predicted by cell-phenotype specific
algorithm were found to be 2 – 5% lower than those predicted by phenomenological algorithm. The
phenomenological algorithm with higher implant-bone relative displacement predicted ~40% bone formation in
inter-bead spacing, which is similar to earlier clinical investigations. Both the algorithms predicted an increase in
the overall bone ingrowth with a reduction in implant-bone relative displacement. The progressive increase in
stiffness of the newly formed peri-prosthetic tissue layer was found to follow the characteristic S-shape.
The phenomenological algorithm, being less computationally expensive, was found to be an effective predictor
to quantitatively assess peri-prosthetic tissue formation and evolutionary tissue stiffness as compared to cellphenotype
specific algorithm.
[1] Andreykiv et al., Biomech Model Mechanobiol,7,443–461.
[2] Isaksson et al., JTheor Biol,252,230–246.
[3] Claes and Heigele, JBiomech,32,255–266.
[4] Ghosh et al.,Proc Inst MechEng H,227, 490–502.

Stress shielding–induced bone resorption around cementless acetabular components has been indicated as a potential failure mechanism that may threaten long-term fixation. Using a bone remodelling algorithm in combination with three-dimensional finite element models of intact and implanted pelvises and musculoskeletal loading during normal walking, the objectives of the study were to investigate the deviations in load transfer due to implantation and bone adaptation around cementless metallic and ceramic acetabular components. Variations in implant–bone interfacial condition affected strain shielding and bone remodelling; strain shielding was higher for the bonded condition as compared to the debonded condition. For bonded interfacial condition, severe bone resorption, 20%–50% bone density reduction, was observed within the acetabulum. Considering debonded implant–bone interface, bone density increase of 50%–60% was observed around the supero-posterior part of acetabulum, whereas bone density reductions were low (2%–15%) in other locations. The implant–bone interface appeared less likely to fail, post-operatively and after bone remodelling. Moreover, the implant–bone micromotion was found to be low, less than 100 µm. Strain shielding and bone remodelling were almost similar for the metallic and ceramic components. Based on the results of this study, the ceramic acetabular component appeared to be a viable alternative to metal.