PROJECT ON BONE INGROWTH AND
COVERAGEME 6505 - Engineering Materials in Medicine
Presented byGroup III
TEAM MEMBERS
Aravind Baskar
Cao Jiawei
Debirupa Mitra
Karthik Mamandur
Gopalakrishna
Lew Maan Tarng
Naresh Kumar Thanigaivel
Steffie Mano
Tekumalla Venkata Rama
Lakshmi Sravya
Wang Jiahui
Wang Yuzhe
OUTLINE
Introduction
Need for bone implants
Commercial implant materials
Surgical procedure of implants
Project
Measuring techniques and grids
Core project results explanation
Results and discussion
Mechanism of bone integration
Bone remodelling
Bone coverage with time
Others computation methods
PRESENT TO FUTURE
NEED FOR BONE IMPLANTS
Customer Needs
Aging population; expanding pool of
younger patients (minimally invasive
procedures)
Autograft, allograft, bone substitutes
Substitutes introduced due to quantity
limitation and chronic pain of the donor site
More desirable due to less operation time
Company Needs
Increasing customers
Shift to more expensive
demineralized bone matrix
$2.5 billion market, ↑
COMMERCIALLY AVAILABLE IMPLANTSPRODUCT COMPANY COMPOSITION USE PROPERTIES
ProOsteon® 200R
BiometThin coralline-derived HA layer on Calcium carbonate matrix Bone void filler
BioresorbableOsteoconductive
ChronOsTM DePuySynthes
Pure β-TCP
MasterGraft® Putty
MedtronicBiphasic Calcium Phosphate (15% HA, 85% β-TCP) & Type 1 bovine Collagen
Bone void filler/graft extender
Vitoss® BA Stryker70% β-TCP, 20% collagen, 10% bioactive glass
Bone void filler
Actifuse® ABX BaxterSilicon (0.8% by weight) substituted calcium phosphate
BioresorbableOsteoconductive
SURGICAL PROCEDURE OF IMPLANTS
SuturingInsertionHole on animal part
• E.g. Femoral Condye with 4mm diameter and 7mm depth
Sterilization of Bone implant material
• @ 150°C for 4hrs
Animal
• E.g. Rabbit
SURGICAL PROCEDURE OF IMPLANTS
Ref: [1] Patel, N., Best, S. M., Bonfield, W., Gibson, I. R., Hing, K. A., Damien, E., & Revell, P. A. (2002). A comparative study on the in vivo behavior of hydroxyapatite and silicon substituted hydroxyapatite granules. Journal of Materials Science: Materials in Medicine, 13(12), 1199-1206.
HISTOLOGYHistology is an essential tool of biology and medicine. The study of tissues and organs through the
examination of the microscopical architecture of tissues and the relationship between the
different types of cells and tissue types found within tissues and organs.
Receipt and Identification
Labelling of Specimen
Fixation
Dehydration
Clearing
Impregnation
Embedding
Section Cutting
Staining
Mounting
Protocols in Histotechniques:
Stereology Grids
It Provide an established set of tools for the stereological estimation of bone perimeter, bone area, and bone surface.
Available Grids
Merz Grids: Bone Perimeter and Area Estimation
Point Grid: Quick Bone Area Estimation
XY Lines Grid: Systematic Random Sampling
Weibel Grids: Bone Perimeter and Area Estimation
Cycloid Grids: Bone Surface Estimation
How and Why do they do it?
The grids are super-imposed onthe images of the slides todetermine the quantitativeparameters of tissue structureon sections.
It includes the estimation ofvolumetric ratios, surface areas,surface-to-volume ratios,thicknesses of tissue or cellsheets and the number ofstructures.
HISTOLOGY
MEASUREMENT TECHNIQUES AND GRIDS
Ref. : Weibel & Elias, 1967; Weibel, E. R., Kistler, G. S., & Scherle, W. F. (1966).
MEASUREMENT TECHNIQUES AND GRIDS
Method of estimating
surface area:
Method of estimating volumetric
composition of tissues:
Method of estimating surface to
volume ratio:
Ref. : Weibel & Elias, 1967; Weibel, E. R., Kistler, G. S., & Scherle, W. F. (1966).
SOLUTION METHODOLOGY
The given micrographs were studied according to the
techniques mentioned in the project description and the
results were analysed and compared with the literature / ref.
materials. From the results and the literature review the final
solutions were arrived.
COMPUTATION METHOD
MICROGRAPH - I
Measurement of Bone Ingrowth
Zone HBI AZBI Avg.
I 6 14%
21%II 8 19%
III 14 33%
IV 8 19%
MICROGRAPH - II
Measurement of Bone Ingrowth
Zone HBI AZBI Avg.
I 8 19%
32%II 9 21%
III 16 38%
IV 20 48%
MICROGRAPH - III
Measurement of Bone Coverage
Zone HBC HIS ZBC Avg.
I 10 29 26%
52%II 23 14 62%
III 19 11 63%
IV 22 13 63%
MICROGRAPH - IV
Measurement of Bone Coverage
Zone HBC HIS ZBC Avg.
I 24 3 89%
83%II 16 1 94%
III 10 6 63%
IV 26 6 81%
RESULTS & DISCUSSION
Parameter Micrographs – I & III Micrograph – II & IV Therefore, over time, a
Si-HA implant will have
significantly enhanced
bonding with the human
system than a HA
implant.
Bone Ingrowth 21% 32%
Bone Coverage 52% 83%
From the data, it is inferred that micrographs I & III
belong to HA and micrographs II & IV belong to Si-HA
as a result of better bone ingrowth and coverage.
REASONS FOR INCREASED BONE INGROWTH IN SI-HA IMPLANTS
FORCE VIEW
Incorporation of Si into the HA lattice results in an increased Van der Waal’s
interaction and an increase in the negative surface charge density in comparison
to the unsubstituted HA.
Average adhesion force versus surface charge for HA and Si-HA surfaces
Ref: J. Vandiver, D. Dean, N. Patel, C. Botelho, S. Best, J. D. Santos, M. A. Lopes, W. Bonfield, and C. Ortiz, “Silicon addition to hydroxyapatite increases nanoscale electrostatic, van der Waals, and adhesive interactions.,” J. Biomed. Mater. Res. A, vol. 78, no. 2, pp. 352–63, Aug. 2006.
REASONS FOR INCREASED BONE INGROWTH IN SI-HA IMPLANTS
Day 1 Day 3 Day 42
Coating morphology on Day 1, Day 3 and Day 42.
Ref: E. S. Thian, J. Huang, S. M. Best, Z. H. Barber, R. A. Brooks, N. Rushton, and W. Bonfield, “The response of osteoblasts to nanocrystalline silicon-substituted hydroxyapatite thin films.,” Biomaterials, vol. 27, no. 13, pp. 2692–8, May 2006.
MATERIALS VIEW
Silicon causes the tetrahedral distortion and disorder at the hydroxyl site
which decreases stability of the apatite structure and increases the bio reactivity
by forming a carbonate containing apatite layer which favours cell adhesion.
REASONS FOR INCREASED BONE INGROWTH IN SI-HA IMPLANTS
Water spreading behavior on the surface of Si-HA coatings
Contact angle measurements of HA and Si-HA surfaces
Ref: J. Vandiver, D. Dean, N. Patel, C. Botelho, S. Best, J. D. Santos, M. A. Lopes, W. Bonfield, and C. Ortiz, “Silicon addition to hydroxyapatite increases nanoscale electrostatic, van der Waals, and adhesive interactions.,” J. Biomed. Mater. Res. A, vol. 78, no. 2, pp. 352–63, Aug. 2006.M. A. Surmeneva, A. Kovtun, A. Peetsch, S. N. Goroja, A. A. Sharonova, V. F. Pichugin, I. Y. Grubova, A. A. Ivanova, A. D. Teresov, N. N. Koval, V. Buck, A. Wittmar, M. Ulbricht, O. Prymak, M. Epple, and R. A. Surmenev, “Preparation of a silicate-containing hydroxyapatite-based coating by magnetron sputtering: structure and osteoblast-like MG63 cells in vitro study,” RSC Adv., vol. 3, no. 28, p. 11240, Jun. 2013.
SURFACE VIEW
Si-HA has a lower contact angle and is more hydrophilic than HA.
BONE COVERAGE CHANGE WITH TIME
Ref: Patel N, Brooks RA, Clarke MT, Lee PMT, Rushton N, Gibson IR, et al. In vivo assessment of hydroxyapatite and silicate-substituted hydroxyapatite granules using an ovine defect model. J Mater Sci. 2005;16: 429-40
MECHANISM OF BONE INTEGRATION Implanted granules dissolve to release Ca2+ and
PO43- ions into the ECM
Cell signaling is triggered due to formation ofapatite-like surface layer
Proteins will deposit onto implant surface.
Following initial protein adsorption, cellrecruitment is stimulated over the implantsurface
Cells adhere over implant surface
Cells proliferate and differentiate, accompaniedby the mineralization of calcium phosphate
Interlock bonding between existing bone andimplant material
Consequently implanted region is filled upsuccessfully leading to bone integration
BONE REMODELLING
Ref: A presentation on “ Bone Histology and Histopathology for Clinicians “by Stephen F. Hodgson.
ADDITIONAL COMPUTATIONAL METHOD
Image processing using MATLAB
For measurement of bone ingrowth
Turn original image to gray image
Find the two threshold values by
‘multi-thresh’ function
Label the 3 groups determined by the threshold values
Find the number of pixels which belong
to the new bone
Calculate the
percentage of bone
ingrowth
ADDITIONAL COMPUTATIONAL METHOD
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