Faculty of Engineering,
University of Pisa (Italy)
Center of research “E.Piaggio”
BIOmimetic structures for
LOComotion in the Human body
Prof. Danilo De Rossi
Ing. Giovanni Vozzi
Dr. Michela Rosi
Ing. Luigi Gerovasi
Ing. Alberto Mazzoldi
Objective:
The aim of the project is to understand motion and perception
system of lower animal forms, such worms, insects and
snakes and eels, and to design and fabricate bio-inspired
mini- and micro-machines able to navigate in difficult
cavities, in particular in the human intestine.
To project a micro robot
To obtain this goal
To test mucoadhesive and Shape
memory Polymers
Our attention is focused on
earthworms, geckos and snails
To microfabricate short “legs” from shape memory polymers
To cover the SMP legs with mucoadhesive polymers
Shape Memory Polymers and Shape Memory Alloy
They both regain the memorized shape
(original shape) when heat is applied but
there is difference in that "alloy" is hardened
when heat is applied while "polymer" is hard
(like plastic) at low temperature but it is
softened (like rubber) when heat is applied.
"Polymer" can be changed in shape into any
direction to a desired degree, chemicalresistance, standing ability against repeated
deformations and ability to fit users' needs.
Fig 1. Shape-memory polymer converts from a temporary shape
(left) to its parent shape (right) in 45 seconds at 65 ºC.
A shape-memory polymer is a product, created by utilization of
the shape memorizing mechanism of elastomer of polyurethan
family, developed by Mitsubishi Heavy Industry.
The Shape Memory Polymers combine the advantages of
polyurethane with the characteristics of “smart material”
technology.
SMP changes mechanical properties from hard to soft
quickly when the temperature changes
SMP changes shape when heated and retains its new shape
when quickly cooled
Properties:
SMP undergoes transformation at biocompatible
temperatures in the range of normal body temperature
SMP is available in pellets or solution, and can be easily
compounded, formed by extrusion, injection molding,
coating or casting process in conventional manufacturing
environments
When ambient
temperature is
below the
activation point
The molecular structure is rigid
When ambient
temperature is
above the
activation point
Micro-Brownian movement creates
gaps between molecules
Characteristic of mucus
Mucus forms a continuous, insoluble adherent gel layer which
protects the underlying mucosa from the hostile environment of the
intestinal lumen.
The mucus consists of about 95-99% water and 5-1% glycoproteins,
plus a large number of other components such as electrolytes,
lipids, proteins and nucleic acids
The turnover time of the mucus gel layer appeared to be no longer
than approximately 1-4h, although this number is based on several
assumptions and was obtained from isolated rather than normal
gut segments.
The mucin protein core consists of
highly
glycosylated
regions (resistant
to proteolysis)
regions sparsely or
non-glycosylated
(susceptible to
proteolysis)
The polymeric structure is stabilized by interchain
disulphide bridges. There are approx. 150 disulphide bridges
and 53 free thiol groups per mucin polymer. The proteins are
particularly rich in proline and in hydrophobic amino acids.
Mechanism and theory of mucoadhesion
Many theories have been put forward to explain the mechanisms of
mucoadhesion, including electric theory, adsorption theory, diffusion
theory and wetting theory, although no theory alone can elucidate
this process.
Intimate contact of mucus and
polymer
Penetration into the mucus gel
Chemical binding
The electrostatic attraction is suggested to be able to facilitate the
intimate contact, while the presence of hydrophilic groups such as
OH, NH2 and COOH, sufficient polymer chain flexibility and
favourable polymer conformation are considered to be essential for
successful mucoadhesion.
Electronic
theory
Adsorption
theory
Wetting
theory
Diffusion
theory
Electronic theory: Bioadhesion in this case is due to an attraction
across the electrical double layer.
Adsorption theory suggests that bioadhesion is due to secondary
forces such hydrogen bonding.
Wetting theory uses interfacial tension to predict the degree of
spreading of a gel on the mucosa, which can than be used to predict
the degree of mucoadhesion
Diffusion theory: interpenetration of polymer chains are responsible
for mucoadhesion. It is believed that an interpenetration layer of 0,20,5 μm is required to produce an effective bond.
Materials and methods
Mucin type I (BSMG,) with 12% of sialic acid;
Mucins type II, with 1% of sialic acid;
Mucins type III (PSI) with 1% of sialic acid;
Many studies use three types of mucins, because different amount of sialic acid can
induce different characteristics of mucoadhesion
Polymers:Carbopol 974P, Carbopol 971P e Noveon AA-1
The mucin is prepared at 4%w/w, and the polymer at 0,25-1,5% w/w
by dispersing the required amount of polymer and mucin in ultra
pure water. The pH is adjusted to physiological pH (7.4) using 1 M
NaOH or TEA and the samples are then allowed to equilibrate at
4°C overnight.
Same polymers that present mucoadhesive
properties are:
Hydroxy propyl cellulose HPC
Poly vinyl pyrrolidone PVP
Hydroxy propyl methyl cellulose HPMC
Sodium carboxymethyl cellulose CMC
Poly vinyl alcohol PVA
Poly acrylic acid e Poly methacrylic acid PAA e PMA
Hyaluronic acid
Chitosan
Poly acrylic acid e PEG
Gelrite®
Carrageenan type I e II
Carbopol 971P® CP, 974P e Noveon AA-1
Carbopol polymers properties:
Carbopol polymers are high molecular weight, crosslinked, acrylic
acid-based polymers.
Carbopol homopolymers are polymers of acrylic
acid crosslinked with allyl sucrose or
allylpentaerythritol.
Carbopol copolymers are polymers of acrylic
acid, modified by long chain (C10-C30) alkyl
acrylates,
and
crosslinked
with
allylpentaerythritol.
Noveon's pharmaceutical resins are offered as
fluffy, white, dry powders.
Hydrogen bonding is a key part of the mechanism of the mucoadhesion
Carbopol contain a great number of carboxylic acid –COOH groups
pH value low, acidic
conditions
The polymer adheres better
at acidic pH levels , acid
groups are ionized less than
10%, so they form H-bonds
pH value high,
basic conditions
The polymer is ionized,
under more alkaline
conditions, the Carbopol
gels are very highly swollen,
and the chains are stiffened
by electrostatic repulsion of
the anionic charges along
the backbone.
Our idea is to build a micro robot, able to move autonomously,
and to unite this with legs of a Shape Memory Polymers
covered with mucoadhesive polymers.
Test the
temperature
dependent
properties of SMP
Build micro legs of SMP with
modulable mechanical resistance,
by varying the temperature, the
shape of polymer
Test the
mucoadhesive
properties of
Carbopol polymer
by test this polymer
by specific method
Vary the pH value and the
concentration of polymers, to test
the mucoadhesive properties
Testing device: functioning scheme
Sample trolley
Oscillatory plane
Brushless Motor
reduction
Testing device: detail of trolley
green deformable
sheet
blue strain gauge
To project a micro-robot
Two counter motors
An eccentric mass
Asymmetrical skates
Total weight 70g
Length 70mm
Second prototype:
dimensions  31/25 mm x 61 mm
Eccentric
rotors
CCD and LED bulb
Lithium
batteries