Faculty of Engineering, University of Pisa (Italy)

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Faculty of Engineering, University of Pisa
(Italy)
Center of research E.Piaggio
BIOmimetic structures for LOComotion in the Human
body
Prof. Danilo De Rossi Dr. Michela Rosi
Ing. Giovanni Vozzi Ing. Luigi Gerovasi Ing.
Alberto Mazzoldi
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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
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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
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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, chemical-resistance, standing ability
against repeated deformations and ability to fit
users' needs.
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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.
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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
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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
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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.
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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.
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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.
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Electronic theory
Wetting theory
Diffusion theory
Adsorption 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
0,2-0,5 µm is required to produce an effective
bond.
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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
PolymersCarbopol 974P, Carbopol 971P e Noveon
AA-1
The mucin is prepared at 4w/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 4C overnight.
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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
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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.
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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
pH value high, basic conditions
The polymer adheres better at acidic pH levels ,
acid groups are ionized less than 10, so they
form H-bonds
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.
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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 mucoadhesive properties of Carbopol
polymer by test this polymer by specific method
Test the temperature dependent properties of SMP
Build micro legs of SMP with modulable mechanical
resistance, by varying the temperature, the shape
of polymer
Vary the pH value and the concentration of
polymers, to test the mucoadhesive properties
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Testing device functioning scheme
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Testing device detail of trolley
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To project a micro-robot
Two counter motors An eccentric
mass Asymmetrical skates Total weight
70g Length 70mm
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Second prototype dimensions ? 31/25 mm x 61 mm
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