The Russian Eye and Plastic Surgery Centre's scientific results and their practical realization made it possible to develop the concept of regenerative surgery on the basis of the Alloplant transplantational technologies. Long-term experience of the experimental and clinical studies of the produced Alloplant biomaterials is a convincing proof of their selective effect upon the process of reparative regeneration of different tissues and anatomical structures. This exclusively promising line opens up opportunities for treatment of widely spread autoimmune, hereditary and vascular diseases. When using different types of the Alloplant biomaterials, it is possible to stimulate regeneration of sanguiferous and lymphatic vessels, cornea, sclera, integument, conjunctiva, nerves, parenchyma of liver, mucous coat of gastrointestinal tract, etc. Alloplant has been successfully used for the last two decades in the treatment of diabetic retinopathy, retinitis pigmentosa, optic nerve atrophy, uveitis, thromboses of the retinal veins, leucomas, traumata, keratites, myopia, tumours, burns and congenital defects.
Alloplant is widely used in ophthalmology, maxillofacial surgery, plastic surgery, stomatology, thoracal surgery, neurosurgery, proctology, orthopedics, traumatology, liver surgery, gynecology, etc. We have gained experience of using Alloplant biomaterials in different fields of pediatric surgery. Besides special transplants have been developed for reconstructive surgeries in children in case of maldevelopment of the digestive, respiratory, musculoskeletal systems. All the Centre's scientific, medical and productional structures are functioning as a unified complex in which the time between the development process of the new technology and its implementation is maximally shortened.
Production control
The Russian Federation Health Ministry approved the wide clinical application of the Alloplant graft biomaterial (Certificate # 901 of 22.07.1987)
Alloplant is included into the Russian General Classification of the biological products and allowed for the wide clinical application.
Specification # 42-2-537-93 (The Russian Federation Health Ministry; Registered # 056/003230 of 17.05.1993).
The harvesting of the donor cadaveric material is performed in accordance with the Russian Federation Law "About the transplantation of organs and tissues" # 4181-1 of 22.11.1992.
Before it goes into production the biomaterial undergoes the compulsory testing for AIDS (HIV), hepatitis B, hepatitis C, and syphilis. Besides these types of tests we use at different stages of the production the following additional types of control:
Morphologic
Biomechanical
Visual and microvisual
Optic polarization
Histochemical
Bacteriological
The developed technologies of the biomaterials processing and preservation and methods of their control guarantee sterility safety of their structure and plastic properties for the period of 5 years. The biomaterials should be stored at room temperature.
What is Alloplant biomaterial? (information for doctors)
It is well known that there are different allotransplantation
tissues : donor sclera, tendon, fascia lata, fat, skin, etc. But
there also exist some negative moments of tissue
allotransplantation, namely: immunological incompatibility of
tissues (K.Seifert, 1970; J. Bujia et al., 1991; A. Beigel et al., 1991), rejection (R. Klen, 1962; J. Tauro et al., 1991) and scarring around the allograft (A. Titova et al., 1979; M. Vrabel et al., 1993). This negative moments do not give the opportunity to use the tissue allografts widely in practice. For instance, the
reduction of the immunological incompatibility of tissues and
prevention of the allograft rejection require the application of
various immunosuppressive drugs, which are harmful for the
patient and can not give a reliable effect (R. Diasio, A. Lobuglio,
1996). The postoperative scarring following the allotransplantation
can cause different complications like the optic nerve
compression, formation of the drawn scar on the skin, deformation
of the eyelid, etc.
Our preliminary experimental investigations showed that
the tissue allotransplantation can not only provoke the immune
reaction, but also stimulate the regeneration of the recipient
tissues. Unfortunately, it is the regeneration of the scar that is
mainly stimulated, but sometimes the regeneration elements of
the natural reci pient tissues also take place.
In view of this, we supposed that under certain conditions
of tissue allotransplantation the growth of the natural tissues
may be achieved. We believed that the investigation of this
problem is of a paramount interest and importance, since it can open up new possibilities of surgery, connected with human
tissues regeneration.
Purpose of research
To reduce the antigenicity and stimulate the replacement of tissue allografts by natural reci pient tissues.
Material of investigations
Different tissues (tendon, fascia, skin, dura, fat, sclera, etc.)
from 105 human cadavers
Experimental allografting (rabbits — 176,
rats — 60, cats — 16) with postoperative
observations at 3, 5, 7, 14, 21,
30, 60, 90, 120, 180 and 360 days
Methods of investigations
anatomic
histologic
histochemical
electron microscopy
electron histochemical
immunologic
morphometry and photometry
Results in short
The investigations of the native (fresh) allograft tissues
(tendon, sclera, etc) showed that the prounounced immune
reaction (Fig. 1) is observed for 14-21 days postoperatively,
but later on the immune reaction is decreased with gradual
formation of the scar around the allograft.
What is the reason for the immune reaction decrease?
The electron histochemical studies revealed the extraction of
glycosaminoglycans from the collagen fibres (Fig. 2). It was
discovered that these glycosaminoglycans are situated between
the collagen fibres in the free state, whereas normally they are
located in the collagen fibres in the form of glycoproteins or
proteoglycans.
We assumed that free glycosaminoglycans can inhibit the
immune reaction. The cell culture studies revealed the inhibition
of lymphocytes migration under the influence of free
glycosaminoglycans.
Taking this fact into account, we can assume that the
investigations to elaborate the allografts with free
glycosaminoglycans can lead to the decrease of the allografts
antigenicity. But can the controllable extraction of
glycosaminoglycans from the collagen fibres be performed in
vitro?
The solution of this problem turned out to be very
complicated due to the necessity to stimulate some conditions
of the immune reaction in vitro. The controllable extraction of
glycosaminoglycans from the collagen fibres in vitro (Fig. 3)
was achieved only after three years of the scientific studies
using a specialy devised method of the cadaver tissues chemical
treatment.
The allografts with the controllable extraction of
glycosaminoglycans from the collagen fibres were named
ALLOPLANT. The testing of the Alloplant biomaterial showed
its low antigenicity and the ability to be well adopted in the
surgical wound.
Besides, there were defined the princi ples of the cadaver
tissues selection for allografting, based upon the revealed law
of approximately 70% structural resemblance between the graft
tissue and tissue to be restored.
The comparison of native allografts and the Alloplant
biomaterials has been done on the models of tendon, donor
sclera, fascia lata, viscleral fascia, dermal layer of skin and fat
tissue. In this review we draw attention only to the donor sclera investigations, carried out on 54 rabbits, which were operated on (experimental scleral reinforcement) using the native donor
sclera of rabbit (control group) and the Alloplant biomaterial,
prepared from the rabbit donor sclera (investigated group).
The comparative immunological investigations by Sewell (Fig.
4 and 5) showed that the density of the immunoactive cells
(lymphocytes, neutrophils), as well as edema and necrosis are
much more in case of the native donor sclera allografts (control
group), than in case of the Alloplant biomaterial (investigated
group).
The comparison of the humoral response and the
lymphocytes sensitation to saline extracts of sclera also showed a
slight antigenicity of the Alloplant biomaterial, whereas allografts
of native donor sclera were causing a marked immune reaction.
The comparative histological investigations in the early
period following the allotransplantation (3, 5, 7,14, 21 days)
revealed a rather severe inflammatory reaction (lymphocytes
and neutrophiles infiltration, edema) in case of the native donor
sclera allografting, whereas the Alloplant biomaterial led to the
low macrophagal and fibroblastic infiltration with slight edema
(Fig. 6, 7).
In the period of 21 and 30 days there started a process of
the allografts replacement by the recipient tissue in the form of
the proliferating fibroblasts introduction into the transplanted
tissue. Such process is similar for both types of the compared
allografts.
But later on (60, 90, 120, 180 days) the princi pal
differences of the allograft replacement in the control and
investigated groups have been discovered. The replacement of
the native donor sclera allograft (Fig. 8) leads to the formation
of the scarred capsule around the allograft due to the stimulation
of the scar tissue growth. The replacement of the Alloplant
biomaterial (Fig. 9) is accompanied by its gradual resorption
with the ingrowth of the native newly formed connective tissue
fascicles and gradual formation of the sclera-like tissue in the
place of the Alloplant without the formation of the scar-capsule.
Hence, the dense adhering to the reci pient rabbit sclera
has been revealed, whereas the scarring allograft of the native
donor sclera was detached from the recipient rabbit sclera and
deformed.
In 360 days there were observed a severe scarring of the of
the native donor sclera allograft, its significant detachment from
the reci pient rabbit sclera and deformation (Fig. 10). During the same period the Alloplant biomaterial was fully replaced by the natural sclera-like tissue with no signs of scarring. The Alloplant
biomaterial and the reci pient rabbit sclera looked like one thick
sclera (Fig. 11).
Therefore, as compared to the native donor sclera
allografts, the Alloplant biomaterial after the experimental scleral
reinforcement surgery causes a slight immune reaction and is
gradually replaced by the natural reci pient sclera-like tissue
without scarring.
The similar results were also achieved when the Alloplant
biomaterial and native allografts were compared on the models
of tendon, fascia lata, viscleral fascia, dermal layer of skin and
fat allotransplantation. It became clear that the Alloplant
biomaterial (that is specially selected allografts with controllable
extraction of glycosaminoglycans from the collagen fibres) can
be replaced by different types of native reci pient tissues without scarring.
What types of natural reci pient tissues can replace the
Alloplant biomaterial? The investigations showed that the
peculiarities of the regenerate depend on the properties of the
Alloplant biomaterial. This dependence turned out to be very
complicated, but we considered mainly the dependence on the
glycosaminoglycans content in the Alloplant biomaterial. For
the discovery and calculation of glycosaminoglycans we used
the photometric method by special staining (Fig. 12). The studies regarding this aspect revealed the following.
If the Alloplant biomaterial has a high content of the
hialuranic acid, then it will be mainly replaced by the dense
connective tissue (Fig. 13). This regenerated dense connective
tissue can be appropriate for the repair of such anatomic
structures as a tarsus of the eyelid, a periostarm, a part of bone, etc.
If the Alloplant biomaterial has a low content of the
hialuranic acid, then it will be mainly replaced by the loose
connective tissue (Fig. 14). This regenerated loose connective
tissue can be suitable for the surgical restoration of the fat
tissue (contour plasty of the face, replacement of the orbital
fat, etc).
If the Alloplant biomaterial has a high content of
heparansulfate, the surface of such Alloplant will be excessively
epithelized (Fig. 15). This phenomenon gives a new opportunity
to restore the epithelium of conjunctiva, skin, etc.
If the Alloplant biomaterial has a high content of
keratansulfate, then the Alloplant will be replaced (Fig. 16) by the typical corneal plates (transparent corneal tissue) as in the case of lamellar keratoplasty. The opportunity to restore its own
transparent corneal tissue with the use of a special Alloplant
biomaterial can open new ways for the treatment of cornea
diseases.
If the Alloplant biomaterial has a high content of
chondriotinsulfate, then the Alloplant will be replaced by vessels-
rich loose tissue (Fig. 17). The ability of special Alloplants to stimulate the blood vessels growth can be very important for various aspects of retinal surgery, cardiosurgery, etc.
Taking the above mentioned abilities of different Alloplant
biomaterials for selectible stimulation of the regeneration of
different types of natural reci pient tissues into account there
were developed the compound Alloplants which allow to form
rather complicated anatomical structures by way of the natural
growth of various tissues (face plasty, eyeball repair, etc).
Among other types there were also developed the Alloplant
biomaterials having diverse combinations of glycosaminoglycans
in it, which could stimulate the regeneration of other types of
tissues.
We devised a special powder-type Alloplant to stimulate the
regeneration of the hepatocytes, which gave very encouraging
clinical results in the treatment of the liver cirrhosis by the
Alloplant suspension injection into the liver. This powder
Alloplant is also used for the stomach ulcer healing
(gastrofibroscopic injection).
A special Alloplant biomaterial for osseous tissue growth
stimulation was tested for maxillofacial plasty and those tests
also showed the encouraging clinical results.
A special sponge-type Alloplant was developed, which allows
to absorb the intraocular liquid and is already being used for
the trabecular structure repair in glaucoma.
At present princi pal elaborations of the special liquid
Alloplant are being completed for the vitreous body replacement,
etc.
Thus, the Alloplant biomaterials cause a slight immune
reaction after the implantation and is gradually replaced by the
natural reci pient tissue without scarring. Different kinds of the
Alloplant biomaterials can stimulate the regeneration of different
tissues.
Discussion
The stimulation of the reci pient tissues regeneration by
tissues allotransplantation is well known (M. Bert, R Maarlyn,
1978; R. Nigmatullin, 1996; etc.).
But what is always growing is the scar, which can not
perform the function of the natural tissues. The scar figuratively
plays the role of the patch in the tissues, closing the defect.
Moreover, the scar has the property to be compressed, that™s
why the scarring can give a number of postoperative
complications like the compression of the optic nerve, scar
deformation, etc.
The phenomenon of the property allografts with controlable
extraction of glycosaminoglycans from collagen fibres to stimulate
not the scar regeneration, but the regeneration of normal native
reci pient tissues was discovered for the first time. We found
that this feature is common for different kinds of allografts
(tendon, donor sclera, fascia, etc.), where the controllable
extraction of glycosaminoglycans from collagen fibres was done.
A special selection of such allografts for surgeries according to 70% structural resemblance with tissue to be restored allowedin addition to prevent scarring. The selection of the allografts with the controllable extraction of glycosaminoglycans according
to the content of glycosaminoglycans in it allowed to selectively
stimulate the regeneration of different types of natural reci pient
tissues.
Allografts with the mentioned properties were named Alloplant biomaterial.
The main peculiarity of the Alloplant biomaterial is the
stimulation of the normal natural recipient tissues during the
resorption and replacement of the Alloplant. As a result of the long term scientific investigations there were developed many
kinds of Alloplant biomaterials, which can stimulate the regeneration of different types of natural reci pient tissues: blood vessels, lymphatic vessels, tarsus, sclera, periosteum, osseous,
fat tissue, epithelium, cornea, conjunctiva, etc.
On the basis of this, it is reasonable that the Alloplant
surgery can be one of the aspects of the regenerative surgery,
that is the surgery directed to the stimulation of normal natural
human tissues growth.
At present there are produced many kinds of the Alloplant
biomaterials, which are used in clinical practice of Russia.
Alloplant biomaterials opened up possibilities to treat those
patients who are considered to be incurable (retinitis pigmentosa,
phthisis bulbi, etc).
In this review we draw your attention to several aspects of
the Alloplant biomaterial usage in clinical practice.
