REPORT ON THE USE OF COLLAGEN AS A BIOMATERIAL

Collagen is a highly versatile material that is extensively used in the medical, dental
and pharmacological fields. Collagen is capable of being prepared into cross-linked
compacted solids or into lattice-like gels. Miyata, T. Taira et.al (1992).Use of
collagen in the form of tendons as suture material goes back to millennia and can hold
its ground with catgut, which is still representing a useful suture material in surgery.
Cen, W. Liu, L. Cui, W. Zhang et.al (2008)
The main applications of collagen are for burn/wound cover dressings, osteogenic and
bone filling materials, antithrombogenic surfaces and immobilization of therapeutic
enzymes. Recently, use of collagen as a carrier for drug delivery has attracted many
researchers throughout the world. Collagen-based drug delivery systems include
injectable microspheres based on gelatin (degraded form of collagen), implantable
collagen–synthetic polymer hydro gels, interpenetrating networks of collagen and
synthetic polymer collagen membranes for ophthalmic delivery. Remi, G. Robert and
B. François (2010)
Resorbable forms of collagen have been used to dress oral wounds, for closure of
graft and extraction sites and to promote healing. Collagen-based membranes have
also been used in periodontal and implant therapy as barriers to prevent epithelial
migration and allow cells with regenerative capacity to repopulate the defect area. It
has been hypothesized that membrane regenerative techniques facilitate the natural
biological potential by creating a favorable environment for periodontal and
peri-implant regeneration. Miyata, T. Taira et.al (1992)
Collagen is used as a membrane due to the following reasons: It is the major
extracellular macromolecule of the periodontal connective tissue and is
physiologically metabolized by these tissues, it is chemotactic for fibroblasts, it has
been reported to act as a barrier for migrating epithelial cells in vitro and it is a weak
immunogen that has been used experimentally in animals and humans. Pitaru et al. in
a series of experiments concluded that type I collagen has the capacity to support
regeneration of periodontal tissues. Kanagaraj, K.C. Velappan, N.K et.al (2006)
STRUCTURE OF COLLAGEN
Astbury was the first to suggest a structure for collagen in 1938, which consisted of a
mixture of Trans and Cis peptide units, and the same feature was incorporated by
Pauling and Corey in the model proposed by them in 1951 that had three co-axial
helices. However, neither of these structures was in agreement with the observed
X-ray diffraction pattern of collagen fibers. It was Ramachandran's group from
Madras, India, who first postulated a triple helical structure for collagen. M. Pavel, L.
Ferdinand, et.al (2009)
The collagen molecule consists of three polypeptide chains twined around one another
as in a three-stranded rope. Each chain has an individual twist in the opposite
direction. The principal feature that affects a helix formation is a high content of
glycine and amino acid residues. The strands are held together primarily by hydrogen
bonds between adjacent CO and NH groups and also by covalent bonds. The basic
collagen molecule is rod shaped with a length and a width of about 3000 and 15 A,
respectively, and has an approximate molecular weight of 300 kDa. The triple helix
structure contains three basic amino acids: Glycine, proline and hydroxyproline. The
pattern is glycine, proline and X, with X being any amino acid. Specific amino acids
cause specific functions for the collagen. Hydrogen bonds hold the helix structure
together by linking peptide bonds. L. Cen, W. Liu, L. Cui, et.al (2008)
The individual triple helices or tropocollagen molecules, as they are sometimes called,
are arranged to form fibrils that are of high tensile strength and flexibility and can be
further assembled and cross-linked so as to support stress efficiently. Abnormalities in
the collagen molecular structure or its organization into mature fibers leads to
different diseases associated with connective tissues, such as Ehlers-Danlos syndrome,
osteogenesis imperfecta and some types of osteoporosis and arthritis. M. Pavel, L.
Ferdinand, et.al (2009)Fig. 1. (a) Schematic diagram of triple helical structure of
collagen and (b) SEM image of isolated collagen from CCLW.

2.0 DIFFERENT TYPES OF COLLAGENS AND ITS APPLICATION

Collagen based biomaterials are widely used as scaffolds for bone formation, tissue
substitutes, gene delivery and as biomarkers in osteoarthritis. Various types of
collagen, their tissue distribution and functions are given below in Source: P.B. Remi,
G. Robert and B. Franço (2010)2.1.
3.0 APPLICATIONS OF COLLAGEN
Collagen, a versatile biomaterial finds its application in various fields and has its wide
applicability in the following:
(a) Tissue engineering application
A wide variety of substances such as metals (tita-nium), ceramics (alumina), synthetic
polymers (poly-urethanes, silicones, polyglycolic acid (PGA),polylactic acid (PLA),
copolymers of lactic and gly-colic acids (PLGA), polyanhydrides (polyorthoesters)
and natural polymers (chitosan,glycosaminoglycans, collagen) are used in the
pro-duction of biomaterials for biomedical applications. Among these substances
collagen-based biomaterials find their potential application in tissue engineering
because it is distinct from other synthetic polymers. Generally biomaterials such as
collagen enhance repair of tissues such as bone,tendon, ligament, skin, vascular and
connective tissues. Due to the coherency with the biological property with that of
native collagen that already exists in our body system it may also function as cell
scaffold for tissue engineering applications.
This biocompatibility with the native collagen has provoked its potential role in tissue
engineering and in the design of biomaterials which can regulate and define most of
the tissues which depend on the collagen based biomaterials. The applicability of it in
tissue engineering applications has an intensive growth for the past new decades P.B.
Remi, G. Robert et.al (2010).
The fabrication of dense and porous collagen membranes for wound dressing and
tissue engineering were carried out using techniques such as air-drying and
freeze-drying. The use of collagen and fibrin in hydrogel scaffolds plays an important
role in promoting cell differentiation on adipose derived stem cells (ASC’s). P.
Hyoungshin, K. Sandeep, et.al (2010)
(b) Synthesis of biomimetic hydroxyapatite (HA) nanoparticles
The problems associated with the synthesis of biomimetic monodisperse particles
with uniform morphology and narrow size distribution for HA synthesis prevails as a
challenge for the scientists working on materials and this may be overcome using
nanoparticle synthesis. Collagen omposite scaffolds formed by 70 wt.% HA particles
dispersed in it provide a chemical environment characteristic of bone and are intended
for tissue engineering applications.Though bio mimetic HA is prepared usingdifferent
technologies the synthetic HA prepared using direct nucleation technique mimicked
the natural bone. T. Anna, C. Giancarlo et.al (2003)
(c) Collagen-fibroin/ HA
Composite prepared using a combination of Type I collagen and silk fibrin were used
to fabricate bio mimetic bone substitute materials. Certain studies have proved the
safety and potential clinical benefit of Type I collagen used to prepare HA
nanoparticles apart from its bio-mimetic property.
Such bio-material prepared using the Type I collagen as a scaffold is used to
regenerate cartilage and subchondral bone. Though collagen based porous HA
bio-material is widely used as a scaffold for bone tissue engineering its use is limited
due to its high cost and low initial strength. This problem can be overcome by using
porous 3D collagen and incorporating nanosized HA particles. Z. Hongshi, W.
Guancong, et.al (2011)
(d) As bone substitutes
HA powder coated with collagen is used as an inject-able bone substitute.
Platelet-derived growth factor-BB when incorporated into an organic bovine
bone-collagen matrix stimulates osteoblastic cell proliferation and also acts as a
mineral-collagen bone substitute (MCBS). MCBS when combined with recombinant
human platelet-derived growth factor-BB also finds its application in soft tissue
healing such as buccal wall extraction defects. M.L. Nevins, M. Camelo, P.
Schupbach, D.M. Kim, J.M. Camelo and M. Nevins(2009).
SiO2-based calcium phosphate - collagen is used as a bio-compatible bio-material
bone substitute granules to assist rapid vascularization and to promote cell growth .
Collagen and HA composites incorporated with growth factors helps in repairing hard
tissues such as bones . Bone composite materials containing collagen/chitosan
micro-granules were prepared and found to have high bone forming efficacy. This
property may be due to the interconnected pores formed between the micro-granules
which in-turn allowed new bone in growth and vascularisation. Y.L. Jue, H.K.
Kyoung, et.al (2006)
(e) Ophthalmic applications
The newer ophthalmic forms such as polymeric gels, colloidal systems, cyclodextrins
and collagen shields provide an improved ocular drug bio-availability when compared
to the conventional dosage. This increases the drug availability, retentivity,
sustainability, penetrability
and solubility at the site of action. Apart from this, the advanced formulation differs
from conventional dosage in many aspects such as applicability, acceptability and
utility which can be easily understood. Arul Kumaran, K. Karthika et.al (2010)
So, the recent developments in ophthalmic research will pay much attention to
develop a non- invasive sustained drug release and as a promising approach with an
improved ophthalmic therapy for the treatment of vision-threatening disorders. An
improved ophthalmic method of treatment remains as a good platform for the
treatment of eye disorders. Due to the improvement in property of drug delivery
systems. K.S. Rathore and R.K. Nema (2009)
(f) Ophthalmic formulations
Ophthalmic formulations can be broadly categorized into two major forms which
include ophthalmic drug inserts and advanced drug delivery formulations. The
ophthalmic drug inserts includes formulations such as soluble ocular drug insert
(SODI), bioadhesive ophthalmic drug inserts (BODI), ocusert or ocular films, eye
implants, insitu gel, collagen shields and ocufit. The advanced drug delivery
formulations broadly include formulations such as nanosuspension, nanoparticles,
liposome, niosomes, iontophorosis, minidisc and new ophthalmic delivery system
(NODS). Both types of formulations show a high potential application when
compared to the previously existing dosage forms.
Among these formulations collagen finds its application mainly in preparation of
collagen shields for ophthalmic application and in other formulations it is being used
as an additional substance due to its bio-compatibility and easy availability . K.S.
Rathore and R.K. Nema (2009)
(g) Collagen shields
Collagen shields prepared using scleral collagen obtained from porcine or bovine
possess biodegradability and cross-linking property which improves the dissolving
capacity of shieldwhen placed under the eye for a maximum period of 72 hrs. Apart
from this, it extends its biomedical utility as drug delivery vehicle and as a protective
and lubricating agent.
Collagen shields when placed under the eye accelerate epithelialisation of the
ophthalmic membrane and this property makes them particularly to be useful in
ophthalmic surgical procedures. It also serves as a valuable therapeutic tool since it is
useful to deliver medications such as antiviral, anti-fugal, and immunosuppressive
agents. Keratomycosis is a type of fungal infection which is developed after cataract
surgery and this can be prevented at its early stage of infection by using collagen
shields which has been already soaked in an anti-fungal agent such as amphotericin
before application in the eye for the post operative infections. M. Javier, A. Jaime,
et.al (2000)
Scleral collagen obtained from porcine or bovine is also available as a corneal
bandage lens for the application as protecting agent in surgery and in traumatic and
non-traumatic corneal conditions. It acts as an efficient preparation for eye infections
when it is pre-soaked in a pharmacological agent. Pre-soaked collagen shields used
for drug delivery applications are also available with varying dissolution times of 12,
24, and 72 hours. Similarly, pre-soaked collagen shields prepared with water- soluble
antibiotic or in steroid solution are used for delivering and sustaining higher levels of
ocular activity in the targeted site to produce a higher therapeutic activity. Recently, a
study has proved that a major reduction in corneal ulcer is being obtained when a
collagen shield is placed bilaterally in the cornea of a pet rabbit. Y. Greenwald and G.
Kleinmann (2008)
(h) Eye implants
Eye implant is a form of sub retinal drug delivery system that has been developed in
order to over- come the limitations of current treatments for retinal diseases . The eye
implant also plays a vital role in treating diseases such as glaucoma and other
vitro-retinal disorders.Apart from this, the implants are synthesized based on the
electronic principle. One of such implant synthesized is micro-electromechanical
implant which is used to stimulate the retinal structures so that the lost in vision may
be restored with the stimulatory function of retinal membranes. Similarly a chronic
microelectronic retinal prosthesis is synthesized and implanted permanently in the eye
of the blind in connection with electronic components and digital camera in order to
detect the light, movement and recognition of shapes . Generally bio-compatible and
biodegradable eye implants are preferred for the treatment of ophthalmic disorders.
Such type of collagen based implant preparation has shown considerable applicability
because; it provides stable and reasonable control over the post-operative
complications such as intraocular pressure. Preparation of collagen based matrices
finds their use as corneal transplant and as temporary patches to repair perforations in
case of emergency situations. Y. Liu, L. Gan, D.J. et.al (2006)
CONCLUSION
In conclusion, collagen, a biological macromolecule can be isolated using simple
methods from the biological connective tissue wastes. The isolated collagen from
different sources finds its versatile role in pharmaceutical and biomedical applications.
Collagen finds its potential applications in fields such as ophthalmic, orthopaedics,
burn/wound management and tissue engineering applications.Apart from this it plays
a major role in delivering therapeutic substances such as drugs, proteins and genes at
the targeted site. Thus, this review highlights the benefits of collagen in various
biomedical fields and its isolation from bio wastes which helps in reducing the
environmental pollution.

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