1.

Diversity of Collagen in biomaterial (protein in bone

and connective tissues)

Collagen is a naturally occurring matrix polymer which is highly conserved across species. It
is the predominant extra-cellular matrix component of most connective tissues within the
mammalian body, comprising one third of all protein found within tissues. Collagens are
extracellular and have a mainly structural role. Critical parameters including density, packing
and orientation (or direction) results in distinctively varying mechanical properties in tissues
such as bone, skin, tendon and cartilage.

In connective tissue lost to trauma or disease, replacement tissue strategies, have to consider
mechanical implications. Synthetic polymers can be designed to have the mechanical integrity
of the native structure to be replaced but eventually this will be degraded and replaced by the
host. The major target protein that will be replaced in connective tissues is collagen. The other
alternative is to start with collagen as a natural polymer substrate and tailor its mechanical
properties in vitro. Given the critical role this protein plays in tissue structure there have been
and continue to be efforts into extracting this protein, reforming 3D scaffolds for tissue
engineering as well as controlling density and direction parameters to form tissues in vitro. The
main difference in the building of bulk tissues is the cell-rich or matrix-rich nature of the tissue
being engineered. Where the matrix dominates a tissue, the mechanical properties of the matrix
are critical, i.e in connective tissue. In tendon for example, the alignment of collagen fibrils
along the principle axis of strain application, and the nature of a ‘dual’ size of fibril diameters,
provides incredible strength to this tissue. Compared directly to a tissue like dermis, where
collagen is interlocked in a basket-weave formation with elastin to provide tensile strength in
multiple axis to ensure stretching of this tissue does not compromise its integrity. Thus, when
engineering tissues in vitro, technologies and processing to control parameters of collagen
architecture have been developed to mimic those found in tissues in situ. This field of controlled
processing is growing, as the sophistication of methods employed to create biomimetic
scaffolds advances.

Type I collagen scaffolds are widely used in clinical practice and the collagen for these
materials are generally obtained either from cultured cells or extracted from native tissues.
Extraction encompasses the entire range from decellularisation of collageneous tissues
preserving the native architecture to the complete break down into collagen molecules which
can later be reconstituted into their native fibrillar structure. One of the most common collagen
scaffolds in clinical use is de-cellularised dermal tissue. By decellularising an entire piece of
connective tissue, the immunogenicity of the tissue is removed whilst retaining the collagen
architecture and other matrix components in the native form. These scaffolds induce and guide
tissue repair when implanted in a full-thickness skin defect as a template for dermal
regeneration. Methods to enhance the in vivo persistence of such decellurarised scaffolds,
involve dispersion of the collagen matrix. The dispersion of collagen can result in the
degradation of the collagen into polymers, oligomers or monomers dependent upon the
treatment methods applied. This is followed by co-precipition with a glycosaminoglycan. In
these cases the inherent architecture of the native tissue is lost and reformed in vitro.

The formation of living collagenous tissue equivalents rely upon the cell seeding of
decellularised native tissues or cell-seeding into prefabricated, porous collagen scaffolds. The
next generation of skin equivalents are bio-engineered cell based technologies using cell
produced collagen. These include the next generation bilayered skin equivalents produced by
Organogenesis. The use of solubilised collagen as dermal and lip fillers for the correction of
contour deformaties, is a growing cosmetic procedure. This relies upon collagen dispersion
from either human cadaver or bovine tissue, which can then be stably re-injected to ‘plump’ to
fill minor defects. The question is whether the fibrosis response by the injection of these
products causes the therapeutic effect or the products themselves.

The main focus of this chapter is to address the importance of collagen protein structure and
its relation to normal mechanical function in matrix-rich tissues. This chapter will overview
the established, clinically used and new novel processing technologies being researched to
improve and control bulk collagen processing for applications in regenerative medicine, and
new directions needed to control collagen architecture.

2. Biomaterials and nano- biomaterial used for medical

applications
Biomaterials are biocompatible,non toxic, non carcinogenic,non immunogenic and non
tetratogenic synthetic substance with adequate physical and mechanical properties used widely
in medical applications to augment or replace a natural body function(therapeutic uses)that can
be implanted or partially implanted or used as totally external devices. Medical applications
include drug delivery,clinical therapies, regenerative medicines,tissue engineering,implantable
devices.
Biomaterials in Drug Delivery
Drug delivery decribes the formulations or technologies of transfering or administering a drug
or pharmaceutical product in desired amount inside the body to achieve the desired therapeutic
effect.It should be safe and reliable with proper dosage.Drug release is from diffusion,
degradation, swelling, and affinity-based mechanisms. The rapid growth of nanoscale materials
led the existance of injectable targeted drug delivery systems in the form of inserts
(vaginal,ophthalmic), implants (intramuscular),topical(skin patches), surface coated (oral
tablets),injected nanocarrier ( polymer-drug conjugates) etc.
Bioelectrodes and Biosensors
Bioelectrodes are sensors used to transmit information into or out of the bodyand are mainly
applied in cardiology and neurology applications. Surface or transcutaneous electrodes used to
monitor or measure electrical events in the body. A biosensor uses biological molecules,
tissues, organisms to measure chemical or biochemical concentrations. Biosensors can be used
in many medical and non-medical applications. Biomedical sensors detect simple physical
parameters like blood pressure or temperature to blood glucose. Biosensors works by changing
the pH, ions, blood gases (O2, CO2 and etc.), drugs, hormones, proteins, viruses, bacteria,
tumors and etc.
Tissue Engineering
Tissue engineering utilizes the living cells along with engineering methods and suitable
biocompatible and physiochemical factors for improving or replacing biological
tissues(blader,skin,muscles,blood vessels,bone,cartilages).It mainly involves the use of a
scaffold for the formation of new viable tissue for a medical purpose. It performs specific
biochemical functions using cells within an artificially-created support system (e.g. an artificial
pancreas, or a bio artificial liver)
Orthopedic Bio-materials
Orthopedic biomaterials are implantable devices acting as substitutes for the injured or
damaged tissues such as bone,cartilages,joints,ligaments,tendons so as to perform the regular
biological functions at ease. These include hip-knee joint replacements,spine implants, bone
allografts etc. These are biocompatabile,non toxic and non immunogenic synthetic substances.
Cardiovascular Implantable Devices
Cardiovascular is the study related to the circulatory system that includes functioning of heart
and blood vessels (artery,capillaries,veins and veinule),oxygen transport ,carbon dioxide and
waste elimination ,blood pumping,Circulatory loops(pulmonary circulation loop and Systemic
circulation loop),Coronary circulation,Hepatic portal circulation,heart chambers,heart
valves,auricle and ventricle,blood(RBC,WBC,Platelets,plasma). Cardiovascular diseases is the
leading cause of death in most of the developed countries.In cardiovascular applications
biomaterials can be used as heart valves,cardiac pacemaker, stent grafts,vascular grafts,blood
vessel prostheses that improves cardiac function. These are biocompatible and non hazardous
to human body.
Dental Restorative Materials
Dental practises is the healing arts concerned with the teeth and associated structures of the
oral cavity, including prevention, diagnosis, and treatment of disease and restoration of
defective or missing teeth e.g., the restoration of tooth crowns and bridges, root replacements
and surgical procedures performed in and about the oral cavity. Dental restorative materials
can be used for both long and short term applications. The biomaterials should be
biocompatible, bond and match permanently with tooth structure,exhibit similar properties a
sthat of tooth enamel and dentin along with other tissues,capable of initiating tissue repair.
Wound Healing and Skin Regeneration
Wound healing and skin regeneration deals with the structure and function, restoration of
injured or diseased tissues.The healing processes include blood clotting, tissue mending,
scarring, and bone healing. The biomaterials should be biocampatible, non carcinogenic,
painless, inexpensive, bacterials resistant, easily applicable,non antigenic and long shelf life.It
covers the studies and research related to cellular and molecular biology, connective tissue, and
biological mediator studies in the field of tissue repair and regeneration.
Regenerative Medicine
Regenerative medicine restores the structure and functionality of the damaged tissues and
organs. It works on the regeneration of body parts and organs from a person's own cells and
tissues. This eliminates the tissue rejection concept.It covers cell based regenerative
therapies,stem cell transplantation,fetal stem cells,cancer stem cells,bone marrow stem cells
etc.
Ophthalmics Implants
Ophthalmics is the study related to eye tissue.The tissues of the eye can suffer from several
diseases, leading to reduced vision and eventually blindness. Ophthalmics implants are the
biomaterials which are used mainly in contact lenses,intraocular lenses,glaucoma
shunts,Ophthalmic viscosurgical device,retinal prostheses etc. Intralocular lenses is mostly
made of PMM,silicone,elastomer and good vision is restored immediately after the insertion
of lens.