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Anatomy and Formation of Bone

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Video 1: Bone Anatomy
Good morning everyone, I am Hemalatha Kanniyappan, doing my research under the guidance of Dr.Vignesh Muthuvijayan. Today I will be explaining about Bone Tissue Engineering.I start with a brief introduction about bone and its functions. What is a bone? Bone isa substance that forms the skeleton of the body, to be more clear, it is a natural compositematerial that is composed of organic collagen phase and inorganic hydroxyapatite phase.The hardness of the bone is mainly due to the presence of hydroxyapatite, which is composedchiefly of calcium phosphate and calcium carbonate; whereas, the toughness and the viscoelasticbehaviour is mainly due to the presence of collagen.The major function of the bone as we all know it is the, it makes the foundation for ourbodily locomotion and it acts as the load bearing capacity to our skeleton. It protectsthe internal organs; it also houses the biological elements that are required for haematopoiesis,which is the process that are responsible for the formation of blood cellular components.It traps the dangerous metals; for example, lead and also it maintains the homeostasisof key electrolytes whereas, like it maintains the equilibrium between the cellular components.In addition of above all the function, bone is engaged in a constant cycle of resorptionand renewal, that will be called as bone as a dynamic in nature.So, the defect in bone and the treatment of bone defects due to severe trauma or severalpathological disorders like bone tumour or infection possesses a major threat to thesurgeons worldwide and it is a serious health problem, global health problem. Amongst thetransplants made, bone is considered to be the second mostly transplanted tissue afterblood. Bone loss due to damage is a serious challenge to orthopaedic surgeons especiallywhen the bone loss is massive. Bone grafting is the commonly used surgical method to enhancebone regeneration. Over 2 million bone, bone grafting procedures are performed worldwidein every year. The treatment of bone grafting includes autograftingwhereas; where we graft a tissue from the same individual it is considered to be thegold standard treatment. Because, of its ideal biocompatibility in terms of structural aswell as immunological point of view. And the second higher option is allografts, wherewe graft a tissue from different individual of same species. Though autografts or allograftsare considered to be the standard treatment for bone grafting, but in autograft it requiresthe harvest of harvest of site, it not only increases the pain. But, also increases thetime of surgery, bleeding and donor site morbidity; it also leads to nerve injuries at multipleharvest sites due to surgeries.Whereas in case where we need a large amount of tissue to be transplanted, it cannot bedone using autograft procedure because the availability of the tissue is limited; whereas,in allograft it is associated with pathogen transfer and also immune rejection. So, weneed an better option treating option to enhance bone regeneration or to repair the bone defects,we need an option where it overcomes the all other above said limitation.Tissue engineered synthetic bone substrates were developed which will ideally eliminatethe above said limitation and aims to develop an ideal bone graft that enhance bone regeneration.Before getting into tissue engineering aspects of our bone tissue engineering application,its status, issues ,we need to understand the anatomy of bone.So, in this session I will be explaining about the anatomy of the bone and the modellingand remodelling of the bone. Then the later session will be discussing about tissue engineeringaspects.The anatomy of the bone, the first gross anatomy. Gross anatomy means the study of anatomy ofthe bone at the visible level. The structure of long bone explores the best visualizationof all parts of the bone. The long bone is divided into two parts; diaphysis and theepiphysis. The diaphysis, the tubular region that runs between the proximal and the distalends of the bone. And, the hollow region in the diaphysis is called as medullary cavitywhich is filled with yellow bone marrow. And, the walls of the diaphysis is made up of hardand dense compact bone. And, the wider section of the wider sectionsat the bone, at the each side of the bone is the epiphysis. It is filled with red marrowand it is filled with spongy spaces, the cavity is filled with spongy spaces and red marrowfills these spaces. And, each an epiphysis connect to the diaphysis at the metaphysis.Metaphysis is the narrow area which has epiphysial growth plate and then cartilage layer, hyalinecartilage layer. This epiphysial growth plate becomes an epiphysial line when a bone growthstops at an early adulthood, for approximately at the age of 18 to 21 years and the hyalinecartilage layer replaced with an osseous tissue. The inner; the medullary cavity, the intramembranous is made up of intra membranous lining ,delicate membranous lining calledendosteum.Where it is the place for bone growth, repair and remodelling occur which where I will explainbone growth repair and remodeling in detail. What are the cellular components involvedin later session, later part of the session.And, the periosteum - the fibrous membrane cover the outer surface of the bone. It hasblood vessels, nerves, lymphatic vessels that nourish the compact bone. This periosteumcovers the entire outer surface of the brain, outer surface of the bone except at the epiphysisregion where it has articular cartilage. And, this acts as the shock absorber and reducesthe friction.Whereas flat bones like cranium it is made up of a layer of a spongy bone and lined oneither side of the layer of the compact bones. So, the layer of spongy bone and the two layersof the compact bone works together to protect the internal organs. If there is any fracturein the outer cranial bone still the brain is protected by the inner contact layer ofthe compact bones.And the surface features of the bone, bone markings. There are three general classesof bone markings: articulations, projections and holes. As the name implies the first classof bone marking articulation as the name implies where two bones surfaces come together. Thesesurfaces tend to confirm to one another such as one being grounded the other being cupedother being curbed. In order to facilitate the function of articulation; articulationmeans joint for example, knee joint. And the second bone marking class generalclass is called as projections. It is an area that projects above the surface of the bone;tendons and ligaments are attached to the periosteum to this through this marking. Forexample, the process of spinous process of vertebra is an example of projection kindof bone marking. And, the third general class of bone marking is holes where it is an openingor groove in bone that allow the nerves or blood vessels to enter the bone. For example,foramen, where the blood vessels passes through the bone.The next we need to discuss about bone cells and tissue which plays a major role in tissueengineering aspects; we need to know about what are the cells present in the bone. So,as I explained in the introduction session, bone is made up of collagen and hydroxyapatite.Hydroxyapatite gives the gives bone their strength and hardness and whereas, collagengives them flexibility. If hydroxyapatite is not there, the bone will become more elastic.If collagen is not there, the bone will become brittle. Bone is composed of a smaller volumeof cells. Although the bone composed of a smaller volume of cells it plays a very importantrole in the nth function.There are four types of cells; osteocytes, osteoblast, osteogenic cell and osteoclastcells. Osteoblasts cells are the bones cells responsible for the formation of bone. Itis present in the growing structures and it is called osteocyte and which is the primarycell for the mature bone. And, the places where the osteocytes located are called aslacunae. Osteocytes maintain the mineral concentration within the matrix. Osteoblast and osteocytescommunicate with each other and exchange their nutrients through the long cytoplasmic processesvia canaliculi which is canaliculus which is present inside the bone matrix. Both osteocyteand osteoblast lack mitosis, then there rise the question, if both the cells lack mitosishow are they replenished when old one dies? The answer lies in the third category, thirdproperty of cell which is osteogenic cell. It is highly undifferentiated cell and itis present in the deep marrow present in the deeper regions of periosteum and marrow cavities.It is the only bone cell that can divide, it divide and differentiate into osteoblastcells. So, while explaining the function of bone the last function where I said bonusis dynamic in nature, which means the new bone is constantly formed and the old bonethat or the damaged bone or the repaired bone should be resorbed continuously, which was,which is done by the cells called osteoclast cells. Osteoclast cells are responsible forbone resorption. So, there should be a constant balance betweenosteoblast cells which are responsible for the formation of new bone and osteoclast cellswhich are responsible for the bone resorption in order to maintain the structural integrityof the bone.So, this reviews the cell type, its function and location in the bone. First cell typeis osteogenic cells, as I said it is the only cell that can divide and it develop into osteoblast.It is present in the deep layers of periosteum and the marrow. And, the next is osteoblastscells which are responsible for the formation of bone and present in the growing portionsof bone including periosteum and endosteum. Osteocytes which are the primary cell fora matured bone and the location where it is located it is known as lacunae.And, it maintains the mineral concentration of matrix which are entrapped in matrix. Osteoclastscells are responsible for bone resorption and it is present at the bone surfaces andat sites of old injured or unneeded bone. These osteoclasts cells are formed from monocytesor macrophages which are two white blood cells, they are not originated from osteogenic cells.And, the details of compact and spongy bone are well explored by its histology. The compactbone is the stronger bone of the two and it gives support and protection. And it is denser,stronger than the spongy bone, it is found under the periosteum and diaphysis of thelong bone. The microstructural unit of compact bone is called as osteon, it is called asosteon. Each osteon is made up of concentric rings of calcified matrix; this is also calledas haversian system. These osteon is made up of concentric rings called lamellae, concentratedrings of calcified matrix which are called as lamellae, ok.Running towards the centre canal of the osteon, centre to the osteon it is the central canalwhere central canal where it has blood vessels, lymphatic vessels and nerves. This is alsocalled as haversian canal and this blood vessel, nerve and branches of at the right anglesthrough the Volkmann canal or perforating canal which connects to the periosteum orendosteum. The osteocytes present in the lacunae arefound at the adjacent of the lamellae of the osteons. So, as I explained earlier the nutrientsexchanged is done by canaliculi. So, one canaliculi is connected to another canaliculi, eventuallyto the central canal where it has this blood vessels and lymphatic vessels. And osteocytes,the osteocytes is nourished with the presence of this blood vessels, lymphatic vessels andnutrients are transported through the central canal.Whereas, spongy bone it is also called as cancellous bone unlike the compact bone spongybone is not made up of concentric rings whereas it is made up of lattice like network of matrixspikes called trabeculae. This provides strength to the bone, the spaces in some spongy boneswhich that contains red marrow which are protected by the trabeculae where haematopoiesis occurs.Haematopoiesis is nothing, but the process of formation of blood cellular components.Blood supply and nerve supply to the bone. The spongy bone and medullary cavity receivenourishment from arteries that pass through the compact bone. The osteocytes the arteriesenter through the nutrient foramen which is the small opening that present in the diaphysis.The osteocytes present in the spongy bone get nourished by the blood vessels and thearteries that enter through the periosteum and into the marrow cavities. Once it passesthrough the marrow cavities and it is collected by the veins and it is pass out from the bone.Similarly, nerves also follow the same paths into the bone, where they tend to concentratein the more metabolically active regions of the bone. Nerves also sense pain; the nervesalso plays a very important role in regulating blood supplies and bone growth.

Video 2: Modelling and Remodelling of Bones
So, with this the brief explanation about or the detailed explanation about bone anatomyis done. Now, we move on to the formation of bone which is modelling and remodelling.Bone is first; initially bone is formed by modelling, it is developed in two distinctways: intramembranous pathway and endochondral pathway. In either of the cases, there isa mesenchymal cellular condensation occurs and it serves as the template for the formationof bone. In first intramembranous bone where mesenchymal stem cells are directly developedinto osteoblast cells and subsequent bone formation occurs.For example: bones in mandible, clavicle or few cranial bones are formed by this process.Whereas, in endochondral bone endochondral pathway where most of the bones like longbones in our body occurs formed through this pathway. Where, the mesenchymal progenitorcells developed into chondrocytes, first they are developed into chondrocytes. Then theyform a cartilaginous layer, cartilaginous matrix, calcified matrix, then they subsequentbone formation occurs. So, these are the two pathways where the formation of bone occurs.Then the remodelling of bone takes place, we know that the skeleton is a metabolicallyactive organ that undergoes continuous remodelling throughout the life. This remodelling is necessaryin order to maintain the structural integrity as well as to maintain the mineral concentrationwithin the matrix. Remodelling of bone begins at the early fetal stage and also once theskeleton is fully formed in young adults, afterwards all the metabolic activity willtakes place in this form.This remodelling consists of highly regulated series of; this consists of series of highlyregulated steps which involves the interaction of two cell lineages, two cell lineages.They are mesenchymal osteoblastic cells and hematopoietic osteoclastic cells. The interactionbetween mesenchymal osteoblastic cells and hematopoietic osteoclastic cells precursorscells leads the it the start of the remodeling phase. And, there are four phases in remodellingof a bone: activation phase, resorption phase, reversal phase and formation of the phase.The first phase is the activation phase where the interaction between the two precursorscell lines happens. So, which results in the formation, differentiation, fusion of andformation of the large osteoclasts cells. Osteoclast cells which are present at thesurface of the bone matrix, these cells will tend to secrete hydrogen ions, hydrogen ionsas well as the lysosomal enzymes. Especially cathepsin C, cathepsin K; cathepsin K thesetwo will degrade all bone cellular components including collagen at low pH. And, this isthe resorption phase, the resorption phase where the cells interact with the hematopoieticprecursors to form osteoclasts and the reversal phase the complete resorption takes place.The complete resorption of bone by osteoclasts takes place in the reversal phase and initiatesthe formation phase. In this formation phase, mesenchymal osteoblasticcells will form, will start to produce osteoblasts, which which fills the cavity which are resorbedby the osteoclasts thereby it laid down the bone matrix. So, this how the remodellingof bone occurs; the first is the interaction of between two precursors cell lines whichis hematopoietic osteoclasts cell and mesenchymal osteoblasts. And then they form the osteoclastscells. This osteoclast cell involve in bone resorption and it resorbs the bone matrixcompletely whereas, there is an formation of osteoblast cells which fills the cavityof the bone resorbed matrix. So, this is how bone modelling and remodelling, formationof bone occurs.If there are any abnormalities present in this bone remodelling will lead to variousskeletal disorders. For example, osteoporosis, hypothyroidism and hyperthyroidism, hyperparathyroidismand hyperthyroidism, Paget disease, orthopaedic disorders, osteopetrosis. These are the skeletondisorders which are due to abnormalities happen in the bone remodelling cycle. So, osteoporosis- osteoporosis is defined as the loss of bone mass and strength which leads to the increasein propensity to fracture. It is type 1 and type 2; type 1 is called as postmenopausalosteoporosis and type 2 is called as senile osteoporosis.Recently studies have, literature have proved that deficiency of oestrogen which is theimportant systemic hormone for the bone turnover; if there is deficiency of oestrogen it leadsto osteoporosis. So, this deficiency or the osteoporosis reasons can be mainly due tothree reasons; one the peak, peak bone mass is not formed completely or there is a imbalancebetween osteoclast function and osteoblast function or the over activeness of osteoclast.Like over osteoclasts are activated too much thereby it resorbs bone more than the boneformation, that is osteoporosis. And, Paget disease again they complete mechanism or theclear mechanism is not yet understood. But, they say that the because of some viralinfection this osteoclast cells are activated abnormally and thereby bone resorption ismore, where it changes the structural structure of the bone, where it shows in the evidentin that picture that is Paget disease. In osteopetrosis, osteoblasts function is lost,loss of osteoblast function; bone formation is not that great when compared to bone resorption.So, there should be a balance between the formation of bone or the resorption of bone,in order to maintain a proper shape of the bone; otherwise it will lead to a varietyof skeletal disorders.So, now I will be explaining about normal process of bone healing. So, bone once thereis any fracture, bone can itself heal by its process. It can be repaired by the processof both intra membranous and endochondral bone formation. It first it starts with thehematoma formation accompanied by the inflammatory response, then it start recruiting the signallingmolecules. For example: interleukin, fibroblast growth factors, bone morphogenetic proteinswhich are responsible for the formation of bone.Once after recruiting signalling molecules at the place of cortex and periosteum intramembranous formation, bone formation immediately occurs. Then it stabilizes the fracture bythe formation of callus which is under which with by chondrogenesis. Chondrogenesis isthe activation of chondrocytes which is highly similar to endochondral ossification.Then once the tissue reaches its maturity, the chondrocyte proliferation decreases andthey calcify the matrix, the growing blood vessel which carries chondroclasts and osteoblasticprogenitors. This chondroclasts will resorb the calcified cartilage and whereas, the osteoblasticprogenitors will helps in the formation of new bone and the remodelling of new bone willstarts; so, thus by it heals the repair or fracture.As we know that bone is highly vascularized tissue, though it can heal by itself beyondcertain point or beyond critical point clinical intervention is required; where the futuretreatment option is bone tissue engineering. Bone tissue engineering is considered to bethe future treatment option. In next session we will be discussing about is status or keycomponents involved in the bone tissue engineering. Thank you.