II year B.E Biomedical Engineering, Agni College of Technology, Chennai, India
Received: 26 May, 2016; Accepted: 15 September, 2016; Published: 16 September, 2016
R Leela, II year B.E Biomedical Engineering, Agni College of Technology, Chennai, India, Tel: 7299257526; E-mail:
Leela R (2016) Biomaterial and Regenerative Medicine Approaches to Restoration of Flexion in Lumbar Herniated Disc. Glob J Biotechnol Biomater Sci 2(1): 019-024.
© 2016 Leela R. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Objective: The systematic objective of this paper is to restore flexion in vertebral bone and to nourish the nucleus pulposus through the approach of biomaterial and regenerative medicine.
Method: Studies were made on the treatment of lumbar herniated disc in CINAHIL, PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and Cochrane Database of Systematic Reviews(CDSR). This paper provides methods for restoration of flexion in the bone. A biomaterial scaffold made of poly-β-hydroxybutyrate (PHB) consisting of extracellular matrix (ECM) proteins which is synthesized in vitro through regenerative medicine is replaced in the place of degenerated disc. The scaffold model is designed in CAD and then printed in LAB. The metabolic functions of the disc are performed by the scaffold.
Results: Fifteen papers, published between 2004 and 2014 were included in this study. Disc height restoration is possible using biomaterial and tissue engineering but none of the papers provide reports on flexion of the bone. The treatment of non-operative modalities like physical therapy, anti-inflammatory medications and steroid injections still results in low back pain. The surgical methods like Joint arthroplasty and non-fusion techniques spare motion but not restore normal spine biomechanics. The study shows that the treatment with cells and biomaterials shows better results.
Conclusion: Both the non-operative and surgical methods do not provide a good result. They do not offer flexion in the bone. The use of biomaterial scaffolds with ECM proteins paves a way for the medical professionals to treat lumbar herniated disc.
Degeneration of lumbar herniated disc is often associated with low back pain which affects up to 80% , of people. Acute pain recover within 10 weeks while chronic low back pain last for longtime. About 10% of people suffer from chronic low back pain . In United States , the annual health care in case of chronic low back pain cost for 20 billion USD. The aging of the disc decreases [4,5], the cell density of the Nucleus Pulposus (NP) in the disc which in turn decline the production of extracellular matrix(ECM) proteins. The Nucleus Pulposus is covered by annulus fibrosus which is responsible to bear stress. The secretion of extracellular matrix contains proteins such as type 2 collagen  and aggrecans , which is the backbone of proteoglycan. There is also a pivotal role of the vertebral endplates in disc degeneration. The endplates are located in the cranial and caudal ends of each disc that separates the vertebral bone form the disc and prevents bulging of nucleus into adjacent vertebrae. The solute transport and maintenance is controlled by the proteoglycan molecules within the matrix. The blood vessels in the endplates are activated by degrading metalloproteinase (MMP) enzyme which are maintained in latent form by tissue inhibitors. The calcification of the vertebral endplate tremendously becomes less permeable for oxygen and nutrient supply , resulting in further degeneration of the disc . The compressiblity of the disc is retarded due to the loss of hydrophilic proteoglycans within the NP cells. The recent treatments include the non-operative modalities such as physical therapy , anti-inflammatory medication  and steroid injection . Surgical methods are used when there is a failure in the non-operative modalities. Surgical treatments include partial discectomy to spinal fusion [13,14], disc arthroplasty and non-fusion techniques spare motion and cannot restore normal spine biomechanics. So, there is no long term benefit . Degeneration of disc is an important problem because the human beings face difficulty in their routine life.
Previous research [16-18], was focused on gene based delivery of growth factors into NP cells. Recent research focus on the combination of biomaterial and regenerative medicine based approach to degenerative disc disease to restore disc height. This approach helps in restoring disc anatomy and ECM production within the disc. Although disc height is possible to restore, the flexion in the disc is still a limitation. Hence the significance of this paper is restoration of flexion in the disc by using a special type of biomaterial along with the regenerative medicine as a scaffold which is replaced in the place of degenerated disc.
The NP cells [19,20] or bone marrow derived mesenchymal stem cells  are harvested and expanded in vitro and also coupled with poly-β-hydroxybutyrate which becomes a biomaterial scaffold and replaced in the place of degenerated disc.
The systematic objective of this paper is to restore flexion in the lumbar herniated disc through the combination of tissue engineering and biomaterial based approach. The primary end point is the restoration of the herniated disc to normal healthy disc and to improve tissue quality.
Materials and Methods
Composition of NP cells
The study deals with the method of replacing the herniated lumbar disc by combining biomaterial and regenerative medicine as a scaffold. The normal disc provides two major macro-molecular components in the extracellular matrix. The normal disc contains approximately 70% , proteoglycan and water content in the Nucleus Pulposus which is lesser in the Annulus fibrosis. The collagen network consist of type I and type II collagen fibrils which provides high tensile strength to the disc and anchors the tissue to the bone. Aggrecan is responsible for maintaining tissue hydration through osmotic pressure provided by its constituent chondroitin and Keratan Sulphate chains. Other collagen types are III, V, VI, IX, X, XI, XII, XIV, small proteoglycan such as lumican, biglycan, decorin and fibromodulin and other glycoproteins such as fibronectin and amyloid. The matrix is broken down by metalloproteinases(MMP) enzyme and aggrecans which also synthesize by disc cells. In degenerated disc type II collagen becomes denatured.
The level of decorin and biglycan is elevated in degenerated human disc. Fibronectin content increases with increasing degeneration and it becomes more fragmented. Therefore the level of proteoglycans is restored by stimulating the proliferation of NP cells by combining biomaterial and tissue engineering. The proteoglycans have an attraction to water and restores the normal biochemical environment and becomes rich in oxygen and nutrient supply. The combination of NP cells and poly-β-hydroxybutyrate as a scaffold is replaced in the place of degenerated disc by surgery. This helps in holding the vertebral bodies together. So, the disc becomes like a normal disc. Even in the case of injury the portion of scaffold is not injured and is very safe for human beings.
Poly-β-hydroxybutyrate is a polyhydroxyalkanoate a polymer belonging to polyesters class. PHB is probably the most common type of polyhydroxyalkanoate. PHB is produced by microorganisms such as Ralstonia eutrophus, Methylobacterium rhodesianum or Bacillus megaterium. The polymer is a product of carbon assimilation and is employed by microorganisms as a form of energy storage molecules to be metabolized when other common energy sources are not available. They have the property of resisting to biodegradation. They have good oxygen permeability therefore replacing it in the place of degenerated disc helps to nurture the cells with oxygen and nutrients. They have a melting point of 175 C and a glass transition temperature of 2 C which does not affect the body temperature of humans. Their tensile strength is 40 MPa close to that of polypropylene and so they are capable of bearing high tensile strength.By introducing the NP cells into poly-β-hydroxybutyrate and growing them in vitro and then replacing it in the place of degenerated disc the flexion in the disc is restored.
Cell based therapies
Main approach is to achieve cellular repair of the degenerated disc matrix. One approach is to stimulate disc cells to produce more matrix. It increases the rate of synthesis of matrix up to fivefold. Cytokines lead to loss of matrix because they inhibit matrix synthesis which stimulate agents that are induced in breakdown. The cell based therapies , are more advantageous than gene based therapies because it has to suite all persons.
Rapid prototyping technology
Products for making a biomaterial scaffold can be made through computer aided designing (CAD) in 3D and then it can be implemented in laser assisted bio-printing for printing the scaffold. The laser assisted bio-printing , setup is composed of a Nd:YAG laser, a microscopic objective and a ribbon positioned onto an XYZ translation stage. Each layer of the 3D image represents the shape of the cross-section of the model at a specific level. Rapid Prototyping technology is variously called solid free- form fabrication (SFF) or rapid manufacturing (RM). CAD enables computational modeling and finite element analysis (FEA) prior to fabrication. In this paper PHB biomaterial is scaffolded with NP cells and manufactured by rapid prototyping technology and then it can be implemented in the place of herniated disc.
Fifteen papers published between 2004 and 2014 are included in this study. The search produced 744 papers in total. It includes one hundred and forty three publications. Two foreign papers cannot be obtained.
Usually the investigation is made on few animals that develop disc degeneration spontaneously, such as the sand rat and chondrodystrophoid dog. Many biomaterials are related to help in recurring spinal problem. Among them poly-β-hydroxybutyrate plays a major role in providing the surface for attachment of extracellular matrix and proliferation of cells. The poly-β-hydroxybutyrate provides high tensile strength like the Annulus Fibrosis which would help in protecting Nucleus Pulposus consisting of the extracellular matrix proteins. Most of the papers deals with PLGA biomaterial which helps in delivering and proliferation but flexion along with stability is not there in PLGA. Disc height restoration is possible using PLGA but flexion is the bone is still a question. So, the remedy for that is Poly-β-hydroxybutyrate Table 1.
Figure 1 shows the schematic representation of the adult disc. It is a normal disc in a healthy human beings.