Introduction (under the following heads) 211.

Origin of the proposal: There are roughly 1 million cases of skeletal defects a year that require bone-graft procedures to achieve union.[30] Socioeconomic consequences in treating these patients with bone fractures is a major concern for both USA and EU, which will increase in the next years due the ageing of their population. Current treatments are based on autologous bone grafts, autogenous bone grafts or as an alternative to these, metals and ceramics.[30 34] Autologous bone graft, that is, bone taken from another part of the patients own body, has been the gold standard of bone replacement for many years because it provides osteogenic cells as well as essential osteoinductive factors needed for bone healing and regeneration. [33,35] It is commonly taken in the form of trabecular bone from the patients iliac crest, but cortical bone can be used as well.[33,36] However, and although it presents relatively good percentages of success, the spectrum of cases in which it can be used is restricted, mainly due to the limited amount of the autograft that can be obtained and due to donor site morbidity.[3034] Allograft, bone taken from somebody elses body, could be an alternative. However, the rate of graft incorporation is lower than with the autograft. Allograft bone also introduces the possibilities of immune rejection and of pathogen transmission from donor to host, and although infrequent, infections could occur in the recipients body after the transplantation. [3034,37] As an alternative to these two bone grafts, there are metals and ceramics.[30] However, both of them do present several disadvantages. Metals, for instance, although providing immediate mechanical support at the site of the defect, exhibit poor overall integration with the tissue at the implantation site, and can fail because of infection or secondary due to fatigue loading.[30] On the other hand ceramics have very low tensile strength and are brittle and, Autologous bone graft, that is, bone taken from another part of the patients own body, has been the gold standard of bone replacement for many years because it provides osteogenic cells as well as essential osteoinductive factors needed for bone healing and regeneration. [33,35] It is commonly taken in the form of trabecular bone from the patients iliac crest, but cortical bone can be used as well.[33,36] However, and although it presents relatively good percentages of success, the spectrum of cases in which it can be used is restricted, mainly due to the limited amount of the autograft that can be obtained and due to donor site morbidity.[3034] Allograft, bone taken from somebody elses body, could be an alternative. However, the rate of graft incorporation is lower than with the autograft. Allograft bone also introduces the possibilities of immune rejection and of pathogen transmission from donor to host, and although infrequent, infections could occur in the recipients body after the transplantation. [3034,37] As an alternative to these two bone grafts, there are metals and ceramics.[30] However, both of them do present several disadvantages. Metals, for instance, although providing immediate mechanical support at the site of the defect, exhibit poor overall

integration with the tissue at the implantation site, and can fail because of infection or secondary due to fatigue loading.[30] On the other hand ceramics have very low tensile strength and are brittle and, thus they cannot be used in locations of significant torsion, bending, or shear stress.[30] Hence it is clearly seen that an adequate bone replacement is yet to be found and it is at the same time urgently needed for full recovery of the patients. A possible solution for these problems may be in TE. [30] M. J.Yaszemski, J. B. Oldham, L. Lu, B. L. Currier, Bone Engineering, 1st edition, Em squared, Toronto 1994, p. 541. [31] R. Spitzer, C. Perka, K. Lindenhayn, H. Zippel, J. Biomed. Mater. Res. 2002, 59, 690. [32] G. C. Simon, C. A. Khatri, S. A. Wight, F. W. Wang, J. Orthop. Res. 2002, 20, 473. [33] F. R. Rose, R. O. Oreffo, Biochem. Biophys. Res. Commun. 2002, 292, 1. [34] H. Petite,V.Viateau,W. Bensaid, A. Meunier,C. de Pollak, M. Bourguignon, K. Oudina, L. Sedel, G. Guillemin, Nature Biotech. 2000, 18, 959. [35] I. Asahina, I. Seto, M. Oda, E. Marukawa, A. M. Imranul, S. Enomoto, Bone Engineering, 1st edition, Em squared, Toronto 1999, p. 526. [36] G. P. Reece, C. W. Patrick, Jr., Frontiers in Tissue Engineering, 1st edition, Pergamon, Oxford 1998, p. 166. [37] D. F. Williams, Bone Engineering, 1st edition, Em squared, Toronto 1999, p. 577. v 212. Definition of the problem The science of bone grafting and bone biomaterials has provided extraordinary therapies for patients who have suffered bone loss through traumatic injury, bone cancer, or birth defects. In fact, bone and bone materials are the most commonly transplanted materials after blood transfusions. From late seventeenth century skull grafts to modern bone bioengineering, scientists have taken their cues from fundamental physiology and even sea coral to develop replacements for bone. 213. Objective 220. Review of status of Research and Development in the subject 221. Internaional status 222. National status 223. Importance of the proposed project in the context of current status 224. Review of expertise available with proposed investigating group/institution in the subject of the project 225. Patent details (domestic and international) 230. Work plan 231. Methodology 232. Organisation of work elements 233. Time schedule of activities giving milestones (also append to bar diagram and mark it as Section 410) 234. Suggested plan of action for utilization of research outcome expected from the project.

Biomaterial scaffolds for constructing tissues and cell delivery Bioactive biodegradable scaffold material for bone regeneration. Despite recent technological advances, thousands die each year while waiting for organ transplants due to lack of donor organs or efficient organ substitutes (Thomson et al. 1995). Although clinicians have tried to replace the function of failing organs mechanically (dialysis and heartlung bypass machines), or through implantation of synthetic replacements (blood vessel and joint replacements), these are often only temporary solutions and do not allow the patient to completely resume normal activities (Thomson et al. 1995). Infection and device rejection are also serious concerns in such procedures (Ishaug-Riley et al. 1997). Despite recent technological advances, thousands die each year while waiting for organ transplants due to lack of donor organs or efficient organ substitutes (Thomson et al. 1995). Although clinicians have tried to replace the function of failing organs mechanically (dialysis and heartlung bypass machines), or through implantation of synthetic replacements (blood vessel and joint replacements), these are often only temporary solutions and do not allow the patient to completely resume normal activities (Thomson et al. 1995). Infection and device rejection are also serious concerns in such procedures (Ishaug-Riley et al. 1997). Approximately half million bone grafting procedures are performed each year in the United States. The number is increasing as life expectancy and the number of baby boomers is aging. Traditionally, bone grafting is performed using autografts, allografts and bone substitutes, which include bone cements and fillers. However, there are serious drawbacks with these existing graft options. To overcome the limitations, the bone tissue engineering approach has been proposed for bone defect repair and regeneration. In this approach, aside from the bone-forming cells and growth factors, the healing and regeneration of critically sized bone defects require a scaffold, which not only allows bone in-growth, but also provides mechanical support. Dr. Nukavarapus focus has been to design and fabricate biodegradable scaffolds that are fully osteoconductive and mechanically compatible for bone repair and regeneration. Also, he is working to develop hybrid scaffold systems that are load-bearing and, at the same time, has the ability to deliver both, the required cells (vasculogenic and osteogenic), and growth factors (BMP-2 & VEGF). Such self-sustaining scaffolds could be directly implanted in vivo, thus, completely bypassing the in vitro culture step. The ultimate goal of this research is to develop biodegradable grafts that accelerate bone defect repair and yet, are clinically and economically viable. This project aims is to synthesize bioactive and biodegradable scaffold material helpful in regeneration of bones and its characterization using spectroscopic techniques. Orthopaedic prostheses made of bioinert materials have been in use with tremendous fifteen-year survivability of 7585. Metal alloys, polymers and medical grade ceramics are being used, which has improved the quality of life for many patients. However, an increasing percentage of our ageing population require greater than thirty years survivability of devices. It is proposed that in order to meet this growing need for very long-term orthopaedic repair that a standard change is needed to shift from replacement of tissues to regeneration of tissues. This method consists of biological based tissue repair requires an alternative approach based upon use of bioactive materials for tissue (hard) regeneration.

Bone damage can occur due to injury or disease, and damaged bone does not always heal back to its original quality. Traditional repair and replacement methods include autografting, allografting, and distraction osteogenesis. However, these processes can be long, painful, and have the possibility of being rejected by the body. A new method of repair and replacement that is being researched is bone tissue engineering, in which autologous osteoblasts or cells that can become osteoblasts are grown on porous permanent or temporary scaffolds. In the past, traditional procedures, such as autografting, allografting, and distraction osteogenesis, were used to replace or repair damaged bone tissue. Grafting involves replacing damaged tissue with harvested tissue from donor or from another location within in the body. Distraction osteogenesis is a lengthy and painful process in which the two sides of a bone fracture are separated a small distance every few weeks until the desired length of bone has been regrown. Man-made devices, such as bone cement fillers and prosthetics made of metals, ceramics, and polymers, were also used for replacing or repairing bone tissue. Approximately fifteen years ago, biologists and engineers merged to form a new field called tissue engineering (Langer et al., 1993). Bone tissue engineering involves growing osteoblasts or cells that can become osteoblasts on porous permanent or temporary scaffolds. The cells would come directly from the patient, eliminating problems of immunological rejection, pathogen transfer, and lack of donor cells. The scaffolds provide physical supports on which the cells can grow in three-dimensional constructs, and it is hoped that the cells will develop into new tissue with the same mechanical and chemical properties as native bone. If engineered bone can be developed successfully in the laboratory, scaffolds, autologous cells, and bone tissue engineering could then be used to treat patients with bone injuries or diseases in the clinical setting.