Biomedical Engineering For Bone Repair Tissue Engineering: Management, Progress, And Challenges

Tissue engineering management and progress for repairing bone defects

Discuss about the Biomedical Engineering for Bone Repair Tissue Engineering.

A vibrant tissue with competency to cure, maintain and restructure itself is popularly known, as ‘Bone’ of our body is really an ultimate smart tissue. The elaboration, conservation and restoration of this tissue depend on three categories of cell that are osteoblasts, osteocytes and osteoclasts.  

As per global context, there are roughly more than 100 million cases of bone defects each year leading to the requirement of bone repair procedures. The autologous and allogeneic bone grafts are traditional methods of bone repair but they persist certain limitations and poor outcomes. However, the advances of tissue engineering process in last few decades have increased the possibility of in vitro bone repair and regeneration (Enderle and Bronzino, 2012).

In a simple understanding, tissue engineering is a combination of life sciences plus biological engineering approaches to develop biological substitutes. In comparison to traditional biomaterials approach the tissue engineering provide an advantage of innovative purposeful tissue construction instead only providing the implant of new replacement part making this technique an innovation in medical sciences (Reis and Cohn, 2012).

Figure 1: General process of Bone tissue engineering

(Source: Enderle and Bronzino, 2012,p.34)

The dynamic qualities of bone and advance processes of bone tissue engineering show a great compatibility to overcome the persisting bone disorders. Currently, after blood, bone is the second tissue-engineering transplant forming a hope for medical science. But, still this technique also involves certain challenges (Enderle and Bronzino, 2012). In this essay, a detailed study on management and progress of tissue engineering in bone repair followed by the challenges and future aspects of this technique are done.

According to Amini et al. (2012), the specific goal of bone tissue contriving is to raise in vitro bone culture possibilities by applying innovative engineering approaches. In few recent decades, a wealthy progress is achieved in bone tissue engineering related to cell sources, biodegradable scaffolds, biocompatibility achievements, advanced bioreactors and identification of specific growth factors to produce bone in artificial conditions as well as natural conditions. The bone tissue engineering process simply involves three major aspects that involve processes to select stem cells, scaffolds formation and biological conditions development to achieve ideal, robust, reproductive and functional bone repair. Correia et al. (2012) studied that bone tissue engineering firstly involves the formation of scaffold that is a medium providing specific architecture and environment for tissue regeneration. There are various materials like ceramic, metals and polymers that are widely used for scaffold formation until the emergence of biodegradable polymers.

Barriers in bone repair tissue engineering

Bose et al. (2012) opine that there are natural occurring as well as artificially constructed biodegradable polymers that are ideal for scaffolds formation in tissue construction persisting properties like osteoinductivity, biodegradability, biological compatibility and porosity. The use of these biodegradable polymers in TE scaffolds formation is the most important achievement in bone tissue engineering process. The biodegradable scaffolds are formed from different materials that perform functionality with specific culture cells. Some of the most commonly used biodegradable scaffold materials are collagen, chitosan, starch, polyhydroxybutyrate, fibrin etc. A more determined biodegradable scaffolds are considered as the future trend in tissue engineering progress.

Liu et al. (2013) studied that in initial times of tissue engineering the production of scaffolds remained a complex issue the traditional grafting technique provided less compatibility with biological materials. However, in recent times, the use of phase inversion, fibre bonding, high-pressure methods and freeze-drying are miracles in the tissue-engineering arena. Correia et al. (2012) opine the method of PLGA-poly (lactide-co-glycolide) scaffold formation using the phase inversion techniques. The scaffold produced through this technique is wide used in tissue engineering process.

Figure 2: PLGA scaffold formation by using phase inversion technology

(Source: Correia et al. 2012, p.2484)

Further, the use of fibre bonding, injection moulding, melt-based technologies etc. is a progressive technique for scaffold formation.

Amini et al. (2012) indicated that the limitations of using osteoblasts as an inducer of tissue engineering are overruled by the incoming of stem cells technology in artificial bone construction field. The use of stem cells is considered as most valid and promising solution for tissue making processes. Construction of bone from mesenchymal stem cell (MSCs) is one of the recent developments in tissue engineering field. The MSC being adult stem cells are widely present in bone marrow further named as BN-MSCs cells. These cells are widely used in tissue engineering to produce bone graft through applying technique of making artificial tissues in scaffolds that further undergo oestrogenic culture. Correia et al. (2012) further studied the practice of Adipose derived stem cells (ADSCs) in tissue making processes is another advantage because these stem cells have capabilities to critical size defects repair in both femoral and calvarial bone segment defects (Zhang et al. 2012).

Bose and Tarafder (2012) studied the advances in bone tissue engineering by getting exceptional growth factors that work to produce in vitro bone cultures. The absence of effective growth factors limited the process of bone regenerations like cell adhesion, migration and differentiation. But, now the use of insulin growth factor I&II and platelet derived growth factor (PDGF), fibroblast growth factors (FGFs), bone morphogenetic proteins (BMPs),and  transforming growth factor beta (TGF-β) provides effective bone regeneration process. Further, Shin et al. (2012) indicated that the custom of bioreactors for making tissues artificially works as a new advancement to mimic the in vivo environment dynamics. These bioreactors are constructed to develop conditions and architectures that support tissue regeneration. Some of the most successful bioreactors till date are spinner flask bioreactor, static flask bioreactor, and rotating wall container bioreactors in bone tissue engineering.

Figure 3: Static flasks, spinner flask and rotating wall vessel bioreactor used for in suit bone tissue construction

(Source: Shin et al. 2012, p.260)

The need of an experimental model to test the performance of technique is an essential component as well as limitation in biological research. Getting appropriate experimental models is a tough process in experimental science, Szpalski et al. (2012) stated that use of animal models is a new advancement to test the reliability of bone tissue engineering protocol. The experimental model should be feasible and should have high similarity index. Some of the most widely used animal models are subcutaneous model from rats and rabbit calvarial models that are widely used these days for testing the bone tissue engineering protocol. Tripathi and Basu (2012) studied that collaboration of gene therapy with bone tissue engineering helps to overcome the genetic defect along with bone disorder. The basic process involves delivery of specific proteins through viral vectors in the bone regeneration stages.

The bone tissue engineering process is the future of transplantation technology and is emerging as a new medical treatment approach but still it persist certain limitations that are holding back the progressiveness of this technology. Szpalski et al. (2012) studied that surgeon on everyday basis faces common challenges like reabsorption, infections, immunogenic reactions and insufficient vascularization while performing bone grafting in tissue engineering process. Liu et al. (2013) studied that bone tissue engineering is a highly expensive process that is not affordable on the regular basis due to an expensive high-quality bone, lack of donor, repeated failure of bone graft and use of expensive instruments. Making this technique cost-effective is becoming a challenge for scientists. Marolt et al. (2012) indicated in their study that failure of bone graft is a major challenge that is essential to get controlled in tissue regeneration process. The reason behind the failure of bone graft still remains a mystery. Sometimes it is considered as a failure of appropriate biomaterial selection, wrong scaffold or improper in vitro conditions or growth factors delivery making the establishment of bone graft a challenge in technology. Szpalski et al. (2012) identified the confronts in artificial bone construction protocol that involves premature aging and differentiation of osteogenic cells, lack of control over cell viability and proliferation in 3D scaffolds, lack of knowledge on control parameters for cultivated human bone marrow behaviour under in vivo environment. Further, Liu et al. (2013) stated that in vivo transplantation of regenerated bone tissue is another barrier in establishing successful bone tissue engineering process. There are unknown biological processes that refuse the in vitro bone graft in animal model experiments.

The bone tissue engineering technology is considered to be a complex and complicated structural arrangement process. There are different cell types, biomaterials, MSCs, growth factors and other factors that work together in this process. However, in last few decades, tissue engineering attained a considerable progress in utilizing bioactive factors, scaffolds development, getting potent cell source, suitable biomaterials and bioreactors. But now the future relies on overcoming the challenges of technique. Liu et al. (2013) studied that currently the shift of scientific minds is to develop improved vascular creation in this field if artificially created bones because it is the priority essential factor for graft existence. Nguyen et al. (2012) neo-bone tissue always survive in regions having the vascular network, therefore, it is important to induce vascularization under in vitro conditions of bone formation.  

Liu et al. (2013) stated that induction of angiogenesis and vasculogenesis is another future emerging theme because these processes work at in vivo conditions to develop new blood vessels. The development of artificial angiogenesis and vasculogenesis will help to control the in vivo graft rejection. Therefore, it is another important future aspect of bone tissue engineering process. According to Szpalski et al. (2012), there are on-going researches to establish scaffold that promotes vascular formation. Marolt et al. (2012) studied the research is done to utilize stem cells for neo-vascularisation where endothelial progenitor/stem cells are been utilized for generating vascularized bone graft by co-culture systems and combined linkages with osteogenic cells in different scaffolds to produce neo-vascularisation as a future trend in bone tissue construction process.

Conclusion

In present era, there is essential requirement of effective clinical treatments for severe bone defects at global scenario but there are limitations in established technologies like autograft and allograft. In last two decades that has been a remarkable positive progress in bone tissue engineering process annually making it a hope for getting better clinical treatment for bone repair.

In the recent times there are remarkable achievements in bone tissue engineering procedures and technologies but still this field of medical science is in its developing state. More concentration is required to overcome the deficits in technologies like better scaffolds, more effective bioreactors, better stabilizing enzymes and laboratory condition to get 100% in suit transplantation or bone grafting done successfully. Tissue engineering holds a promising approach to provide better medical treatment for disease like cancer, diabetes etc. which are still in incurable state.

The so far success for this technique is encouraging, whereas the challenges and future aspects are giving this technology a new height in clinical application. It is expected that in near future tissue engineering will acquire a successful in vivo bone graft transplantation and bone fracture repair treatment.

References

Books

Enderle, J.D. and Bronzino, J.D., 2012. Introduction to biomedical engineering. Academic press.

Reis, R.L. and Cohn, D., 2012. Polymer based systems on tissue engineering, replacement and regeneration (Vol. 86). Springer Science & Business Media.

Journals

Amini, A.R., Laurencin, C.T. and Nukavarapu, S.P., 2012. Bone tissue engineering: recent advances and challenges. Critical Reviews in Biomedical Engineering, 40(5).

Bose, S., Roy, M. and Bandyopadhyay, A., 2012. Recent advances in bone tissue engineering scaffolds. Trends in biotechnology, 30(10), pp.546-554.

Bose, S. and Tarafder, S., 2012. Calcium phosphate ceramic systems in growth factor and drug delivery for bone tissue engineering: a review. Acta biomaterialia, 8(4), pp.1401-1421.

Correia C, Bhumiratana S, Yan LP, Oliveira AL, Gimble JM, Rockwood D, Kaplan DL, Sousa RA, Reis RL, Vunjak-Novakovic G. 2012. Development of silk-based scaffolds for tissue engineering of bone from human adipose-derived stem cells. Acta biomaterialia, 8(7), pp.2483-92.

Liu, Y., Lim, J. and Teoh, S.H., 2013. Review: development of clinically relevant scaffolds for vascularised bone tissue engineering. Biotechnology advances, 31(5), pp.688-705.

Marolt, D., Campos, I.M., Bhumiratana, S., Koren, A., Petridis, P., Zhang, G., Spitalnik, P.F., Grayson, W.L. and Vunjak-Novakovic, G., 2012. Engineering bone tissue from human embryonic stem cells. Proceedings of the National Academy of Sciences, 109(22), pp.8705-8709.

Nguyen, L.H., Annabi, N., Nikkhah, M., Bae, H., Binan, L., Park, S., Kang, Y., Yang, Y. and Khademhosseini, A., 2012. Vascularized bone tissue engineering: approaches for potential improvement. Tissue Engineering Part B: Reviews, 18(5), pp.363-382.

Shin, S.H., Purevdorj, O., Castano, O., Planell, J.A. and Kim, H.W., 2012. A short review: recent advances in electrospinning for bone tissue regeneration. Journal of tissue engineering, 3(1), pp. 260-65.

Szpalski, C., Wetterau, M., Barr, J. and Warren, S.M., 2012. Bone tissue engineering: current strategies and techniques—part I: scaffolds. Tissue Engineering Part B: Reviews, 18(4), pp.246-257.

Szpalski, C., Barbaro, M., Sagebin, F. and Warren, S.M., 2012. Bone tissue engineering: current strategies and techniques—part II: cell types. Tissue Engineering Part B: Reviews, 18(4), pp.258-269.

Tripathi, G. and Basu, B., 2012. A porous hydroxyapatite scaffold for bone tissue engineering: Physico-mechanical and biological evaluations. Ceramics International, 38(1), pp.341-349.

Zhang, Z.Y., Teoh, S.H., Hui, J.H., Fisk, N.M., Choolani, M. and Chan, J.K., 2012. The potential of human fetal mesenchymal stem cells for off-the-shelf bone tissue engineering application. Biomaterials, 33(9), pp.2656-2672.