Bioengineering in Healthcare

BINF 704, Fall 2015Team #6

Abhinav Rawat Sithalechumi Narayanan

Outline• Introduction• Materials and Methods

– Emergence of Biomaterials in Healthcare– Third Generation Biomaterial and Their Applications in

Healthcare• Advantages of Bioengineering• Case Studies - Myocardial Tissue engineering - Bioengineered Blood Vessel• Disadvantages of Bioengineering• Conclusion• Reference• Questions

Introduction• Bioengineering encompasses two closely related

areas of interest– it applies the principles of engineering science to

understand how living organisms function and – it applies engineering technologies to design and

develop new devices like diagnostic or therapeutic instruments or formulation of novel biomaterials for medical applications, design of artificial tissues or organs and development of new delivery systems.

• Overall bioengineering focuses on the uses of biomaterials or similar types of materials or principles to improve the healthcare services

Introduction Cont..• Biomaterial in medical terminology is “any natural or

synthetic material (which includes polymer or metal) that is intended for introduction into living tissue especially as part of a medical device or implant” .

• So in general biomaterials are the devices those are used to improve the general healthcare of society and are fabricated by the process that employs or mimics biological phenomenon.

• They are being used for the healthcare applications from ancient times. But subsequent evolution has made them more versatile and has increased their utility.

Introduction Cont…

Biting ants where used as Surgical sutures in 9500 B.C to hold human tissue together.The Mayans in 600 A.D used Blue Narce Shell as a way of fixing a lost or damaged tooth.

Introduction Cont…..

Emergence of Biomaterials in Healthcare

• Biomaterials are being used in healthcare area from a long period of time. However, visible progress was made in the area of biomaterials since 1940s and substantial development has been observed in therapeutic medical technologies and implant devices over the past 25 years.

• Over the years there is a transition from the use of metals to natural tissues or their derivatives and mechanical valves are being replaced by prosthetic valves made from bovine tissue or harvested porcine valves.

Cont…• Developments with sensor technology and software algorithms have now

enabled the pacemakers (for Arrhythmia, irregular heart beat) to automatically respond to varied levels of patient’s physical activity so that they can alter the stimulation rate accordingly.

Cont…

• As the blood brain barrier does not allow medication to enter the central nervous system (CNS), fully implanted programmable pumps are used to deliver precise doses of drugs like morphine to reduce severe pain.

One of the most remarkable applications of biomedical engineering in the area of healthcare over last decade is deep brain stimulation for the treatment of degenerative diseases like Parkinson. These implantable pumps are also being used for the treatment of non-malignant and cancer pain.

Third Generation Biomaterial and Their Applications in Healthcare

First generation of biomaterials evolved during 1950s and 1970s for their application as medical implants. Basic goal during the fabrication of these biomaterials was to maintain a balance between physical and mechanical properties together with minimal toxicity to host tissue.

Ideal properties of the first generation biomaterials sought by surgeons were (1) appropriate mechanical properties; (2) resistance to corrosion in aqueous environment; and (3) should not elicit toxicity or carcinogenicity in living tissue.

1960 Charnley uses PMMA, ultrahigh- molecular-weight polyethyl end, and stainless steal for total hip replacement.

Second Generation

• Second generation biomaterials were developed to be bioactive.

• A substantial progress was observed in the application of these materials for orthopedic and dental usage.

• Examples include bioactive glasses, ceramics, glass-ceramics

and composites.

Third Generation• Further developments with the biomaterial technology are now translating into

the expansion of third generation biomaterials those can stimulate specific cellular response.

• For example, artificial tissues being fabricated by placing cells within scaffold materials, which help guide cell proliferation and differentiation.

• . Efforts are also being made to develop scaffolding materials those possess Nano-scale features in order to mimic the native extracellular matrix of the host.

• Currently major focus of the researchers is the development of artificial tissues (as biomaterials) those have architectural features same as the natural counterpart.

• Development and use of biomaterials is expected to augment in coming years. New prognostic methods are being developed and are becoming available to assist the progress of innovative approaches for an affordable healthcare.

Applications of BioengineeringApplication For

Myocardial Tissue Engineering Cardiac Repair

Orthopedic and Musculoskeletal Medicines

Bone Repair, muscles, tendons

Skin Tissue Regeneration Skin Repair

Disposable Medical Devices Biodegradable material

Drug eluting Stents Deliver Drug in a controlled manner

Implantable Biosensors Detect and monitor Biomarkers

Polymer Therapeutics Drug delivery systems

Lab on a Chip Several Lab Functions on a single chip

Gene Therapy Repair ailing tissue or organ

Advantages of Bioengineering• Bioengineering is one of the most viable option which has a

potential to improve the existing healthcare scenario. • It uses biomaterials and tissue engineering concepts for the

repair of damaged tissue.• Major goal here is to repair or regenerate the tissue or

organ than to remove it. • Bioengineering has also shown a good progress in

diagnostics and newer methods are being developed which can make the detection easy and accurate.

• With the current progress in biomaterials we expect a future healthcare which will be available at an affordable price and with better services.

Outline • Introduction• Materials and Methods

– Emergence of Biomaterials in Healthcare– Third Generation Biomaterial and Their Applications in Healthcare

• Advantages of Bioengineering• Case Studies - Myocardial Tissue engineering - Bioengineered Blood Vessel• Disadvantages of Bioengineering• Conclusion• Reference• Questions

Case study 1 – Myocardial Tissue Engineering

• Recently tissue engineering is evolving as a potential therapy for cardiac repair. Research activities have attempted to regenerate the ailing heart with epicardial implantation of bioengineered tissue patch pre-seeded with bone marrow cells or BM-derived mesenchymal stem cells.

• Both natural and synthetic polymers like collagen, fibrin, PGA, PLGA etc are being used for these applications. Animal derived tissues like bovine pericardia in combination with engineered cell sheet to create a sandwich like cardiac patch is also being used to regenerate ischemic heart in rat model.

Schematic representation of use of cardiac

bandages/patches for treatment of ischemic heart

Whole heart bioengineering?• Scientists at the MMRL are at the leading edge in the quest to

bioengineer a human heart for transplantation. • The team has two ultimate goals. - One, to further advance the methodology and generate acellular heart

scaffolds of human size. - Two, to repopulate these acellular heart constructs with heart cells

derived from the skin of patients and ultimately generate fully functional human-size hearts suitable for transplantation.

• The Director of the Stem Cell Center at the MMRL, is working to reprogram fibroblasts from human skin biopsies so as to create billions of heart cells and cardiovascular progenitors derived from induced-pluripotent stem cell (iPS) that will be used to repopulate the scaffolds in the process of generating new hearts.

New scaffold technologies Hydrogels are the broad

class of cross-linked polymeric networks those absorb large amount of water or any other biological fluid without showing any alternations in their 3-D architecture. Retention of water by hydrogels makes them appropriate for various biomedical applications.

Hydrogels as Promising Scaffolds for Healthcare Applications

• A study used rats with damaged hearts and attempted to fix the damage by injecting their cell-laced hydrogel, “re-muscularizing” the area and fixing the characteristic damage of a heart attack.

• When injected into the hearts of rats, the hydrogel saw about 73% of the stem cells survive, compared with just 12% survival while suspended in a normal injection fluid.

• This hydrogel allows the cells to live and grow, installing themselves in the body and integrating healthily. Heart-damaged rats injected with hydrogel-loaded stem cells saw a 15% increase in pumping efficiency for the treated ventricle, compared with just 8% for regularly used stem cell therapies.

Case Study 2 – Bioengineered Blood Vessel

Bioengineered Blood Vessel• A team of doctors at Duke University Hospital helped create a

bioengineered blood vessel and implanted it into the arm of a patient with end-stage kidney disease.

• The new vein is an off-the-shelf, human cell-based product with no biological properties that would cause organ rejection.

• The vein is engineered by cultivating donated human cells on a tubular scaffold to form a vessel. The vessel is then cleansed of the qualities that might trigger an immune response.

• When implanted in animals, the vein grafts actually adopt the cellular properties of a blood vessel. They don’t just elude rejection; they become indistinguishable from living tissue as cells grow into the implant.

Few other Case studies• Regenerating a new kidney – there are hundreds of

thousands of patients suffering from kidney disease. - NIDDK supported researchers to break new grounds on this

front by first stripping cells from a donor organ and using the remaining collagen scaffold to help guide the growth of new tissue. To regenerate viable kidney tissue, researchers seeded the kidney scaffolds with epithelial and endothelial cells.

- The resulting organ tissue was able to clear metabolites, reabsorb nutrients, and produce urine both in vitro and in vivo in rats. The creation of transplantable tissue to permanently replace kidney function is a leap forward in overcoming the problems of donor organ shortages and the morbidity associated with immuno-suppression in organ transplants.

Few other case studies - continued• Skin tissue regeneration - Adipose derived stem cells (ADSC’s)

is other potential cell source which has shown a capacity to stimulate both collagen synthesis and migration of dermal fibroblasts together with improved wrinkling and wound healing property in vivo.

• Chronic non-healing diabetic foot ulcers – severe complication – limb loss. Current standard methods of treatment are aimed at controlling infection. Healing rates are poor with standard treatment. A new strategy - tissue engineering - allowing the application of healthy living skin cells to assist in the healing process. Dermagraft (Smith & Nephew) is a neonatal-derived bioengineered tissue comprised of dermal fibroblasts.

Conclusion• Current healthcare and diagnostics has many constraints like

it is expensive, has limited accuracy or there is no strategy to treat some of the diseases (e.g., cancer). So there is a great demand to improve the current healthcare facilities.

• It is one of the most viable option which has a potential to improve the existing healthcare scenario. It uses biomaterials and tissue engineering concepts for the repair of damaged tissue.

• It has also shown a good progress in diagnostics and newer methods are being developed which can make the detection easy and accurate. With the current progress in biomaterials we expect a future healthcare which will be available at an affordable price and with better services.

Disadvantages of Bioengineering

Disadvantages of Bioengineering• One of the main arguments against bioengineering is

that humans are not fit to play the role of god. • Legal, ethical limits to bioengineering is still debated.• Expensive• Requires time consuming research• On one hand, bioengineering raises hopes for

dramatic improvements in various human conditions. On the other hand it raises fears of a ‘Brave New World’ in which the human essence is lost.

Bioengineering – unethical?

Regenerative medicine can be used to treat/repair but if it was to be used to enhance human race, for example: germ line gene therapy, then it becomes unethical.

Future!!!

References• Bhat S, Kumar A. Biomaterials and bioengineering tomorrow’s healthcare.

Biomatter. 2013;3(3):e24717. doi:10.4161/biom.24717.• Marston, WA. Dermagraft, a bioengineered human dermal equivalent for

the treatment of chronic nonhealing diabetic foot ulcer. Expert Rev Med Devices. 2004 Sep;1(1):21-31.

• http://www.nibib.nih.gov/science-education/science-topics/tissue-engineering-and-regenerative-medicine

• https://allscienceconsidered.wordpress.com/2009/11/28/bioengineering-the-key-to-a-better-life-or-frankensteins-monster/

• http://news.harvard.edu/gazette/story/2007/03/legal-ethical-limits-to-bioengineering-debated/

• http://www.extremetech.com/extreme/215033-new-hydrogel-can-keep-stem-cells-alive-for-heart-repair

• https://www.mmrl.edu/organ-bioengineering/• http://www.humacyte.com/press/surgeons-at-duke-university-hospital-i

mplant-bioengineered-vein/

Questions??