1. The document discusses the use of nanotechnology in oral and maxillofacial surgery. It describes how nanoparticles like quantum dots, nanocomposites, and nanoscaffolds are being used for tissue engineering, imaging, and drug delivery applications. 2. Specifically, it provides examples of how nanoscaffolds made of materials like PLLA are being used to regenerate bone. It also discusses how quantum dots can be used for imaging and labeling cells due to their tunable fluorescent properties. 3. Studies presented showed that nanohydroxyapatite scaffolds promoted bone regeneration in animal models. A bionic ear was also 3D printed using living cells, hydrogels, and silver nanoparticles

1. Journal Club Presentation:
Regenerative nanotechnology in
oral and maxillofacial surgery

2. Brief history of nanoscience and nanotechnology
• It has been suggested that medicine will change more in the next 20 years than it
has in the past. This may be true, as a result of advances in biotechnology and the
recent emergence of nanotechnology.
• The concept of nanotechnology was first introduced by the quantum theorist and
Nobel laureate Richard Feynman in 1959.
• Nanotechnology deals with the manipulation and control of nanomaterials with at
least one dimension below 100 nm.
• Nanosized particles have been incorporated successfully into modern surgical
practice, offering :
1. minimally invasive imaging techniques,
2. improved drug delivery systems and
3. providing a basis for the development of engineered organs.

3. Why nanoparticles are superior to other materials?
• High surface area to volume ratio that confers mechanical, magnetic, optical and chemical
properties superior to those of the original materials.

4. FULLERENES QUANTUM DOTS (QD) NANOCOMPOSITES
They are carbon allotropes that can
adopt different shapes. Eg: Nanotubes
They are man-made nano-crystals
that that can transport electrons.
When UV light hits these
semiconducting nanoparticles, they
can emit light of various colors
depending on its size.
They are multiphase solid materials
where one of the phases has one, two
or three dimensions of less than 100
nm
USE: Combined with an
antithrombogenic surface, carbon
nanotubes are suitable for
applications such as vascular
microcatheters and implants.
USE:
• They can act as drug carriers or
• As labels for cell tracking.
• Suitable for imaging because they
emit fluorescence at different
wavelengths determined by particle
size.
USE:
In tissue engineering, scaffolds are
enhanced by nanoparticulate fillers
which intercalate between layers or
distribute evenly throughout to
maximize surface area for component
interaction.
3 CATEGORIES OF NANOPARTICLES

5. Use of nanotechnology in oral and maxillofacial surgery
In oral and maxillofacial surgical practice nanotechnology has influenced the
development of :
• tissue engineering,
• imaging,
• delivery of drugs

6. 1. Nanoscaffolds for tissue engineering
• Used for regeneration of bone.
• Nanomaterials used to reconstruct bone are:
1. polylactide(PLA),
2. polyglycolide (PGA),
3. polycaprolactone (PCL),
4. Their copolymers poly(lactide-co-glycolide) (PLGA),
5. poly(lactide-co-caprolactone) (PLC),
6. poly(glycolide co-caprolactone) (PGC),
7. poly(L-lactic acid) (PLLA)

7. • PLLA Poly(L-lactic acid) nanofibres (scaffold) facilitate the colonisation of bony
defects and, in combination with BMP-2, increase the generation of bone.
• Nanocomposite = made up of nanostructured magnesium-hydroxyapatite (HA) and
human demineralised bone matrix, was approved for clinical use.
• Nanophase HA has been shown to have improved osteointegrative properties.
• 3 D porous nano HA scaffolds and bone marrow showed adherence, proliferation, and
differentiation of cells, which is promising for the reconstruction of bony defects.
• NanoHA simulates the nanostructure of natural bones, and gives the prospect of better
osteointegration, more natural mechanical properties, less immune reaction, and greater
control of cellular responses.

8. Maxillary Sinus Grafting with a Nano-Structured Biomaterial
Article in European Surgical Research · February 2009
• The clinical study was conducted to evaluate both clinically and histologically
the osteoconductive potential and other properties of a new and entirely
synthetic, nano-structured hydroxylapatite-based biomaterial (NanoBone®) as a
grafting material for sinus floor augmentation.
• Stübinger et al used nanostructured HA-based biomaterial to raise the sinus
floor in 20 patients, and found that the material had excellent biocompatibility
with tissue.
• They noted that within 6 months new trabecular bone had formed with no
need for autogenous bone. The histological analysis showed that the nano
improved biomaterial acted “as a strong osteoconductive bone substitute with
no evidence of an ongoing marked foreign body reaction.”

9. 3D Printed Bionic Ears
Manu S. Mannoor†, Ziwen Jiang†, Teena James§, Yong Lin Kong†, Karen A. Malatesta†, Winston O. Soboyejo†, Naveen Verma‡, David H. Gracias§, and Michael C.
McAlpine†,* †Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544 §Department of Chemical and Biomolecular Engineering,
Johns Hopkins University, Baltimore, MD 21218 ‡Department of Electrical Engineering, Princeton University, Princeton, NJ 08544
• Bionic organs are created due to the ability to combine biological tissue with functional electronics 3
dimensionally.
• These bionic organs have enhanced functions compared to natural organs.
• Conventional electronic devices are inherently two-dimensional, preventing seamless
multidimensional integration with synthetic biology, as the processes and materials are very
different.
• Mannoor et al presented a novel strategy for overcoming these difficulties via additive manufacturing
of biological cells with electronic elements derived from nanoparticles.
• They generated a bionic ear by 3D printing of a hydrogel matrix that was seeded with cells in the
anatomic geometry of human ear , along with an intertwined conducting polymer consisting of
infused silver nanoparticles.
• They did in vitro culturing of cartilage tissue around an inductive coil antenna in the ear, which
subsequently enabled to readout inductively-coupled signals from cochlea-shaped electrodes.
• Overall, the approach suggested a means to intricately merge biologic and nanoelectronic
functionalities via 3D printing.

10. A. Three-dimensional image of a patient’s
ear made using computer-aided design
(CAD).
B. Chrondrocytes, silicone, and silver
nanoparticles were used to create a
bionic ear using 3-dimensional printing.
C. Bionic ear made by 3D
printing.
• They generated a bionic ear by 3D printing of a hydrogel matrix that was seeded with
cells (chondrocytes + silicone) in the anatomic geometry of human ear , along with an
intertwined conducting polymer consisting of infused silver nanoparticles. (Ag
nanoparticles)
• They did in vitro culturing of cartilage tissue around a coiled antenna in the ear, which
subsequently enabled to readout signals from cochlea-shaped electrodes.
• Overall, the approach suggested a means to intricately merge biologic and
nanoelectronic functionalities via 3D printing.

11. TISSUE ENGINEERED AURICULAR RECONSTRUCTION
journal of the American society of plastic joirnals
Plastic and Reconstructive Surgery: March 2014 - Volume 133 - Issue 3 - p 360e-369e
D. The steps involved in making a
tissue-engineered auricular construct
E. Chrondocytes were spray-coated
on to the construct and implanted
into a mouse
Alloplastic implants are used to treat congenital
abnormalities and traumatic injuries.
However, these implants are often associated with
complications, including inflammation, infection,
erosion, and dislodgment.
These results demonstrate that engineered cartilage
tissues can be used as a biological cover for an
alloplastic implant. This system may improve the
structural and functional interactions between the
implant and the recipient's tissues and thus enhance
the outcome of total auricular reconstruction
• A study by Hwang et al showed that tissue-engineered alloplastic implants could form the basis of auricular reconstruction.
• They shaped a commercially available scaffold, MedPor (Porex Surgical Products Group, USA) into an ear.
• The surface was modified by oxidisation to make the scaffold more hydrophilic.
• Fibrin hydrogel and chondrocytes that had been derived from a rabbit’s ear cartilage were then mixed and spray-coated on to the
scaffold.
• The resulting construct was then implanted into a mouse, and the results showed good biocompatibility.

12. Feasibility of using pullulan/dextran nanohydroxyapatite as
a biomaterial for bony regeneration in oral and maxillofacial
applications
• Fricain et al reported a method of developing scaffold made of natural polysaccharides (pullulan and
dextran), which were then incorporated into a nano-hydroxyapatite to yield a macroporous nanocomposite
material.
• In vitro results showed that when human bone marrow stromal cells were cultured on to the nanocomposite
material, they showed an early osteoblastic marker (alkaline phosphatase). This indicated that the scaffold
promoted osteoblastic differentiation of human bone marrow stromal cells.
• The in vivo part of the study involved implantation of the scaffold into a goat with mandibular defect. CT
showed increased mineralisation of bone, and it had completely filled the critical-size bony defect 6 months
after implantation.

13. Role of nanohydroxyapatite as a biomaterial for bony
regeneration
• Pilloni et al also supported the role of nanohydroxyapatite as a biomaterial
for bony regeneration.
• They cultured human osteoblasts derived from alveolar bone on poly lysine
activated nanohydroxyapatite, and found an increase in the expression of
markers of osteoblast differentiation, such as BMP-2 -5,-7, alkaline
phosphatase, and pro-collagen type 1 chain as well as an increase in cellular
adhesion and spreading.
• They concluded that poly lysine-activated nanohydroxyapatite could
function as an osteoinductive material for the growth of bone at sites of
alveolar regeneration.

14. EFFECT OF HYDROXYAPATITE NANO-CRYSTALS ON BONE HEALING AROUND
IMMEDIATE DENTAL IMPLANT
Walid Ahmed Ghanem* , Abd Elnasser Mohamed Hashem** and Mohamed Abo Shabana Mostafa***
EGYPTIAN DENTAL JOURNAL Vol. 62, 2291:2297, April, 2016
• Autogenous bone is regarded as the gold standard for bone graft materials
supplying osteoinductive growth factors, osteogenic cells, and a structural
scaffold.
• However, morbidity in donor site and limitations on obtainable quantities
limit its use.
• Allografts are the next best alternative at present; however, minor
immunogenic rejection and risk of disease transmission are unresolved
issues.

15. • NanoBone is a newly developed bone grafting
substitute consisting of nanocrystalline
hydroxyapatite (HA) and nano-structured silica
(SiO2).
• It was described to be osteoconductive and
biodegradable in a manner comparable to
natural bone remodeling processes.
• Additionally, NanoBone does not induce an
acute inflammatory response of the host
tissue.
• Canullo et al reported that NanoBone®
implanted into 10 patients having sinus lifts
showed good bony regeneration histologically
3 months after implantation.
• Biopsy specimens of bone using trephine burs
were taken after 6 months, and histological
analysis showed the formation of new
trabecular bone. These studies indicate,
therefore, that NanoBone® could be a viable
biomaterial in oral and maxillofacial surgery.

16. Reconstruction of Human Mandibular Continuity Defects With
Allogenic Scaffold and Autologous Marrow Mesenchymal Stem Cells
Barbad Zamiri, DMD,* Shoaleh Shahidi, DMD,Þ Mohamadreza Baghaban Eslaminejad, PhD,þ§ Ahad Khoshzaban, DDS,|| Mehdi
Gholami, DMD,¶ Emad Bahramnejad, DMD,* Reza Moghadasali, MSc,þ Soura Mardpour, MSc,þ and Nasser Aghdami, MD, PhD§
• A novel method for reconstruction of mandibular continuity defect by in vivo tissue engineering.
• In 3 patients with critical-size mandibular bone defects, the allogenic mandibular bone scaffold was
customized, loaded by ex vivo expanded mesenchymal stem cells, and transplanted into the surgical
defect site.

17. Material and method
1. 3 patients with mandibular continuity defect were selected.
2. Two patients had extensive mandibular odontogenic keratocysts, and 1 had an ossifying fibroma
3. Bone marrow (80 mL) was aspirated from the anterior iliac crest of the patient under conscious
sedation and local anesthesia
4. Mesenchymal stem cells were isolated from bone marrow.
5. Fresh-Frozen Bone Allograft was prepared :
• Fresh-frozen mandibular bones were procured from human cadaver donors.
• The bone decortication was performed with a 702-L straight fissure bur at 1-mm distances until the
medullary bone was reached under abundant irrigation to allow better seeding of MSCs and to
facilitate prompt angiogenesis.
• After that, the blocks were immersed in 10% hydrogen peroxide for 24 hours at 38-C.
• Next, the processed blocks were incubated in chloroform for 1 hour at room temperature and then in
0.25% trypsin for 12 hours at 4-C. Blocks were then immersed in 0.5% sodium dodecyl sulfate for 6
hours at room temperature. Each processing procedure was followed by extensive washes with
distilled water. The materials were finally sterilized by 60Co gamma-ray irradiation (20Y25 103 Gy),
and the resultant materials were stored at -70 C until implantation.

18. 6. Surgical Procedure for Implantation of Prepared Allograft Along With Mesenchymal Stem Cells:
• Under general anesthesia, the mandibular defect was exposed through a submandibular neck incision.
After proper dissection and uncovering of the reconstruction plate implantation of the customized bone
allografts with loaded MSCs was performed, and rigid fixation with at least 3 screws to the preexisting plate
was done.
• 5 mL of the prepared solution of MSCs were evenly injected through the holes of the decorticated bone ex
vivo to soak the prepared bone allograft immediately before implantation; another 5 mL was then loaded in
vivo to the construction and surgical bed after implantation.
• Fibrin glue was used to keep the stem cells in place.
• closure was obtained in layers using 3-0 vicryl and 4-0 nylon sutures.

19. Results:
• According to the bone scintigraphy, vascularized bone was identified
in 2 cases.
• According to the serial panoramic imaging, the patients with viable
bone grafts had normal bone healing, whereas the other patient had
progressive overall bone resorption.
• The results demonstrate the feasibility of allogenic bone scaffold
loaded by mesenchymal stem cells in the reconstruction of
mandibular continuity defects. Although long-term results are not yet
available, it may be a novel method of reconstruction and a basis for
further studies.

20. 2. NANOTECHNOLOGY IN IMAGING
• Current imaging techniques for the diagnosis and staging of cancer have their limitations.(fluorescence
imaging - this approach is limited by the poor transmission of visible light through the biological tissue.)
• This has prompted researchers to make use of the NIR optical window (700–1,700 nm) in order to conduct deep-
tissue optical imaging with the aid of QDs (quantum dots)
• Fluorescent semiconductor nanocrystals (QD) have narrow and size-tunable emission spectra that span
from ultraviolet to near-infrared.
• Most conventional organic label dyes do not offer the near-infrared (>650 nm) emission possibility; this
region is highly desired for biomedical imaging due to its reduced light scattering and low tissue absorption,
it is why QDs with their tunable optical properties have gained a lot of interest.

21. QUANTUM DOTS
• Act as carriers of drugs or as labels for tracking cells.
• QD are particularly suitable for imaging, because they emit fluorescence at different wavelengths
depending on the size of the particle.
• Quantum dots (QDs) are man-made semiconductor nano-crystals that that can transport
electrons.
• When UV light hits these nanoparticles, they can emit light of various colors depending on its
size.
Use:
1. To identify tumor cells
2. Use in biomedical fields for diagnostics and drug delivery
3. Use as an anticancer drug carrier
4. In vivo and in vitro bioimaging

22. Why quantum dots (QD) is suitable for non-invasive
imaging?
• Emission spectra span from ultraviolet to near-infrared
• prolonged photostability,
• good photoluminescence,
• high signal : noise ratio (Higher numbers generally mean a better specification, since there is
more useful information (the signal) than there is unwanted data (the noise).
These factors make QD particularly suitable for non-invasive imaging, and
they can be used for identification and long-term in vivo monitoring of
disease in vivo

23. • QD can be attached to paramagnetic ions and used with magnetic
resonance imaging (MRI).
• This combination exploits the high sensitivity of QD fluorescence and
the high spatial resolution of MRI, and acts synergistically to enhance
the reliability of the pictures obtained.
• They can also be conjugated to specific peptides to image specific
tumour cells selectively in vivo.
• This concept may have a role in treatment.

24. Sentinel node biopsy
• QD can be used in the biopsy of sentinel lymph nodes.
• Current methods of detection based on lymphoscintigraphy and
vital dyes can be confused by the autofluorescence of
background tissue.
• QD that emit at the near-infrared region (700-1700 nm) are
associated with a reduction in the autofluorescence of tissue and
can be used in deep tissue imaging, making localization accurate
and sensitive, and subsequent excision of foci of cancer possible.

25. • Kobayashi et al showed that quantum dots could be used as agents for
multicolour molecular imaging in lymph nodes.
• They injected cadmium-selenium (CdSe) and cadmium tellurium (CdTe)
quantum dots into mice, and simultaneously imaged 5 different
lymphatic flows.
• They tracked the distinct lymph nodes using an in vivo spectral imaging
system.
This illustrates the potential for quantum dots to be used as new imaging
agents for cancers of the head and neck.
Reference: Simultaneous Multicolor Imaging of Five Different Lymphatic Basins Using Quantum Dots Hisataka
Kobayashi,*,† Yukihiro Hama,† Yoshinori Koyama,† Tristan Barrett,† Celeste A. S. Regino,‡ Yasuteru Urano,§ and
Peter L. Choyke† Molecular Imaging Program and Radiation Oncology Branch, Center for Cancer Research,
National Cancer Institute, Bethesda, Maryland 20892-1088, and Graduate School of Pharmaceutical Sciences,
The UniVersity of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan Received March 26, 2007; Revised
Manuscript Received May 8, 2007

26. 3. Nanotechnology in the delivery of drugs
• Chemotherapy depends on the circulatory system to transport anticancer drugs to the tumour. There
are negative side effects of this treatment such as non-specificity and toxicity of the drug, whereby
the drugs attack healthy cells and organs as well as the cancerous cells.
• Therefore, targeted drug delivery is being developed as one alternative to chemotherapy treatment.
• The aim of targeted drug delivery is to direct the drug to the specific area where the tumour is
located and thereby increasing the amount of drug delivered at the tumour site and reducing the
side effects.
• In targeted drug delivery, magnetic nanoparticles are used to deliver the drug to its specific
location.
• Generally, the magnetic nanoparticles are coated with a biocompatible layer, such as gold or
polymers, this is done to functionalise the nanoparticles so that the anticancer drug can either be
conjugated to the surface or encapsulated in the nanoparticle.
• Once the drug-nanoparticle complex is administered, an external magnetic field is used to guide the
complex to the specific tumour site. The drug is released by enzyme activity or by changes in pH,
temperature or osmolality.

27. • Once the drug-nanoparticle
complex is administered, an
external magnetic field is used to
guide the complex to the specific
tumour site.
• The drug is released by enzyme
activity or by changes in pH,
temperature or osmolality

28. Structure of a thernostic nanoparticle-
therapeutic+diagnostic nanoparticle
Theranostic nanoparticles can be functionalized with antibody and polymers to achieve targeted delivery
and improved biocompatibility.
The interior core of nanoparticles can be encapsulated with various bioactive compounds, such as nucleic
acids, imaging contrast agents, drugs, and fluorescent materials to fulfill different theranostic purposes.

29. liposomes and drug-conjugated nanoparticles for the
treatment of cancer
• Liposomes are lipid bilayers that are spherically arranged and have the capacity to encapsulate drugs
within their inner aqueous phase.
• Liposomes coated with PEG (polyethylene glycol) and incorporating the anthracycline doxorubicin
have lower cardiotoxicity and greater efficacy than the free drug.
• This formulation is currently being used in a clinical trial for breast cancer
Reference: Liposomes and nanoparticles: nanosized vehicles for drug delivery in cancer
Author links open overlay panelYogeshkumarMalam12MarilenaLoizidou2Alexander
M.Seifalian123

30. Gelatin hydrogel as a drug delivery system to increase bony
regeneration in mice with mandibular distraction.
Kimura A, Kabasawa Y, Tabata Y, Kazuhiro Aoki , Ohya K, Omura K, Gelatin hydrogel as a carrier of recombinant human fibroblast growth factor-2 during rat mandibular
distraction, Journal of Oral and Maxillofacial Surgery (2014), doi: 10.1016/j.joms.2014.03.014.
• Kimura et al evaluated its feasibility.
• Recombinant human fibroblast growth factor-2 (rhFGF-2) was incorporated into gelatin hydrogel and
inserted into the distracted area.
• Radiographic and CT imaging after 29 days showed that bony formation in the distracted area had
increased.
• Histological examination also showed increased bony regeneration.

31. Potential side effects and limitations of
nanotechnology
• The long-term health implications of nanoparticles must be investigated
thoroughly.
• For example, the size of a nanoparticle may mean that the blood–brain barrier
can be crossed.
• Large surface area:volume ratios make nanoparticles biologically active, which
may lead to inflammation and oxidative stress.
• For successful tissue engineering, scaffolds must be developed that are capable
of providing the necessary oxygen and nutrients to densely packed cells in whole
organs.
• As we delve into the nano-world, several issues and challenges must be
addressed before nanotechnology can become commonplace. For instance,
nanotoxicology is an intense area of research that seeks to elucidate the possible
side effects of using nanoparticles, and their biological interactions with the
human body.

32. CONCLUSION
• Regenerative nanotechnological uses in oral and maxillofacial surgery
are increasing rapidly, and there have been recent exciting
breakthroughs.
• Within nanotechnology, two broad areas of research can be
identified:
• the use of multifunctional theranostic nanoparticles for head and
neck cancer, and
• the use of nano inspired biomaterials for improving bony
regeneration specifically for oral and maxillofacial surgery.

33. Thank you