Accelerated tissue repair

Accelerated Tissue Repair
21st Century Strategies for Rapid Injury Recovery


Webinar Outline

• Understanding the Mechanisms

• Nutritional/Dietary Necessities

• Nutraceutical Agents for Accelerated Tissue Repair

• Exogenous Nutrients for Accelerated Tissue Repair

Understanding the
Mechanisms
Regeneration vs. Repair

• Regeneration refers to the proliferation of cells and
tissues to replace lost structures

• If tissue injury is severe or chronic, and results in
damage of both parenchymal cells and the stromal
framework of the tissue, healing can not be
accomplished by regeneration. Under these
conditions, the main healing process is repair by
deposition of collagen and other Extra Cellular
Matrix (ECM) components, causing the formation of
a scar.

Understanding the
Mechanisms
Regeneration vs. Repair

• Repair most often consists of a combination of
regeneration and scar formation by the deposition of
collagen.

• Scar formation is the predominant healing process
that occurs when the (ECM) is damaged by severe
injury. Chronic inflammation stimulates scar
formation because of local production of growth
factors and cytokines that promote fibroblast
proliferation and collagen synthesis, and because of
accompanying damage to the ECM. The term
fibrosis is used to describe the extensive deposition
of collagen that occurs under these situations.

Understanding the
Mechanisms
Extra Cellular Matrix

•ECM components are essential for wound healing, because
they provide the framework for cell migration, maintain the
correct cell polarity for the re-assembly of multilayer
structures,4 and participate in the formation of new blood
vessels (angiogenesis).

•Cells in the ECM (fibroblasts, macrophages, and other cell
types) produce growth factors, cytokines, and chemokines that
are critical for regeneration and repair.

•Tissue repair and regeneration depend not only on the activity
of soluble factors, but also on interactions between cells and
the components of the extracellular matrix (ECM). The ECM
regulates the growth, proliferation, movement, and
differentiation of the cells living within it.

Understanding the
Mechanisms
Extra Cellular Matrix

•The ECM is composed of three groups of macromolecules:
fibrous structural proteins, such as collagens and elastins that
provide tensile strength and recoil; adhesive glycoproteins that
connect the matrix elements to one another and to cells; and
proteoglycans and hyaluronan that provide resilience and
lubrication. These molecules assemble to form two basic forms
of ECM: interstitial matrix and basement membranes.

• The basic structural unit of a collagen fiber consists of long
protein chains assembled from amino acids, such as proline,
lysine,hydroxyproline, hydroxylysine, cysteine, and glycine

•The replication of cells is stimulated by growth factors or by
signaling from ECM components through integrins (receptors
that mediate attachment between a cell and the tissues
surrounding it.)

Understanding the
Mechanisms
Growth Factors

•The proliferation of many cell types is driven by
polypeptides known as growth factors

•Most important growth factors involved in tissue
regeneration and repair:

7.Epidermal Growth Factor (EGF) and Transforming Growth
Factor a (TGF-a)
8.Hepatocyte Growth Factor (HGF)
9.Platelet-Derived Growth Factor (PDGF)
10.Vascular Endothelial Growth Factor (VEGF)
11.Fibroblast Growth Factor (FGF)
12.Transforming Growth Factor b (TGF-b) and Related Growth
Factors (Cytokines)

Understanding the
Mechanisms
Transforming Growth Factor b (TGF-b)

•TGF-b is a potent fibrogenic agent that stimulates
fibroblast chemotaxis, and enhances the production of
collagen, fibronectin, and proteoglycans. It inhibits collagen
degradation by decreasing matrix proteases and increasing
protease inhibitor activities.

•TGF-b has a strong anti-inflammatory effect but may
enhance some immune functions.

•In vivo studies have confirmed that TGF-beta1 increases
granulation tissue, collagen formation, and wound tensile
strength when applied locally or given systemically

Nutritional/Dietary
Necessities

• Vitamins and Minerals

• Amino Acids

• Essential Fatty Acids

• Bioflavonoids/Antioxidants

• Anti-inflammatory foods

Nutritional/Dietary
Necessities

Vitamins and Minerals

• Zinc, magnesium, and vitamin B-12 are key micronutrients
in the formation of RNA and DNA. Deficiencies of these
nutrients block the initiation of collagen production.

• Vitamin C is used to link amino acids in protein synthesis.
Vitamin C also stimulates secretion of collagen from cells
and is required for the hydroxylation of procollagen.

• Manganese is a trace mineral which is pivotal in
connective tissue production. In humans, manganese
concentrations are highest in connective tissue.

Nutritional/Dietary
Necessities

Vitamins and Minerals

• Vitamins B-6 and B-2 along with copper are used for the
cross-linking of the collagen fibers which make this protein
strong.

• Vitamin E supplementation may reduce free radical
damage and benefit wound healing and connective tissue
repair.(Bucci, 1995)

• A copper enzyme important to connective tissue is lysyl
oxidase, which is involved in the cross-linking of elastin
and collagen, a role that is necessary for proper collagen
formation and maintenance (Linder, 1991)

Nutritional/Dietary
Necessities

Amino Acids

• Long protein chains made from amino acids make up the
basic structural unit of a collagen fiber.

• Additional amounts of the sulphur containing amino acids
are recommended, due to the fact that they are the three
most important amino acids for the production of collagen,
of which the ligaments are composed.

• Vitamin C along with iron, is necessary for hydroxylation of
proline and lysine, both essential amino acids in the
formation of collagen.

Nutritional/Dietary
Necessities
Essential Fatty Acids (EFAs)

• N-3 fatty acids are essential for normal growth and
development and may play an important role in the
prevention and treatment of coronary artery disease,
hypertension, diabetes, arthritis, other inflammatory and
autoimmune disorders, and cancer (Simopoulos et al.,
1986; Galli and Simopoulos,1989; Simopoulos, 1991;
Simopoulos et al., 1991; Galli et al., 1994a,b; Salem et al.,
1996).
• Consumption of long chain n-3 polyunsaturated fatty acids
decreases the amount of arachidonic acid in cell
membranes and so available for eicosanoid production.
Thus, n-3 polyunsaturated fattyacids decrease production
of arachidonic acid-derived eicosanoids (Calder, 2006).

Nutritional/Dietary
Necessities
Essential Fatty Acids (EFAs)

• Beneficial Dietary Sources of long chain n-3
polyunsaturated fatty acids include flax (ground or oil), fish
and fish oils, eggs, wheat grass, EPA and DHA from micro
algae sources.

• Although the long chain n-3 polyunsaturated fatty acids are
needed more due to a lack in the typical Western diet, a
balance between 3,6,9 fatty acids is still necessary for
optimal physiology.

Nutritional/Dietary
Necessities
Bioflavonoids/Antioxidants

• Once known as "Vitamin P" and semi-essential
nutrients.4000 flavonoid compounds have been
characterized and classified. Group of plant pigments that
are largely responsible for colors of many fruits and
flowers.
• Most common categories are: Anthocyanidins, Citrus
bioflavonoids (flavonones) and Flavonols (Quercetin ,
Polyphenols, etc.)

• Bioflavonoids are thought to benefit connective tissue by
binding to elastin, preventing its degradation by elastases
released as a result of inflammation (Tixier et al, 1984).

Nutritional/Dietary
Necessities
Bioflavonoids/Antioxidants

• Many of the biological effects of flavonoids appear to be
related to their ability to modulate cell-signaling pathways,
rather than their antioxidant activity.

• Dietary sources of flavonoids include fruits (especially
berries and citrus), vegetables, tea, red wine, cocoa and
legumes.

• Antioxidants reduce activation of NF kappa B, thereby
preventing up-regulation of cytokine production by
oxidants. This lends to the prevention of excess
inflammation (Grimble, 1994).

Nutritional/Dietary
Necessities
Anti-Inflammatory Foods

• “The first step in the treatment of a ligamentous injury is to
decrease inflammation” (Anderson, 1990).

• Anti-inflammatory dietary sources include: fruits (especially
berries and citrus), vegetables (including sea vegetables),
teas, good oils, certain nuts, seeds and spices.

• Avoid the most pro-inflammatory foods like: refined sugar,
trans fats, refined grains, most vegetable cooking oils
(safflower, soy, corn, sunflower, etc.), pasteurized dairy,
feedlot –raised meat, processed meats, food additives
(MSG, Aspartame, etc)

Nutritional/Dietary
Necessities
Anti-Inflammatory Foods

• Use anti-inflammatory spices liberally. Top choices
include; Turmeric, Ginger, Cayenne, Black Pepper,
Cinnamon, Rosemary, Basil, Cardamom, Chives, Cilantro,
Cloves, Garlic and Parsley.

• Curcumin from Turmeric lowers the levels of two enzymes
in the body that cause inflammation and is also a powerful
antioxidant.

• Research has shown curcumin to be a highly pleiotropic
molecule capable of interacting with numerous molecular
targets involved in inflammation (Jurenka, 2009).

Nutraceutical Agents for

• While the compounds previously discussed can be found in whole
foods and should definitely be incorporated into the diet, quality and
content can vary significantly.

• For these reasons, and to enhance the potential of the various
compounds to elicit more rapid tissue repair, we need targeted,
standardized whole food nutraceutical supplements to augment and
enhance the dietary intake.

• Potency, digestibility, quality and method of manufacture are all
important considerations when selecting nutraceutical agents for the
most profound clinical outcomes.

Colostrum

• Bovine colostrum is a fluid secreted during the first few
days following calving. It is rich in immunoglobulins, growth
factors, cytokines, and confers immune protection to the
newborn calf from opportunistic infections. Besides
providing immune support, colostrum has remarkable
muscular-skeletal repair and growth capabilities

• Studies have shown that colostrum is the only natural
source of two major growth factors namely, transforming
growth factors alpha and beta, and insulin-like growth
factors 1 and 2. These growth factors have significant
muscle and cartilage repair characteristics. They promote
wound healing with practical implications for trauma and
surgical patients (Uruakpa et al., 2001).

Colostrum

• Growth factors and cytokines present in colostrum and
their respective actions are as follows:

• Epidermal Growth Factor (EGF) Stimulates tissue repair
& wound healing and maturation of the digestive tract
• Insulin Growth Factor 1 & 2 (IGF1 & IGF2) Stimulates
muscle and bone cell proliferation and development.
• Fibroblast Growth Factor (FGF) Stimulates muscle and
bone cell proliferation and development
• Platelet Derived Growth Factor (PDGF) Stimulates the
proliferation and development of a wide range of cell types
Transforming Growth Factor (TGF) Stimulates tissue
repair & wound healing

Colostrum

• The IGF-I in bovine colostrum contains the identical amino
acid segment on the front of the bovine molecule which,
when split by digestive acids in the human stomach,
releases a molecule identical to human IGF-I (Ley, 1997).

• Insulin-Like Growth Factor 1 (IGF-1) functions to stimulate
muscle and bone cell proliferation and development -
helps to build muscle and strong bones

• It appears that joint-related problems, that originally were
helped with glucosamine and then declined, improved
when they were given colostrum. From research, it
appears that IgF, is essential for the utilization of the
glucosamine, and without adequate amounts of it, the
continued use of glucosamine does not respond

Nucleotides

• What are Nucleotides? Nucleotides are highly bio-
available nano-protein RNA and DMA factors which work
best when combined with their essential phytonutrient
synergists and co-factors.

• Nucleotide supplementation has also been shown to
improve some aspects of tissue recovery from
ischaemia/reperfusion injury or radical resection (Grimble
et al., 2001)

• Nucleotide supplements may enhance normal enterocyte
growth and maturation as well as spare the need for
exogenous glutamine in cell maintenance and
development (Chu & Walker, 2003).

Nucleotides

• In a NASA-funded research project conducted by Dr. Anil
Kulkarni at University of Texas Medical School in Houston,
nucleotides are being added to supplement the diet of
astronauts.

• “An exogenous source of NT may be particularly important
for individuals whose dietary intake of NT is low and/or
whose tissue needs are increased...” (Carver, 1995).

• "...a nucleotide supplement, given chronically may offset
the hormonal response associated with demanding
endurance exercise." (McNaughton et al., 2006)

Deer Antler Velvet

• Factors contributing to deer antler's effects in growth,
include the fact that the tissue contains many cell types
besides nutrients such as fibroblasts, chrondroblast, and
chondrocytes. Deer velvet has been shown to improve
wound healing in a like manner.

• The main glycosaminoglycan in velvet antler, chondroitin
sulfate, binds to certain proteins to form proteoglycans (as
do other lesser glycosaminoglycans [eg, decorin, keratin
sulfate, hyaluronic acid, and dermatan sulfate]). These
molecules regulate water retention and are important to
proliferate and differentiate chondrocytes. Chondrocytes
are cells that synthesize collagen and, eventually, cartilage

Proteolytic Enzymes

• These are anti-inflammatory, protein dissolving substances
which help clear the protein exudate from the injured area.

• Protease supplementation has been shown to attenuate
soft tissue injury resulting from intense exercise by
regulating leukocyte activity and inflammation

• It also helps speed up recovery from sprains, strains,
fractures, bruises, contusions, surgery and arthritis. Other
trials have shown that supplemental proteolytic enzymes
can help reduce inflammation, speed healing of bruises
and other tissue injuries (including fractures), and reduce
overall recovery time when compared to athletes taking a
placebo

Proteolytic Enzymes

• Serrapeptase has also proven invaluable in accelerating
the healing process for sprained muscles, torn ligaments
and other traumatic injuries, leg ulcers, edema as well as
post-operative inflammation.
• The mechanisms of action of serrapeptase, at the sites of
various inflammatory processes consist fundamentally of a
reduction of the exudative phenomena and an inhibition of
the release of the inflammatory mediators.
• Studies suggest that serrapeptase has a modulatory effect
on specific acute phase proteins that are involved in the
inflammatory process.

Aloe barbadensis (Aloe vera)

• The pure inner gel of the Aloe barbadensis plant contains
numerous plant phytonutrients and active components
such as saponins and polysaccharides, essential for cell
growth and renewal.

• In vivo studies have demonstrated that Aloe Vera Gel
promotes wound healing by directly stimulating the activity
of macrophages and fibroblasts. Fibroblast activation by
Aloe Vera Gel has been reported to increase both collagen
and proteoglycan synthesis, thereby promoting tissue
repair (Davis et al, 1994).

Aloe barbadensis (Aloe vera)

• Aloe Vera Gel appears to exert its anti-inflammatory
activity through bradykinase activity and thromboxane B2
and prostaglandin F2 inhibition

• Acemannan plays a significant role in the oral wound
healing process via the induction of fibroblast proliferation
and stimulation of KGF-1, VEGF, and type I collagen
expressions (Jettanacheawchankit et al., 2009).

Annatto Tocotrienol

• Annatto tocotrienol is better in the sense that it is
tocopherol-free, and hence there is no risk for interference
with benefits by alpha-tocopherol. In addition, annatto
tocotrienol provides only the most potent delta- and
gamma-tocotrienol isomers.

• Tocotrienols control inflammatory processes and markers,
including reduction of atherogenic lipoprotein(a)[Lp(a)]

• Collectively, the data suggested that tocotrienols are better
anti-inflammatory agents than α-tocopherol and the most
effective form is δ-tocotrienol (Yam et al., 2009)

Glucosamine & Chondroitin Sulfate

• Glucosamine Sulfate (GS) works by stimulating the
production of the Glycosaminoglycans (GAG) which
produce proteoglycans that hold and hydrate connective
tissue.

• GS is a major constituent of hyaluronic acid and increases
production of chondroitin sulfate in the body. GS
supplementation, therefore leads to the rehydration of
cartilage, resulting in increased lubrication and shock
absorbing capability.

Devil’s Claw (Harpagophytum Procumbens)

• Natives in the steppes of South and Southwest Africa use
the secondary root tubers of DC for the treatment of
various diseases, including musculoskeletal complaints

• It contains anti-inflammatory compounds, called iridoid
glycosides, which have been shown to possess anti-
rheumatic, analgesic, anti-arrhythmic and hypotensive
actions

• A number of animal studies have demonstrated the
antiinflammatory and analgesic effects of HP
preparations.In vitro, HP is a potent COX-2 inhibitor and
inhibits LOX, proinflammatory cytokines and elastase
(Cameron et al., 2009).

Cat’s Claw (Uncaria Tomentosa)

• A medicinal plant native to Peru, which has been used for
decades in the treatment of various inflammatory
disorders. Uncaria tomentosa (UT)can be used as an
antioxidant, has anti-apoptotic properties, and can
enhance DNA repair, however it is best know for its anti-
inflammatory properties.

• Treatment with Uncaria tomentosa extracts inhibits the
production of the pro-inflammatory cytokine, TNF-α, which
is a critical mediator of the immune response (Hall et al.,
2006)

Ecklonia Cava

• Ecklonia Cava is a seaweed. Its extract (ECe) contains
fat-soluble polyphenols and phlorotannins.

• Both Matrix metalloproteinase (MMP) expression and
activity in cells can be inhibited by EC extract. Matrix
metalloproteinase (MMP) inhibitors have been identified as
potential therapeutic candidates for metastasis, arthritis,
chronic inflammation and wrinkle formation (Kim et al.,
2006).
• Degradation of collagen and other ECM proteins is
achieved by matrix metalloproteinases (MMP). Net
collagen accumulation, however, depends not only on
increased collagen synthesis but also on decreased
degradation.

Other Helpful Agents

• Cetyl Myristoleate (CMO) This oil/fatty acid based
nutrient seems to act as a joint "lubricant" and anti-
inflammatory agent. In fact, it is patented in its use for
osteoarthritis and rheumatoid arthritis

• Hericium Erinaceus stimulation of nerve growth factor
(NGF) synthesis by hericenones from fruiting bodies and
erinacines from mycelium. Patients who receive H.
erinaceus may experience a more expeditious
improvement in the quality of life and a more complete
functional recovery after injury (Wong et al., 2011).


• Carnosine - Granulation is a tissue response with high
potential of immunity and tissue repair. Carnosine was
found to be a physiological stimulator that promotes
granulation, and as carnosine and beta-alanine were
shown to not only stimulate granulation but also accelerate
wound healing, modulate immunoresponse, and non-
specifically increase immunocompetence (Nagai & Suda,
1988).

• Since beta-alanine, the other degradation product of
carnosine, was found to stimulate the biosynthesis of
nucleic acids and collagen, histamine derived from
carnosine is considered to have enhanced the process of
wound healing by stimulating effusion at the initial stage of
inflammation.


• White Willow (Salix Alba) The role of salicylates in
inflammation and pain management is well documented in
medicine.The bark of this plant contains salicin.Following
oral administration of salicin, it was found in serum mainly
in the form of salicylic acid.

• Pharmacologically, the willow exhibits anti-inflammatory,
anti-rheumatic, antipyretic, antidotic, antigesic, and
antiseptic properties (Barnes et al., 2002).

Exogenous Nutrients for


History of Fango- & Pelotherapy

• Fangotherapy

• ‘Fango’ is an Italian word for mud.
• Thermal muds from hot springs are used for therapeutic
purposes.

• Pelotherapy

• A term historically used for mud therapies using Bentonite,
Illite (French green clay or Sea clay), or Montmorillonite
(Red desert clay).

Types of Muds/Clays

• Peat
Peat magma, a carbon matrix humate, rich in humic and
fulvic acids, delivering critical nutrients to help the body
heal itself.

• Kaolin
Kaolin Clay is high in calcium, silica, zinc and magnesium.
It also contains aluminosilicates that are known to trigger
blood clotting

• Shilajit
Shilajit, a natural mineral resin from high mountainous
areas of India, rich in key detoxifying organic acids.
contain at least 85 minerals in ionic form

How do the muds/clays work?

• Scars, traumas and adipose tissue on the body contain
toxic materials and cell wastes.

• Therapeutic clays chelate toxins that may be jamming the
electrical circuits of the body by absorbing waste through
osmotic effect.

• The mineral-rich clay provides essential nutrients
transdermally.


• Reported mechanisms of action of mud-pack therapy are
decrease in the levels of tumor necrosis factor-alpha (TNF-
α) resulting in decreased inflammatory reaction and
cartilage damage, maintenance of cartilaginous
hemostasis through decreasing serum levels of nitric oxide
and myeloperoxidases,and decrease in serum
concentrations of inflammatory mediators such as
prostaglandin E2 (PGE2) and leukotriene B4 (LTB4)
(Bellometti et al, 2002).

• “Shilajit was also found to have potent anti-inflammatory
activity in all three models of acute, sub acute and chronic
inflammation” (Suraj et al, 2007.)


• (Flusser et al, 2002) concluded that mud-pack therapy
could be used as a complementary method to
conventional therapies in knee osteoarthritis. Treatment of
knee osteoarthritis with intra-articular hyaluronic acid
injections or mud-pack therapy yielded similar results in
the short-term in terms of functional improvement and pain
relief.

Castor Oil Packs

• Two separate studies found that patients using abdominal
castor oil packs had significant increases in the production
of lymphocytes compared to those using placebo packs.
Lymphocytes are the disease-fighting cells produced by
your immune system and housed mainly in lymphatic
tissue

• When castor oil is absorbed through the skin, the flow of
lymph increases throughout the body. This speeds up the
removal of toxins surrounding the cells and reduces the
size of swollen lymph nodes. The end result is a general
overall improvement in organ function

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Notes de l'éditeur