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Josh Hackel MDAndrews Institute

Orthobiologics and

Musculoskeletal Ultrasound in Sports Medicine � Discuss orthobiologics:

popular treatment options available

� Musculoskeletal Ultrasound◦ Diagnostic and therapeutic uses in sports medicine

� Platelet Rich Plasma (PRP)

� Bone Marrow derived stem cells

� Adipose derived stem cells

� Placental derived growth factors and stem cells

� Engineering of tissue in vitro for subsequent

� implantation in vivo

� OR

� Regeneration of tissue directly in vivo.

� Problem: One of the main issues with tissue healing is that the tissue heals via reactive scar formation instead of truly regenerating new tissue

� Goal: improve the biological environment around the defect to create the best possible healing situations and improve healing response

� Action: biologic manipulation of the healing milieu will play a critical role in the improvement of the healing rate

Fat (adipose tissue)Fat (adipose tissue)

Bone MarrowBone Marrow

Blood (PRP & stem cells)Blood (PRP & stem cells)

Prenatal (Amniotic Tissue)Prenatal (Amniotic Tissue)

Autologous

Allogeneic

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� Type of injection therapy usedinjection therapy usedinjection therapy usedinjection therapy used for various chronic sports injuries to promote healing.

� PRP = abbreviation for Platelet-Rich Plasma.

� Over 6,000 PRP journal articles have been published between 2013-15 (between 2012-13 was about 400).

The “modern” version of dextrose prolotherapy: Injections of autologous centrifuged blood with platelets concentrated is used as the injectate.

Marx and Garg. Dental and Craniofascial applications of Platelet Rich Plasma.

Quintessence Publishing Co., Inc. 2005

Normal Blood Platelet Rich Plasma

� First human application was described in mandibular reconstruction in oromaxillarysurgery in 1998 (Robert Marx, Prof. of Surgery and Chief of Oromaxillary

Surgery Division at Univ. of Miami).� Since then, PRP has experienced a surge in

clinical uses and research.� Endorsement from athletes.◦ Tiger Woods ◦ Alex Rodriguez (NY Yankees)◦ Masahiro Tanaka (NY Yankees)◦ Kobe Bryant (LA Lakers)◦ Troy Polamalu (Pitts Steelers)◦ Hines Ward (Pitts Steelers, 2009)

� From web, Charlottesville Orthopedic Center PLC

� Think of:

� PRP as ”Fertilizer”

� Stem Cells as ”Seeds”

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ADIPOSE TISSUEADIPOSE TISSUEADIPOSE TISSUEADIPOSE TISSUE

(Zuk et al. 2001)(Zuk et al. 2001)(Zuk et al. 2001)(Zuk et al. 2001)

and

BONE MARROWBONE MARROWBONE MARROWBONE MARROW

(Caplan et al. 1991)(Caplan et al. 1991)(Caplan et al. 1991)(Caplan et al. 1991)

andandandand

Peripheral BloodPeripheral BloodPeripheral BloodPeripheral Blood

(Saw et al.)(Saw et al.)(Saw et al.)(Saw et al.)

� First identified in bone marrow bone marrow bone marrow bone marrow by Caplan in 1991 and, subsequently, in adipose tissues adipose tissues adipose tissues adipose tissues by Zuk et al at UCLA in 2001, Mesenchymal Adult Stem Cells now know as Medicinal Secreting Cells can differentiate into:

◦ Ligament◦ Tendon◦ Cartilage◦ Muscle◦ Bone◦ Adipose tissue

Courtesy of Donna Alderman, D.O.

� Not entirely understood.

� 1) Regeneration of cartilage has been demonstrated in vitro and in animal models.

(Agung et al. Knee Surg, 2006)

� 2) Paracrine mechanism (cell-to-cell talk) via cytokines and growth factors.

(Bunnell et al. Cell Res and Therapy 2010)

� In US, however, FDA FDA FDA FDA does not does not does not does not allow culturing of the allow culturing of the allow culturing of the allow culturing of the stem cells stem cells stem cells stem cells in clinics.

(FDA does not allow these cells to be “more than minimally manipulated” or be outside of the patient for over 24 hrs.)

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Bone Marrow Aspiration & Centrifugation.

• Minimally invasive harvest

• Adipose tissue is known to contain properties that may aid in healing and tissue repair

• High concentrations of reparative elements found within adipose tissue

o 100 to 500 times more reparative 100 to 500 times more reparative 100 to 500 times more reparative 100 to 500 times more reparative cells than from an equivalent cells than from an equivalent cells than from an equivalent cells than from an equivalent amount of bone marrowamount of bone marrowamount of bone marrowamount of bone marrow2 (these cells

in adipose tissue are unlikely to decrease

with age, as with bone marrow)

• Almost everyone is happy to donate fat

2Hass, Ralf, Cornelia Kasper, Stefanie Böhm, and Roland Jacobs. "Different Populations and Sources of Human Mesenchymal Stem Cells (MSC): A Comparison of Adult and Neonatal Tissue-derived MSC." Cell Commun Signal Cell Communication and Signaling 9.1 (2011): 12.

Collect lipoaspirate: approximately 3-4x final desired volume of Lipogems

Perivascular cells reside on very tiny blood vessels. These micro-sized blood vessels are HIGHLY concentrated in fat

Adipose tissue (fat)

Perivascular cells on micro-capillaries

• Perivascular cells are a type of cell that is wrapped around small blood vessels within adipose tissue.

• It is known to react to a site of injury and promote a reparative environment.

• The natural repair mechanism occurs by communicating with local tissues to aid in healing.

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PERICY

TEMS

C

ACTIVATE

D

MSC

Proposed Sequence of Change Due to Injury:

Arnold Caplan, PhD (2013)

TROPHIC EFFECTS = secreted bioactive molecules (like mini drugstores)

Arnold Caplan, PhD (2013)

�Many proprietary companies

�Most are derived from allograft placental tissue typically amniotic layer

�Logistically a prepackaged simple allograft tissue injection

� Release of growth factors

� Stimulation of growth factor production

� Promote mesenchymal stem cell migration

� Recruits circulating hematopoietic stem cells

� Contains angiogenic growth factors

AC joint separation

Achilles tendonitisAchilles tendinosis

Achilles tendon ruptureACL repair – BTJ

healingAnkle sprain (high)Bone-Tendon junction

(BTJ) healing diseases

ConcussionChronic traumatic

encephalopathy

(CTE)Chronic bursitis

Dislocations (shoulder)Epicondylitis

FracturesHamstring injury

Low back strain

Meniscus injury (knee)MCL injuries

Muscle injuriesNerve injuriesOsteoarthritis

Plantar fasciitisRotator cuff tears

Side stitchShin splintsSpinal cord injury

Stress FracturesTendinitis

Tennis elbowTurf toe

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�Small or large peripheral joints

� Insures precision

�No “fishing around”

�Ability to document procedures

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� Therapeutic Interventions◦ aspiration cyst/ bursal / hematoma / soft calcification◦ Difficult joint injections

� Small joints, hip injections◦ Tendon sheath injections

� Biceps, paratenon of achilles, deQuervein’s◦ Regenerative tendon injections

� Prolotherapy� PRP injections� Stem cell injections◦ Nerve entrapments associated with soft tissue injury

� hydrodissection◦ Releases/ Tenotomy with Tenex FAST procedure

� Lateral elbow� Plantar fascia� Trigger digit

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• Dynamic Real time

patient interaction

• Soft tissue

• Better spatial resolution

• No radiation

• No contraindications

• Low cost

Ideal for diagnostics & therapeutic injections

Why Musculoskeletal Ultrasound?

SHORT AXIS LONG AXIS

Hypoechoic Defect full

thickness rotator cuff tear

NTS

FLUID AROUND THE LONG BICEPS TENDON

Short Axis Long Axis

Intra-articular

SASD anterior recess

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148 painful joints IA triamcinolone acetonide injection by palpation-guided injection or US guided injection

43% reduced procedural pain

58.5% reduction in absolute pain

scores (p < 0.001)

75% reduction in significant pain

(VAS p < 0.001)

US also increased detection of

effusion by 200% , volume of

aspirated fluid by 337%

CMC Joint injection

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A randomized comparative study of short term response to blind injection versus sonographic-guided injection of local corticosteroids in patients with painful shoulder.

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41 patients with painful shoulder

Group 1 blind subacromial injection of 20 mg triamcinolone (n =20)Group 2 US guided injection of 20 mg triamcinolone (n = 21)

assessed within 5 days before injection & 6 weeks after injection

Six weeks after injection, the VAS and the SFA score showed a

significantly greater improvement in Group 2 compared withGroup 1 (mean VAS score change 34.9 for Group 2 vs 7.1 for

Group 1, p < 0.001 42

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4344

◦ Joint space is often collapsed and Joint space is often collapsed and Joint space is often collapsed and Joint space is often collapsed and indistinguishableindistinguishableindistinguishableindistinguishable

◦ Arthroscopy: The Journal of Arthroscopy: The Journal of Arthroscopy: The Journal of Arthroscopy: The Journal of Arthroscopic & Related SurgeryArthroscopic & Related SurgeryArthroscopic & Related SurgeryArthroscopic & Related Surgery, El , El , El , El

Attrache Attrache Attrache Attrache ‘‘‘‘05050505

(41 live awake patients injected (41 live awake patients injected (41 live awake patients injected (41 live awake patients injected anteriorly)anteriorly)anteriorly)anteriorly)

Only 26.8% (11 of 41) of injections placed anteriorly were actually intra-articular

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� 40 cadaver shoulders injected, 20 anteriorly and 20 posteriorly, to assess the accuracy of injections placed in the glenohumeral joint

� 1 mL gadolinium injected into the joint to determine accuracy of position

� The anterior approach had an 80% accuracy rate and .75 positive predictive value

� The posterior approach had a 50% accuracy rate and a .67 positive predictive value.

� Anterior injections produced higher rate of accuracy than posterior injections.

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Glenohumeral Joint injection

medial to lateralapproach LAX

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Glenohumeral Joint inj medial to lateral approach

LAX

GH jt lateral to medial approach

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Twenty-eight consecutive patients

Overall, 97% of US guided

needles were accurate.

1 inaccurate placement from inadvertent needle

withdrawal during connection of the

extension tubing for contrast agent injection

Conclusions: US guidance

can be used to inject the native adult hip joint with

acceptable accuracy

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� 40 patients with hip OA and synovitis detected by US

� 40 IA steroid injection under US guidance compared to age matched controls

� Walking pain VAS reduced vs baseline P<0.001 at 1 & 3 months

� Synovial hypertrophy reduced in 75% at 1 & 3 months vs baseline

� Conclusion: efficacious, safe therapeutic approach for pain control and reducing synovial hypertrophy avoiding use of X-ray guidance

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� 12121212 US-guided and 12121212 unguided pes anserinus bursa injections

� 92% (11 of 12 specimens) in the US-guided

� 17% (2 of 12 specimens) in the unguided

� US-guided injection technique was significantly more accurate than the unguided technique (Williams-corrected chi(2) = 12.528, P < .01).

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AccuracyAccuracyAccuracyAccuracy ofofofof ultrasoundgultrasoundgultrasoundgultrasoundguideduideduideduided versusversusversusversus palpationpalpationpalpationpalpation----guidedguidedguidedguided acromioclavicular acromioclavicular acromioclavicular acromioclavicular jointjointjointjoint injections: a injections: a injections: a injections: a cadaveric studycadaveric studycadaveric studycadaveric study

10 US guided and 10 palpation-

guided ACJ injections

All 10 US guided (100%) injected into ACJ

4 of 10 (40%) palpation-

guided injections within the ACJ (P = .0054)

Is bigger better???

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� Hand held Ultrasound devices

FAST

ProcedureFocused

assessment

with sonography

for trauma

� Regenerative Medicine for MSK application is still

in its infancy as a therapeutic agent yet will likely

be a prominent part of the future orthopaedic

landscape

� It appears promising and safe, offering an exciting

alternative to chronic injuries unresponsive to

conventional treatments as well as acute partial

tears and chondral injuries.

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� U/S is a useful tool in guiding minimally invasive orthobiologicprocedures

� New and exciting modality that will assist in better diagnosing and treating sports medicine conditions in the training room, sideline, or in your clinic

� The field is still emerging and expertise takes time and practice

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Hands-On Diagnostic and

Interventional MSK US Course

June 8-11, 2017

Go to our website Andrewsref.org

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Thank You!

Joshua.hackel@bhcpns.org

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