sab basic science and partial thickness clinical slide deck

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Basic Science Rationale

• The pathogenesis of partial-thickness rotator cuff tears has been attributed to a variety of intrinsic and extrinsic causes:

– Glenohumeral instability (Davidson, et al., J Shoulder and Elbow Surg 1995)

– Subacromial impingement (Neer, J Bone Jt Surg 1972)

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– Age-related vascular changes (Lohr and Uhthoff, Clin Ortho 1990)

Courtesy S. Arnoczky

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Bey MJ, Ramsey ML, Soslowsky LJ: Intratendinous strain fields of the supraspinatus tendon:Effect of a surgically-created, articular-surface rotator cuff tear. J Shoulder Elbow Surg 11: 562-569, 2002





– Age-related vascular changes (Lohr and Uhthoff, Clin Ortho 1990)

– Differential shear stress (Bey, et al., J Shoulder Elbow Surg 2002)

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• Partial-thickness tears of the supraspinatus tendon have been shown to progress to full-thickness tears:

– 6.5% to 34.6% (Strauss, et al., Arthroscopy 2011)

– 8% (Maman, et al., J Bone Jt Surg 2009)

– 26% (Ozbaydar, et al., Acta Orthop Traumatol 2006)

– 27.5% (Yamanaka and Matsumoto, Clin Ortho 1994)

• The increase in local strain at the injury site is thought to contribute to impaired healing and tear propagation

Sano H, Wakabayashi I, Itoi E: Stress distribution in the supraspinatus tendon with partial-thicknesstears: an analysis using a two-dimensional, finite element model. J Shoulder Elbow Surg 15: 100-105, 2006

intact @ 60°


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• The increase in local strain at the injury site is thought to contribute to impaired healing and tear propagation

intact @ 60°

intact @ 60°


Sano H, Wakabayashi I, Itoi E: Stress distribution in the supraspinatus tendon with partial-thicknesstears: an analysis using a two-dimensional, finite element model. J Shoulder Elbow Surg 15: 100-105, 2006

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Basic Science Rationale: Finite Element Analysis Study

• Hypothesis Inducing a layer of new tendinous tissue on the bursal side of the supraspinatus tendon will reduce the micro-strains within the tendon, which theoretically could provide:

– Pain relief through reduced micro-motion and associated inflammation– An inhibition or arrest of tear propagation– An optimized, mechanical environment for tendon healing

• Methodology Create a two-dimensional, finite element analysis (FEA) model to determine the effect of adding 2 mm of new tendinous tissue on the intra-tendinous strain patterns that occur with bursal, articular and intra-tendinous tears

FEA model: Dr. Chen, Material and Structural Testing Core, Mayo Clinic, Rochester, MN

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Bursal surface tear

47% reduction inpeak strain

Articular surface tear

40% reduction inpeak strain

Dr. Chen, Material and Structural Testing Core, Mayo Clinic, Rochester, MN

Basic Science Rationale: Finite Element Analysis Study

The IDEAL Scaffold:• Provide a matrix scaffold to support the ingrowth of host tissues.

What are the attributes of an ideal scaffold for tissue regeneration?

• Provide a matrix scaffold to support the ingrowth of host tissues.

• Provide an inductive and conductive stimuli for cell and vessel migration.

The IDEAL Scaffold:




• Allow for normal tissue remodeling.

The IDEAL Scaffold:




• Allow for normal tissue remodeling.

• Eventually be removed by the host.

The IDEAL Scaffold:


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Scaffold Design

Van Kampen C, et al., Tissue-engineered augmentation of a rotator cuff tendon using a reconstituted collagenscaffold: A histological evaluation in sheep. Muscles, Ligaments and Tendons Journal 3:229-235, 2013.

• Highly-purified, bovine type I collagen• Highly-oriented and highly-porous (85-90%)• Minimally cross-linked and freeze-dried

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Basic Science Rationale: Pre-clinical Animal Study

Hypothesis: A custom-designed, highly-oriented, highly-porous, biocompatible, collagen implant will induce a layer of dense, regularly-oriented connective tissue when placed on the superior surface of a rotator cuff tendon in an animal (sheep) model.

Van Kampen C, et al., Tissue-engineered augmentation of a rotator cuff tendon using a reconstituted collagenscaffold: A histological evaluation in sheep. Muscles, Ligaments and Tendons Journal 3:229-235, 2013.

26 weeks12 weeks

12 weeks

T

*New tissue

When placed on the superior surface of a rotator cuff tendon (T), the implant consistently induced A layer of highly-aligned, connective tissue (*), which continued to remodel over time without evidence of an inflammatory response.

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26 weeks 26 weeks

Van Kampen C, et al, Tissue-engineered augmentation of a rotator cuff tendon using a reconstituted collagenscaffold: A histological evaluation in sheep. Muscles, Ligaments and Tendons Journal 3:229-235, 2013.


At 26 weeks, all remnants of the implant were gone and the new tissue (NT) was well-integrated into the native bone (NB). The bony insertion of the new tissue demonstrated evidence of a fibrocartilagenous (FC) component that suggests a normal, direct insertion.

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52 weeks



The histologic response demonstrated functional remodeling of the tissue at 52 weeks. The maturing tissue histologically resembled tendon-like, (dense, regularly-oriented) connective tissue. The mean thickness of the new tissue was 86% of the thickness of the underlying rotator cuff tendon.

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Key findings

• Rapid incorporation of the bioinductive implant by host tissues

• Implant stimulated both an inductive and conductive response

• Consistent production of a dense, regularly-oriented, connective tissue layer suggests functional adaptation, remodeling and maturation

• Excellent integration into bone with a fibrocartilagenous transition zone reminiscent of a normal direct insertion

• No histologic evidence of a foreign body or inflammatory response at any time for any of the animals

• Histologic response of the host remained stable at 1 year



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Basic Science Rationale: Summary

• Altered (increased) strain patterns within the supraspinatus tendon following partial-thickness tears (bursal, articular, intra-tendinous) may contribute to impaired healing, associated pain that can accompany chronic inflammation, and propagation

• FEA modeling suggests that the addition of 2 mm of new, tendinous tissue on the bursal surface of the supraspinatus tendon could reduce the peak strains created by tendon injury as much as 47% for bursal tears and 40% for articular-sided tears

• Pre-clinical animal studies confirm the ability of a highly-oriented, highly porous, biocompatible collagen scaffold to generate reproducibly a layer of dense, regularly-oriented connective tissue (histologically similar to tendon) over the surface of a rotator cuff tendon in a sheep model

• These investigations provided the basic science foundation for the first-in-man (FIM) clinical study

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Applications in Partial Thickness Cuff Lesions

Healing of partial-thickness rotator cuff tears following arthroscopic augmentation with a collagen implant:

a 2 year follow-up

Desmond J. Bokor, FRACSDavid H. Sonnabend, FRACSLuke Deady, FRANZCRBenjamin Cass, FRACSAllan A. Young, FRACSCraig L. Van Kampen, PhDSteven P. Arnoczky, DVM

Submitted for publication Journal Shoulder and Elbow Sugery

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Objective: To assess the ability of a highly porous, collagen implant to induce new tissue formation and limit tear progression when placed on the bursal surface of partial-thickness rotator cuff tears.

Hypotheses:

H1: The Rotation Medical collagen implant would induce rapid new tissue ingrowth and create an environment that would permit the functional maturation and alignment of new tendon-like tissue over the surface of the injured tendon as determined by sequential MRIs over a 24 month period.

H2: The newly induced tissue would limit tear progression of these partial-thickness lesions and prevent further degenerative changes within the tendon based on MRI evaluations.


2 yr Follow-up Bokor et al (submitted JSES)

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Patient Enrollment: (Ethics Committee approved protocol)

Inclusion Criteria:

Exclusion Criteria:

• chronic shoulder pain (˃3 months) which was resistant to analgesics, anti-inflammatory medication, and physical therapy.

• between 40-70 years of age

• recent history of steroid use• insulin-dependent diabetes• heavy smoker• genetic collagen disease• chronic inflammatory disease

• previous rotator cuff surgery• shoulder instability• grade 3 or greater chondromalacia• grade 2 or greater fatty infiltration• no sensitivity to beef products



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Patient Enrollment: 13 patients

age: 53.8 yrs averge (range 42-67) gender: 8 males, 5 females tear classification:

3 bursal sided tears: 1 high-grade, 2 intermediate-grade5 articular-sided tears: 2 high-grade, 3 intermediate-grade5 intra-substance tears: 4 high-grade, 2 intermediate-grade

MRI assessment: pre-op, 3, 6, 12, 24 months post-op

Clinical assessment: pre-op, 3, 6, 12, 24 months post-op Constant-Murley shoulder score ASES shoulder scale

Follow-up: 27 month average (range 24-32 months)



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Surgery Technique: (ask Des of Les to fill in)



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Results:

• At 3 months following surgery there was a significant (p<0.0001) increase in new tissue induction over the bursal surface of the supraspinatus tendon. (Mean thickness increase of 2.2 + 0.26 mm).



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Results:

• At 3 months following surgery there was a significant (p<0.0001) increase in new tissue induction over the bursal surface of the supraspinatus tendon. (Mean thickness increase of 2.2 + 0.26 mm).

• Over the next 9 months this increase remained stable with a progressive maturation to a more tendon-like MRI signal.



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Results:

• Pre-op MRI assessment was unable to clearly identify 3 partial lesions that were confirmed at surgery (1 bursal, 2 articular).

• Therefore, post-op MRI assessment was limited to10 patients.

• All patients demonstrated a progressive filling in of the lesions with 7 demonstrating complete disappearance of the tear.



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Results:• MRI of patients who showed progressive thickening of the tendon and improving quality of the MRI signal.



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Results:

• MRI of patients who showed progressive, albeit incomplete, healing of the tear.



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Results:

• MRI of patient demonstrating healing of high-grade, intra- substance tear over 24 months.



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Results:

• Pre-op and 12 month post-op arthroscopic appearance of a high-grade articular-sided tear demonstrating complete healing.



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Results:• Constant and ASES scores showed steady improvement

throughout the 24 month follow-up.

• A significant (p<0.01) improvement in Constant score from pre-operative values at 12 and 24 months.

• Constant pain scores demonstrated a significant (p<0.001) improvement over pre-operative scores at all time periods with significant (p=0.002) improvement between12 and 24 months.

• ASES scores showed significant (p<0.001) improvement over pre-op scores at 6, 12, and 24 months. Significant improvement

was noted between 3 and 6 months (p=0.03) and between 12 and 24 months (p=0.03).

• ASES pain scores showed significant (p<0.001) improvement over pre-op scores at all time periods.



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Summary:

• The Rotation Medical collagen implant induced significant new tissue formation in all patients by three months. This

is similar to the observation seen in the pre-clinical animal study.

• The new tissue matured over time and became indistinguishable from the underlying tendon on MRI assessment.

• The partial thickness cuff tears demonstrated complete filling of the defects in 7 patients at 12 months and a progressive improvement in the quality of the injured tendon in the other patients.

• No tear progression was observed in any of the patients at 24 months.

• All clinical scores improved significantly over time.



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Conclusion:

• The results of this clinical study demonstrate the ability of a highly porous, collagen implant to induce new tendon-like tissue formation and create an environment conductive to the healing of partial-thickness rotator cuff tears.



sab basic science and partial thickness clinical slide deck

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