Augmentation of a Rotator Cuff Suture Repair Using rhPDGF-BB and a Type I Bovine Collagen Matrix in an Ovine Model

Background Rotator cuff tears are a common source of shoulder pain. High rates (20%-94%) of structural failure of the repair have been attributed to multiple factors, including poor repair tissue quality and tendon-to-bone integration. Biologic augmentation using growth factors has potential to promote tendon-to-bone integration, improving the function and long-term success of the repair. One such growth factor is platelet-derived growth factor–BB (PDGF-BB), which has been shown to improve healing in tendon and bone repair models. Hypothesis Recombinant human PDGF-BB (rhPDGF-BB) combined with a highly porous type I bovine collagen matrix will improve the biomechanical function and morphologic appearance of the repair in a dose-dependent manner, relative to a suture-only control, after 12 weeks in an acute ovine model of rotator cuff repair. Study Design Controlled laboratory study. Methods An interpositional graft consisting of rhPDGF-BB and a type I collagen matrix was implanted in an ovine model of rotator cuff repair. Biomechanical and histologic analyses were performed to determine the functional and anatomic characteristics of the repair after 12 weeks. Results A significant increase in the ultimate load to failure was observed in repairs treated with 75 μg (1490.5 ± 224.5 N, P = .029) or 150 μg (1486.6 ± 229.0 N, P = .029) of rhPDGF-BB, relative to suture-only controls (910.4 ± 156.1 N) and the 500-μg rhPDGF-BB group (677.8 ± 105.9 N). The 75-μg and 150-μg rhPDGF-BB groups also exhibited increased tendon-to-bone inter-digitation histologically. No differences in inflammation or cellularity were observed among treatments. Conclusion This study demonstrated that an interpositional graft consisting of rhPDGF-BB (75 or 150 μg) and a type I collagen matrix was able to improve the biomechanical strength and anatomic appearance in an ovine model of rotator cuff repair compared to a suture-only control and the 500-μg rhPDGF-BB group. Clinical Relevance Recombinant human PDGF-BB combined with a type I collagen matrix has potential to be used to augment surgical repair of rotator cuff tears, thereby improving clinical success.

[1]  J. Fow,et al.  The supraspinatus footprint: an anatomic study of the supraspinatus insertion. , 2004, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[2]  J. Crues,et al.  Repair Site Integrity after Arthroscopic Transosseous-Equivalent Suture-Bridge Rotator Cuff Repair , 2008, The American journal of sports medicine.

[3]  M. Olona,et al.  Surgically repaired massive rotator cuff tears: MRI of tendon integrity, muscle fatty degeneration, and muscle atrophy correlated with intraoperative and clinical findings. , 2005, AJR. American journal of roentgenology.

[4]  C Gerber,et al.  Mechanical strength of repairs of the rotator cuff. , 1994, The Journal of bone and joint surgery. British volume.

[5]  Neal S ElAttrache,et al.  Arthroscopic rotator cuff repairs: an anatomic and biomechanical rationale for different suture-anchor repair configurations. , 2007, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[6]  Orr Limpisvasti,et al.  The effect of recombinant human platelet-derived growth factor BB-coated sutures on rotator cuff healing in a sheep model. , 2010, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[7]  Richard J Hawkins,et al.  The Effects of Augmentation with Swine Small Intestine Submucosa on Tendon Healing under Tension , 2006, The American journal of sports medicine.

[8]  Kai-Nan An,et al.  Rotator cuff repair using an acellular dermal matrix graft: an in vivo study in a canine model. , 2006, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[9]  L. Qin,et al.  Supplementation-time Dependence of Growth Factors in Promoting Tendon Healing , 2006, Clinical orthopaedics and related research.

[10]  C. Puttlitz,et al.  Biomechanical Analysis of an Ovine Rotator Cuff Repair via Porous Patch Augmentation in a Chronic Rupture Model , 2010, The American journal of sports medicine.

[11]  H. Seeherman,et al.  rhBMP-12 accelerates healing of rotator cuff repairs in a sheep model. , 2008, The Journal of bone and joint surgery. American volume.

[12]  R. Hawkins,et al.  An in vivo comparison of the modified Mason-Allen suture technique versus an inclined horizontal mattress suture technique with regard to tendon-to-bone healing: a biomechanical and histologic study in sheep. , 2007, Journal of shoulder and elbow surgery.

[13]  N. Brassart,et al.  ARTHROSCOPIC REPAIR OF THE SUPRASPINATUS: DOES THE TENDON REALLY HEAL ? , 2005 .

[14]  J. Ahn,et al.  Rotator cuff integrity after arthroscopic repair for large tears with less-than-optimal footprint coverage. , 2009, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[15]  G. Breur,et al.  Evaluation of a cross-linked acellular porcine dermal patch for rotator cuff repair augmentation in an ovine model. , 2007, Journal of shoulder and elbow surgery.

[16]  A. Younger,et al.  Prospective Clinical Pilot Trial in a Single Cohort Group of rhPDGF in Foot Arthrodeses , 2010, Foot & ankle international.

[17]  Matthew J. Silva,et al.  Effect of several growth factors on canine flexor tendon fibroblast proliferation and collagen synthesis in vitro. , 2005, The Journal of hand surgery.

[18]  S L Woo,et al.  The Effects of Platelet-Derived Growth Factor-BB on Healing of the Rabbit Medial Collateral Ligament , 1998, The American journal of sports medicine.

[19]  R. Hawkins,et al.  The effect of immobilization on rotator cuff healing using modified Mason-Allen stitches: a biomechanical study in sheep. , 2001, Biomedical sciences instrumentation.

[20]  Joseph D Zuckerman,et al.  The effect of cartilage-derived morphogenetic protein 2 on initial healing of a rotator cuff defect in a rat model. , 2007, Journal of shoulder and elbow surgery.

[21]  K. An,et al.  Expression of Growth Factors in Canine Flexor Tendon After Laceration in Vivo , 2004, Annals of plastic surgery.

[22]  Matthew J. Silva,et al.  Enhanced flexor tendon healing through controlled delivery of PDGF‐BB , 2009, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[23]  C. Gerber,et al.  Experimental rotator cuff repair. A preliminary study. , 1999, The Journal of bone and joint surgery. American volume.

[24]  Louis J Soslowsky,et al.  Temporal expression of 8 growth factors in tendon-to-bone healing in a rat supraspinatus model. , 2007, Journal of shoulder and elbow surgery.

[25]  J. Tibone,et al.  Six-month magnetic resonance imaging follow-up of large and massive rotator cuff repairs reinforced with porcine small intestinal submucosa. , 2004, Journal of shoulder and elbow surgery.

[26]  James Chang,et al.  Tissue engineering of flexor tendons: optimization of tenocyte proliferation using growth factor supplementation. , 2006, Tissue engineering.

[27]  Andrew R Curran,et al.  The insertional footprint of the rotator cuff: an anatomic study. , 2006, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[28]  Umile Giuseppe Longo,et al.  Tendon augmentation grafts: a systematic review. , 2010, British medical bulletin.

[29]  S. Lynch,et al.  Recombinant human platelet-derived growth factor: biology and clinical applications. , 2008, The Journal of bone and joint surgery. American volume.

[30]  Paul Lewis,et al.  Biocompatibility of a polymer patch for rotator cuff repair , 2007, Knee Surgery, Sports Traumatology, Arthroscopy.

[31]  William D Middleton,et al.  The outcome and repair integrity of completely arthroscopically repaired large and massive rotator cuff tears. , 2004, The Journal of bone and joint surgery. American volume.

[32]  R. Warren,et al.  Platelet Rich Plasma in Rotator Cuff Repair , 2007 .

[33]  F A Matsen,et al.  Repairs of the rotator cuff. Correlation of functional results with integrity of the cuff. , 1991, The Journal of bone and joint surgery. American volume.

[34]  P. Gleyze,et al.  Functional and anatomical results after rotator cuff repair. , 1994, Clinical orthopaedics and related research.

[35]  S. Lynch,et al.  Accelerated fracture healing in the geriatric, osteoporotic rat with recombinant human platelet‐derived growth factor‐bb and an injectable beta‐tricalcium phosphate/collagen matrix , 2008, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[36]  J. Orwin,et al.  Acromial structure and tears of the rotator cuff. , 1995, Journal of shoulder and elbow surgery.

[37]  A. Turner,et al.  Experiences with sheep as an animal model for shoulder surgery: strengths and shortcomings. , 2007, Journal of shoulder and elbow surgery.

[38]  J. R. Parsons,et al.  Recombinant human platelet‐derived growth factor BB (rhPDGF‐BB) and beta‐tricalcium phosphate/collagen matrix enhance fracture healing in a diabetic rat model , 2009, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[39]  G. Genin,et al.  The development and morphogenesis of the tendon-to-bone insertion - what development can teach us about healing -. , 2010, Journal of musculoskeletal & neuronal interactions.

[40]  Matthew J. Silva,et al.  The early effects of sustained platelet-derived growth factor administration on the functional and structural properties of repaired intrasynovial flexor tendons: an in vivo biomechanic study at 3 weeks in canines. , 2007, The Journal of hand surgery.

[41]  Christian Gerber,et al.  The Results of Repair of Massive Tears of the Rotator Cuff*† , 2000, The Journal of bone and joint surgery. American volume.

[42]  R. Haut,et al.  Tissue-Engineered Rotator Cuff Tendon Using Porcine Small Intestine Submucosa , 2001, The American journal of sports medicine.

[43]  William V Giannobile,et al.  Platelet-derived growth factor stimulates bone fill and rate of attachment level gain: results of a large multicenter randomized controlled trial. , 2005, Journal of periodontology.

[44]  James S. Mason,et al.  Tendon Gene Therapy Modulates the Local Repair Environment in the Shoulder , 2005, The Journal of the American Osteopathic Association.

[45]  Matthew J. Silva,et al.  PDGF‐BB released in tendon repair using a novel delivery system promotes cell proliferation and collagen remodeling , 2007, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[46]  V. Mow,et al.  [Relationship of acromial architecture and diseases of the rotator cuff]. , 1991, Der Orthopade.

[47]  S. Bowman,et al.  The effect of growth differentiation factor-5-coated sutures on tendon repair in a rat model. , 2007, Journal of shoulder and elbow surgery.

[48]  R. Hawkins,et al.  Comparison of tunnel suture and suture anchor methods as a function of time in a sheep model. , 1999, Biomedical sciences instrumentation.

[49]  Yoichi Shimada,et al.  Expression of growth factors in the early phase of supraspinatus tendon healing in rabbits. , 2006, Journal of shoulder and elbow surgery.

[50]  Hollis G Potter,et al.  Biologic augmentation of rotator cuff tendon-healing with use of a mixture of osteoinductive growth factors. , 2007, The Journal of bone and joint surgery. American volume.

[51]  Hidetoshi Sakamoto,et al.  The effects of fibroblast growth factor-2 on rotator cuff reconstruction with acellular dermal matrix grafts. , 2009, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[52]  A. Bedi,et al.  Single‐row Versus Double‐row Rotator Cuff Repair: Techniques and Outcomes , 2010, The Journal of the American Academy of Orthopaedic Surgeons.

[53]  A. Caplan,et al.  Osteochondrogenic potential of marrow mesenchymal progenitor cells exposed to TGF‐β1 or PDGF‐BB as assayed in vivo and in vitro , 1996, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[54]  R. Gelberman,et al.  Controlled-release kinetics and biologic activity of platelet-derived growth factor-BB for use in flexor tendon repair. , 2008, The Journal of hand surgery.

[55]  R. Marx,et al.  Indications for Surgery in Clinical Outcome Studies of Rotator Cuff Repair , 2009, Clinical orthopaedics and related research.

[56]  Daniel A Grande,et al.  Tissue engineering and rotator cuff tendon healing. , 2007, Journal of shoulder and elbow surgery.

[57]  L. Dahners,et al.  Influence of dosage and timing of application of platelet‐derived growth factor on early healing of the rat medial collateral ligament , 1996, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[58]  Stephen Fealy,et al.  Biomechanical evaluation of a rotator cuff defect model augmented with a bioresorbable scaffold in goats. , 2006, Journal of shoulder and elbow surgery.

[59]  R. Gelberman,et al.  Growth factors and canine flexor tendon healing: initial studies in uninjured and repair models. , 1995, The Journal of hand surgery.