Advertisement

Allogeneic Dermal Fibroblasts Improve Tendon-to-Bone Healing in a Rabbit Model of Chronic Rotator Cuff Tear Compared With Platelet-Rich Plasma

Published:December 26, 2021DOI:https://doi.org/10.1016/j.arthro.2021.12.029

      Purpose

      To compare the effects of allogeneic dermal fibroblasts (ADFs) and platelet-rich plasma (PRP) on tendon-to-bone healing in a rabbit model of chronic rotator cuff tear.

      Methods

      Thirty-two rabbits were divided into 4 groups (8 per group). In 2 groups, the supraspinatus tendon was detached and was left as such for 6 weeks. At 6 weeks after creating the tear model, we performed transosseous repair with 5 × 106 ADFs plus fibrin injection in the left shoulder and PRP plus fibrin in the right shoulder. The relative expression of the COL1, COL3, BMP2, SCX, SOX9, and ACAN genes was assessed at 4 weeks (group A) and 12 weeks (group B) after repair. Histologic and biomechanical evaluations of tendon-to-bone healing at 12 weeks were performed with ADF injection in both shoulders in group C and PRP injection in group D.

      Results

      At 4 weeks, COL1 and BMP2 messenger RNA expression was higher in ADF-injected shoulders (1.6 ± 0.8 and 1.0 ± 0.3, respectively) than in PRP-injected shoulders (1.0 ± 0.3 and 0.6 ± 0.3, respectively) (P = .019 and P = .013, respectively); there were no differences in all genes in ADF- and PRP-injected shoulders at 12 weeks (P > .05). Collagen continuity, orientation, and maturation of the tendon-to-bone interface were better in group C than in group D (P = .024, P = .012, and P = .013, respectively) at 12 weeks, and mean load to failure was 37.4 ± 6.2 N/kg and 24.4 ± 5.2 N/kg in group C and group D, respectively (P = .015).

      Conclusions

      ADFs caused higher COL1 and BMP2 expression than PRP at 4 weeks and showed better histologic and biomechanical findings at 12 weeks after rotator cuff repair of the rabbit model. ADFs enhanced healing better than PRP in the rabbit model.

      Clinical Relevance

      This study could serve as a transitional study to show the effectiveness of ADFs in achieving tendon-to-bone healing after repair of chronic rotator cuff tears in humans.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Arthroscopy
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Mather III, R.C.
        • Koenig L.
        • Acevedo D.
        • et al.
        The societal and economic value of rotator cuff repair.
        J Bone Joint Surg Am. 2013; 95: 1993-2000
        • Chung S.W.
        • Kim J.Y.
        • Kim M.H.
        • Kim S.H.
        • Oh J.H.
        Arthroscopic repair of massive rotator cuff tears: Outcome and analysis of factors associated with healing failure or poor postoperative function.
        Am J Sports Med. 2013; 41: 1674-1683
        • Sugaya H.
        • Maeda K.
        • Matsuki K.
        • Moriishi J.
        Functional and structural outcome after arthroscopic full-thickness rotator cuff repair: Single-row versus dual-row fixation.
        Arthroscopy. 2005; 21: 1307-1316
        • Park J.G.
        • Cho N.S.
        • Song J.H.
        • Baek J.H.
        • Jeong H.Y.
        • Rhee Y.G.
        Rotator cuff repair in patients over 75 years of age: Clinical outcome and repair integrity.
        Clin Orthop Surg. 2016; 8: 420-427
        • Oh J.H.
        • Park M.S.
        • Rhee S.M.
        Treatment strategy for irreparable rotator cuff tears.
        Clin Orthop Surg. 2018; 10: 119-134
        • Ruiz-Moneo P.
        • Molano-Muñoz J.
        • Prieto E.
        • Algorta J.
        Plasma rich in growth factors in arthroscopic rotator cuff repair: A randomized, double-blind, controlled clinical trial.
        Arthroscopy. 2013; 29: 2-9
        • Sánchez M.
        • Anitua E.
        • Delgado D.
        • et al.
        Platelet-rich plasma, a source of autologous growth factors and biomimetic scaffold for peripheral nerve regeneration.
        Expert Opin Biol Ther. 2017; 17: 197-212
        • Han C.
        • Na Y.
        • Zhu Y.
        • et al.
        Is platelet-rich plasma an ideal biomaterial for arthroscopic rotator cuff repair? A systematic review and meta-analysis of randomized controlled trials.
        J Orthop Surg Res. 2019; 14: 183
        • Chung S.W.
        • Song B.W.
        • Kim Y.H.
        • Park K.U.
        • Oh J.H.
        Effect of platelet-rich plasma and porcine dermal collagen graft augmentation for rotator cuff healing in a rabbit model.
        Am J Sports Med. 2013; 41: 2909-2918
        • Jo C.H.
        • Shin J.S.
        • Shin W.H.
        • Lee S.Y.
        • Yoon K.S.
        • Shin S.
        Platelet-rich plasma for arthroscopic repair of medium to large rotator cuff tears: A randomized controlled trial.
        Am J Sports Med. 2015; 43: 2102-2110
        • Pandey V.
        • Bandi A.
        • Madi S.
        • et al.
        Does application of moderately concentrated platelet-rich plasma improve clinical and structural outcome after arthroscopic repair of medium-sized to large rotator cuff tear? A randomized controlled trial.
        J Shoulder Elbow Surg. 2016; 25: 1312-1322
        • Kim D.H.
        • Kim S.H.
        Platelet-rich plasma in arthroscopic rotator cuff repair.
        Clin Shoulder Elbow. 2015; 18: 113-118
        • Zhao J.G.
        • Zhao L.
        • Jiang Y.X.
        • Wang Z.L.
        • Wang J.
        • Zhang P.
        Platelet-rich plasma in arthroscopic rotator cuff repair: A meta-analysis of randomized controlled trials.
        Arthroscopy. 2015; 31: 125-135
        • Fu C.J.
        • Sun J.B.
        • Bi Z.G.
        • Wang X.M.
        • Yang C.L.
        Evaluation of platelet-rich plasma and fibrin matrix to assist in healing and repair of rotator cuff injuries: A systematic review and meta-analysis.
        Clin Rehabil. 2017; 31: 158-172
        • Cai Y.Z.
        • Zhang C.
        • Lin X.J.
        Efficacy of platelet-rich plasma in arthroscopic repair of full-thickness rotator cuff tears: A meta-analysis.
        J Shoulder Elbow Surg. 2015; 24: 1852-1859
        • Barber F.A.
        PRP as an adjunct to rotator cuff tendon repair.
        Sports Med Arthrosc Rev. 2018; 26: 42-47
        • Saltzman B.M.
        • Jain A.
        • Campbell K.A.
        • et al.
        Does the use of platelet-rich plasma at the time of surgery improve clinical outcomes in arthroscopic rotator cuff repair when compared with control cohorts? A systematic review of meta-analyses.
        Arthroscopy. 2016; 32: 906-918
        • Rodeo S.A.
        • Delos D.
        • Williams R.J.
        • Adler R.S.
        • Pearle A.
        • Warren R.F.
        The effect of platelet-rich fibrin matrix on rotator cuff tendon healing: A prospective, randomized clinical study.
        Am J Sports Med. 2012; 40: 1234-1241
        • Schwitzguebel A.J.
        • Kolo F.C.
        • Tirefort J.
        • Saffarini M.
        • Lädermann A.
        Efficacy of platelet-rich plasma for the treatment of interstitial supraspinatus tears: Response.
        Am J Sports Med. 2020; 48: NP9-NP10
        • Schwitzguebel A.J.
        • Kolo F.C.
        • Tirefort J.
        • et al.
        Efficacy of platelet-rich plasma for the treatment of interstitial supraspinatus tears: A double-blinded, randomized controlled trial.
        Am J Sports Med. 2019; 47: 1885-1892
        • Lee C.H.
        • Shah B.
        • Moioli E.K.
        • Mao J.J.
        CTGF directs fibroblast differentiation from human mesenchymal stem/stromal cells and defines connective tissue healing in a rodent injury model.
        J Clin Invest. 2015; 125: 3992
        • Bainbridge P.
        Wound healing and the role of fibroblasts.
        J Wound Care. 2013; 22 (410-412): 407-408
        • Kwon J.
        • Kim Y.H.
        • Rhee S.M.
        • et al.
        Effects of allogenic dermal fibroblasts on rotator cuff healing in a rabbit model of chronic tear.
        Am J Sports Med. 2018; 46: 1901-1908
        • Liu W.
        • Chen B.
        • Deng D.
        • Xu F.
        • Cui L.
        • Cao Y.
        Repair of tendon defect with dermal fibroblast engineered tendon in a porcine model.
        Tissue Eng. 2006; 12: 775-788
        • Sandulache V.C.
        • Zhou Z.
        • Sherman A.
        • Dohar J.E.
        • Hebda P.A.
        Impact of transplanted fibroblasts on rabbit skin wounds.
        Arch Otolaryngol Head Neck Surg. 2003; 129: 345-350
        • Mazlyzam A.L.
        • Aminuddin B.S.
        • Saim L.
        • Ruszymah B.H.
        Human serum is an advantageous supplement for human dermal fibroblast expansion: Clinical implications for tissue engineering of skin.
        Arch Med Res. 2008; 39: 743-752
        • Bei Y.
        • Zhou Q.
        • Fu S.
        • et al.
        Cardiac telocytes and fibroblasts in primary culture: Different morphologies and immunophenotypes.
        PLoS One. 2015; 10e0115991
        • Lee J.H.
        • Kim Y.H.
        • Rhee S.M.
        • et al.
        Rotator cuff tendon healing using human dermal fibroblasts: Histological and biomechanical analyses in a rabbit model of chronic rotator cuff tears.
        Am J Sports Med. 2021; (3635465211041102)
        • Chung S.W.
        • Park H.
        • Kwon J.
        • Choe G.Y.
        • Kim S.H.
        • Oh J.H.
        Effect of hypercholesterolemia on fatty infiltration and quality of tendon-to-bone healing in a rabbit model of a chronic rotator cuff tear: Electrophysiological, biomechanical, and histological analyses.
        Am J Sports Med. 2016; 44: 1153-1164
        • Zhou Y.
        • Zhang J.
        • Wu H.
        • Hogan M.V.
        • Wang J.H.
        The differential effects of leukocyte-containing and pure platelet-rich plasma (PRP) on tendon stem/progenitor cells—Implications of PRP application for the clinical treatment of tendon injuries.
        Stem Cell Res Ther. 2015; 6: 173
        • Oh J.H.
        • Kim W.
        • Park K.U.
        • Roh Y.H.
        Comparison of the cellular composition and cytokine-release kinetics of various platelet-rich plasma preparations.
        Am J Sports Med. 2015; 43: 3062-3070
        • Gwinner C.
        • Gerhardt C.
        • Haneveld H.
        • Scheibel M.
        Two-staged application of PRP in arthroscopic rotator cuff repair: A matched-pair analysis.
        Arch Orthop Trauma Surg. 2016; 136: 1165-1171
        • Cavallo C.
        • Roffi A.
        • Grigolo B.
        • et al.
        Platelet-rich plasma: The choice of activation method affects the release of bioactive molecules.
        Biomed Res Int. 2016; 2016: 6591717
        • Hurley E.T.
        • Lim Fat D.
        • Moran C.J.
        • Mullett H.
        The efficacy of platelet-rich plasma and platelet-rich fibrin in arthroscopic rotator cuff repair: A meta-analysis of randomized controlled trials.
        Am J Sports Med. 2019; 47: 753-761
        • Oh J.H.
        • Chung S.W.
        • Kim S.H.
        • Chung J.Y.
        • Kim J.Y.
        2013 Neer Award: Effect of the adipose-derived stem cell for the improvement of fatty degeneration and rotator cuff healing in rabbit model.
        J Shoulder Elbow Surg. 2014; 23: 445-455
        • Kim Y.S.
        • Sung C.H.
        • Chung S.H.
        • Kwak S.J.
        • Koh Y.G.
        Does an injection of adipose-derived mesenchymal stem cells loaded in fibrin glue influence rotator cuff repair outcomes? A clinical and magnetic resonance imaging study.
        Am J Sports Med. 2017; 45: 2010-2018
        • Lui P.P.
        Stem cell technology for tendon regeneration: Current status, challenges, and future research directions.
        Stem Cells Cloning. 2015; 8: 163-174
        • Clarke A.W.
        • Alyas F.
        • Morris T.
        • Robertson C.J.
        • Bell J.
        • Connell D.A.
        Skin-derived tenocyte-like cells for the treatment of patellar tendinopathy.
        Am J Sports Med. 2011; 39: 614-623
        • Connell D.
        • Datir A.
        • Alyas F.
        • Curtis M.
        Treatment of lateral epicondylitis using skin-derived tenocyte-like cells.
        Br J Sports Med. 2009; 43: 293-298
        • Kajikawa Y.
        • Morihara T.
        • Sakamoto H.
        • et al.
        Platelet-rich plasma enhances the initial mobilization of circulation-derived cells for tendon healing.
        J Cell Physiol. 2008; 215: 837-845
        • Ho J.O.
        • Sawadkar P.
        • Mudera V.
        A review on the use of cell therapy in the treatment of tendon disease and injuries.
        J Tissue Eng. 2014; 5 (2041731414549678)
        • Suh D.S.
        • Lee J.K.
        • Yoo J.C.
        • et al.
        Atelocollagen enhances the healing of rotator cuff tendon in rabbit model.
        Am J Sports Med. 2017; 45: 2019-2027
        • Maffulli N.
        • Moller H.D.
        • Evans C.H.
        Tendon healing: Can it be optimised?.
        Br J Sports Med. 2002; 36: 315-316
        • Rodeo S.A.
        • Potter H.G.
        • Kawamura S.
        • Turner A.S.
        • Kim H.J.
        • Atkinson B.L.
        Biologic augmentation of rotator cuff tendon-healing with use of a mixture of osteoinductive growth factors.
        J Bone Joint Surg Am. 2007; 89: 2485-2497
        • St Pierre P.
        • Olson E.J.
        • Elliott J.J.
        • O'Hair K.C.
        • McKinney L.A.
        • Ryan J.
        Tendon-healing to cortical bone compared with healing to a cancellous trough. A biomechanical and histological evaluation in goats.
        J Bone Joint Surg Am. 1995; 77: 1858-1866
        • Uhthoff H.K.
        • Sano H.
        • Trudel G.
        • Ishii H.
        Early reactions after reimplantation of the tendon of supraspinatus into bone. A study in rabbits.
        J Bone Joint Surg Br. 2000; 82: 1072-1076
        • Oryan A.
        • Alidadi S.
        • Moshiri A.
        • Bigham-Sadegh A.
        Bone morphogenetic proteins: A powerful osteoinductive compound with non-negligible side effects and limitations.
        Biofactors. 2014; 40: 459-481
        • Yang L.
        • Yamasaki K.
        • Shirakata Y.
        • et al.
        Bone morphogenetic protein-2 modulates Wnt and frizzled expression and enhances the canonical pathway of Wnt signaling in normal keratinocytes.
        J Dermatol Sci. 2006; 42: 111-119
        • Krishnan V.
        • Bryant H.U.
        • Macdougald O.A.
        Regulation of bone mass by Wnt signaling.
        J Clin Invest. 2006; 116: 1202-1209
        • Driskell R.R.
        • Watt F.M.
        Understanding fibroblast heterogeneity in the skin.
        Trends Cell Biol. 2015; 25: 92-99
        • Liang P.
        • Huang X.
        • Jian B.
        • et al.
        Bone morphogenetic protein 2 is involved in the proliferation and collagen synthesis of human hyperplastic scar fibroblasts.
        Int J Clin Exp Med. 2016; 9: 13926-13933
        • Shan J.
        • Wang I.
        • Lu H.
        Osteoblast-fibroblast interactions modulate cell phenotypes through paracrine and autocrine regulations.
        Trans Orthop Res Soc. 2007; 32: 30
        • Oztermeli A.
        • Karaca S.
        • Yucel I.
        • Midi A.
        • Sen E.I.
        • Ozturk B.Y.
        The effect of erythropoietin on rat rotator cuff repair model: An experimental study.
        J Orthop Surg (Hong Kong). 2019; 27 (2309499019856389)