Abstract
Rotator cuff tear is a common musculoskeletal disease that often requires surgical repair. Despite of recent advances in surgical techniques, the re-tear rate of the rotator cuff tendon is very high. In this study, a platelet-derived growth factor-BB (PDGF-BB)-immobilized asymmetrically porous membrane was fabricated to investigate the feasibility for enhancing rotator cuff tendon regeneration through the membrane. PDGF-BB is recognized to promote tendon regeneration. The asymmetrically porous membrane was fabricated by polycaprolactone and Pluronic F127 using an immersion precipitation technique, which can allow selective permeability (preventing scar tissue invasion into defect region but allowing permeation of oxygen/nutrients) and incorporation of bioactive molecules (e.g., PDGF-BB) via heparin binding. The PDGF-BB immobilized on the membrane was released in a sustained manner over 42 days. In an animal study using Sprague-Dawley rats, the PDGF-BB-immobilized membrane group showed significantly greater regeneration of rotator cuff tendon in histological and biomechanical analyses compared with the groups of control (suturing) and membrane without PDGF-BB immobilization. The enhancing regeneration of rotator cuff tendon of the PDGF-BB-immobilized membrane may be caused from the synergistic effect of the asymmetrically porous membrane with unique properties (selective permeability and hydrophilicity) as a scaffold for guided tendon regeneration and PDGF-BB sustainedly released from the membrane.
Similar content being viewed by others
References
Derwin KA, Badylak SF, Steinmann SP, Iannotti JP. Extracellular matrix scaffold devices for rotator cuff repair. J Shoulder Elbow Surg 2010;19:467–476.
Bedi A, Dines J, Warren RF, Dines DM. Massive tears of the rotator cuff. J Bone Joint Surg Am 2010;92:1894–1908.
Dines JS, Bedi A, ElAttrache NS, Dines DM. Single-row versus double-row rotator cuff repair:techniques and outcomes. J Am Acad Orthop Surg 2010;18:83–93.
Frank JB, El Attrache NS, Dines JS, Blackburn A, Crues J, Tibone JE. Repair site integrity after arthroscopic transosseous-equivalent suture-bridge rotator cuff repair. Am J Sports Med 2008;36:1496–1503.
Galatz LM, Ball CM, Teefey SA, Middleton WD, Yamaguchi K. The outcome and repair integrity of completely arthroscopically repaired large and massive rotator cuff tears. J Bone Joint Surg Am 2004;86-A:219–224.
Harryman DT 2nd, Mack LA, Wang KY, Jackins SE, Richardson ML, Matsen FA 3rd. Repairs of the rotator cuff. correlation of functional results with integrity of the cuff. J Bone Joint Surg Am 1991;73:982–989.
Sugaya H, Maeda K, Matsuki K, Moriishi J. Repair integrity and functional outcome after arthroscopic double-row rotator cuff repair. A prospective outcome study. J Bone Joint Surg Am 2007;89:953–960.
Jost B, Pfirrmann CW, Gerber C, Switzerland Z. Clinical outcome after structural failure of rotator cuff repairs. J Bone Joint Surg Am 2000;82:304–314.
Duquin TR, Buyea C, Bisson LJ. Which method of rotator cuff repair leads to the highest rate of structural healing? Asystematic review. Am J Sports Med 2010;38:835–841.
Kishore V, Bullock W, Sun X, Van Dyke WS, Akkus O. Tenogenic differentiation of human MSCs induced by the topography of electrochemically aligned collagen threads. Biomaterials 2012;33:2137–2144.
Chen JM, Willers C, Xu J, Wang A, Zheng MH. Autologous tenocyte therapy using porcine-derived bioscaffolds for massive rotator cuff defect in rabbits. Tissue Eng 2007;13:1479–1491.
Hee CK, Dines JS, Solchaga LA, Shah VR, Hollinger JO. Regenerative tendon and ligament healing:opportunities with recombinant human platelet-derived growth factor BB-homodimer. Tissue Eng Part B Rev 2012;18:225–234.
Dahlgren LA, van der Meulen MC, Bertram JE, Starrak GS, Nixon AJ. Insulin-like growth factor-I improves cellular and molecular aspects of healing in a collagenase-induced model of flexor tendinitis. J Orthop Res 2002;20:910–919.
Cheung EV, Silverio L, Sperling JW. Strategies in biologic augmentation of rotator cuff repair:a review. Clin Orthop Relat Res 2010;468:1476–1484.
Koh JL, Szomor Z, Murrell GA, Warren RF. Supplementation of rotator cuff repair with a bioresorbable scaffold. Am J Sports Med 2002;30:410–413.
Moffat KL, Kwei AS, Spalazzi JP, Doty SB, Levine WN, Lu HH. Novel nanofiber-based scaffold for rotator cuff repair and augmentation. Tissue Eng Part A 2009;15:115–126.
Funakoshi T, Majima T, Suenaga N, Iwasaki N, Yamane S, Minami A. Rotator cuff regeneration using chitin fabric as an acellular matrix. J Shoulder Elbow Surg 2006;15:112–118.
Ladd MR, Lee SJ, Stitzel JD, Atala A, Yoo JJ. Co-electrospun dual scaffolding system with potential for muscle-tendon junction tissue engineering. Biomaterials 2011;32:1549–1559.
Funakoshi T, Majima T, Iwasaki N, Suenaga N, Sawaguchi N, Shimode K, et al. Application of tissue engineering techniques for rotator cuff regeneration using a chitosan-based hyaluronan hybrid fiber scaffold. Am J Sports Med 2005;33:1193–1201.
Kim TH, Oh SH, Na SY, Chun SY, Lee JH. Effect of biological/physical stimulation on guided bone regeneration through asymmetrically porous membrane. J Biomed Mater Res A 2012;100:1512–1520.
Kim JR, Oh SH, Kwon GB, Namgung U, Song KS, Jeon BH, et al. Acceleration of peripheral nerve regeneration through asymmetrically porous nerve guide conduit applied with biological/physical stimulation. Tissue Eng Part A 2013;19:2674–2685.
Nevins ML, Reynolds MA. Tissue engineering with recombinant human platelet-derived growth factor BB for implant site development. Compend Contin Educ Dent 2011;32:18,20-27;quiz 28,40.
Oh SH, Kim JH, Kim JM, Lee JH. Asymmetrically porous PLGA/Pluronic F127 membrane for effective guided bone regeneration. J Biomater Sci Polym Ed 2006;17:1375–1387.
Smith PK, Mallia AK, Hermanson GT. Colorimetric method for the assay of heparin content in immobilized heparin preparations. Anal Biochem 1980;109:466–473.
Shen YH, Shoichet MS, Radisic M. Vascular endothelial growth factor immobilized in collagen scaffold promotes penetration and proliferation of endothelial cells. Acta Biomater 2008;4:477–489.
Ide J, Kikukawa K, Hirose J, Iyama K, Sakamoto H, Fujimoto T, et al. The effect of a local application of fibroblast growth factor-2 on tendon-to-bone remodeling in rats with acute injury and repair of the supraspinatus tendon. J Shoulder Elbow Surg 2009;18:391–398.
Broens L, Altena FW, Smolders CA, Koenhen DM. Asymmetric membrane structures as a result of phase separation phenomena. Desalination 1980;32:33–45.
Lustig F, Hoebeke J, Ostergren-Lundèn G, Velge-Roussel F, Bondjers G, Olsson U, et al. Alternative splicing determines the binding of platelet-derived growth factor (PDGF-AA) to glycosaminoglycans. Biochemistry 1996;35:12077–12085.
Yun YP, Yang DH, Kim SW, Park K, Ohe JY, Lee BS, et al. Local delivery of recombinant human bone morphogenic protein-2 (rhBMP-2) from rhBMP-2/heparin complex fixed to a chitosan scaffold enhances osteoblast behavior. Tissue Eng Regen Med 2014;11:163–170.
Xu X, Yu H, Gao S, Ma HQ, Leong KW, Wang S. Polyphosphoester microspheres for sustained release of biologically active nerve growth factor. Biomaterials 2002;23:3765–3772.
Kim J, Hollinger JO. Effects of dual delivery of rhPDGF-BB and rhBMP-2 on osteogenic differentiation of human mesenchymal stem cells. Tissue Eng Regen Med 2014;11:143–148.
Ide J, Kikukawa K, Hirose J, Iyama K, Sakamoto H, Mizuta H. Reconstruction of large rotator-cuff tears with acellular dermal matrix grafts in rats. J Shoulder Elbow Surg 2009;18:288–295.
Galatz LM, Sandell LJ, Rothermich SY, Das R, Mastny A, Havlioglu N, et al. Characteristics of the rat supraspinatus tendon during tendon-to-bone healing after acute injury. J Orthop Res 2006;24:541–550.
Rodeo SA, Kawamura S, Kim HJ, Dynybil C, Ying L. Tendon healing in a bone tunnel differs at the tunnel entrance versus the tunnel exit:an effect of graft-tunnel motion? Am J Sports Med 2006;34:1790–1800.
Cho NS, Yi JW, Rhee YG. Arthroscopic biceps augmentation for avoiding undue tension in repair of massive rotator cuff tears. Arthroscopy 2009;25:183–191.
Badylak SF, Tullius R, Kokini K, Shelbourne KD, Klootwyk T, Voytik SL, et al. The use of xenogeneic small intestinal submucosa as a biomaterial for Achilles tendon repair in a dog model. J Biomed Mater Res 1995;29:977–985.
Bond JL, Dopirak RM, Higgins J, Burns J, Snyder SJ. Arthroscopic replacement of massive, irreparable rotator cuff tears using a graftjacket allograft:technique and preliminary results. Arthroscopy 2008;24:403–409.e1.
Dejardin LM, Arnoczky SP, Ewers BJ, Haut RC, Clarke RB. Tissue-engineered rotator cuff tendon using porcine small intestine submucosa. Histologic and mechanical evaluation in dogs._Am J Sports Med 2001;29:175–184.
Iannotti JP, Codsi MJ, Kwon YW, Derwin K, Ciccone J, Brems JJ. Porcine small intestine submucosa augmentation of surgical repair of chronic two-tendon rotator cuff tears. A randomized, controlled trial. J Bone Joint Surg Am 2006;88:1238–1244.
Nicholson GP, Breur GJ, Van Sickle D, Yao JQ, Kim J, Blanchard CR. Evaluation of a cross-linked acellular porcine dermal patch for rotator cuff repair augmentation in an ovine model. J Shoulder Elbow Surg 2007;16(5 Suppl):S184–S190.
Santoni BG, McGilvray KC, Lyons AS, Bansal M, Turner AS, Macgillivray JD, et al. Biomechanical analysis of an ovine rotator cuff repair via porous patch augmentation in a chronic rupture model. Am J Sports Med 2010;38:679–686.
Schlegel TF, Hawkins RJ, Lewis CW, Motta T, Turner AS. The effects of augmentation with swine small intestine submucosa on tendon healing under tension:histologic and mechanical evaluations in sheep. Am J Sports Med 2006;34:275–280.
Derwin KA, Codsi MJ, Milks RA, Baker AR, McCarron JA, Iannotti JP. Rotator cuff repair augmentation in a canine model with use of a woven poly-L-lactide device. J Bone Joint Surg Am 2009;91:1159–1171.
Malcarney HL, Bonar F, Murrell GA. Early inflammatory reaction after rotator cuff repair with a porcine small intestine submucosal implant:a report of 4 cases. Am J Sports Med 2005;33:907–911.
Soler JA, Gidwani S, Curtis MJ. Early complications from the use of porcine dermal collagen implants (Permacol) as bridging constructs in the repair of massive rotator cuff tears. A report of 4 cases. Acta Orthop Belg 2007;73:432–436.
Walton JR, Bowman NK, Khatib Y, Linklater J, Murrell GA. Restore orthobiologic implant:not recommended for augmentation of rotator cuff repairs. J Bone Joint Surg Am 2007;89:786–791.
Ma PX. Scaffolds for tissue fabrication. Mater Today 2004;7:30–40.
Nair LS, Laurencin CT. Biodegradable polymers as biomaterials. Prog Polym Sci 2007;32:762–798.
Bergsma EJ, Rozema FR, Bos RR, de Bruijn WC. Foreign body reactions to resorbable poly(L-lactide) bone plates and screws used for the fixation of unstable zygomatic fractures. J Oral Maxillofac Surg 1993;51:666–670.
Ma PX, Zhang R. Synthetic nano-scale fibrous extracellular matrix. J Biomed Mater Res 1999;46:60–72.
Martin C, Winet H, Bao JY. Acidity near eroding polylactide-polyglycolide in vitro and in vivo in rabbit tibial bone chambers. Biomaterials 1996;17:2373–2380.
Oh SH, Kang SG, Lee JH. Degradation behavior of hydrophilized PLGA scaffolds prepared by melt-molding particulate-leaching method:comparison with control hydrophobic one. J Mater Sci Mater Med 2006;17:131–137.
Silva-Cunha A, Fialho SL, Naud MC, Behar-Cohen F. Poly-epsilon-caprolactone intravitreous devices:an in vivo study. Invest Ophthalmol Vis Sci 2009;50:2312–2318.
Shchmolka IR. A review of block polymer surfactants. J Am Oil Chem Soc 1977;54:110–116.
Bechgaard E, Gizurarson S, Hjortkjær RK, Sørensen AR. Intranasal administration of insulin to rabbits using glycofurol as an absorption promoter. Int J Pharmaceut 1996;128:287–289.
Kibbe AH. Handbook of pharmaceutical excipients. 3rd ed. Washington:American Pharmaceutical Association;2000.
Oh SH, Lee JY, Ghil SH, Lee SS, Yuk SH, Lee JH. PCL microparticle-dispersed PLGA solution as a potential injectable urethral bulking agent. Biomaterials 2006;27:1936–1944.
Chung YI, Tae G, Yuk SH. A facile method to prepare heparin-functionalized nanoparticles for controlled release of growth factors. Biomaterials 2006;27:2621–2626.
Yoon JJ, Chung HJ, Lee HJ, Park TG. Heparin-immobilized biodegradable scaffolds for local and sustained release of angiogenic growth factor. J Biomed Mater Res A 2006;79:934–942.
Tabata Y. The importance of drug delivery systems in tissue engineering. Pharm Sci Technol Today 2000;3:80–89.
Kobayashi M, Itoi E, Minagawa H, Miyakoshi N, Takahashi S, Tuoheti Y, et al. Expression of growth factors in the early phase of supraspinatus tendon healing in rabbits. J Shoulder Elbow Surg 2006;15:371–377.
Randelli PS, Arrigoni P, Cabitza P, Volpi P, Maffulli N. Autologous platelet rich plasma for arthroscopic rotator cuff repair. A pilot study. Disabil Rehabil 2008;30:1584–1589.
Beredjiklian PK, Favata M, Cartmell JS, Flanagan CL, Crombleholme TM, Soslowsky LJ. Regenerative versus reparative healing in tendon:a study of biomechanical and histological properties in fetal sheep. Ann Biomed Eng 2003;31:1143–1152.
Carpenter JE, Thomopoulos S, Flanagan CL, De Bano CM, Soslowsky LJ. Rotator cuff defect healing:a biomechanical and histologic analysis in an animal model. J Shoulder Elbow Surg 1998;7:599–605.
Hee CK, Dines JS, Dines DM, Roden CM, Wisner-Lynch LA, Turner AS, et al. Augmentation of a rotator cuff suture repair using rhPDGF-BB and a type I bovine collagen matrix in an ovine model. Am J Sports Med 2011;39:1630–1639.
Uggen JC, Dines J, Uggen CW, Mason JS, Razzano P, Dines D, et al. Tendon gene therapy modulates the local repair environment in the shoulder. J Am Osteopath Assoc 2005;105:20–21.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Min, H.K., Kwon, O.S., Oh, S.H. et al. Platelet-derived growth factor-BB-immobilized asymmetrically porous membrane for enhanced rotator cuff tendon healing. Tissue Eng Regen Med 13, 568–578 (2016). https://doi.org/10.1007/s13770-016-9120-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13770-016-9120-3