Effect of microfracture combined with biomimetic hydrogel scaffold on rotator cuff tendon-to-bone healing in rabbits_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

HUANG Chenglong ¹ , ZHAO Song ² ,  CHENG Biao ¹ , CHEN Gang ³ , PAN Jieen ³

1. Department of Orthopedics, Clinical Medical School, the Affiliated Shanghai No.10 People’s Hospital, Nanjing Medical University, Shanghai, 200072, P.R.China;
2. Department of Sports Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, P.R.China;
3. Department of Orthopaedics, the Second Affiliated Hospital of Jiaxing University, Jiaxing Zhejiang, 314000, P.R.China;

Corresponding?author：

CHENG Biao, Email: 13681973702@sina.cn

Keywords：

Rotator cuff tear; microfracture; hydrogel; tendon-to-bone healing; rabbit

DOI：

10.7507/1002-1892.202001029

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Objective To assess the effect of microfracture and biomimetic hydrogel scaffold on tendon-to-bone healing in a rabbit rotator cuff tear model.Methods Gelatin and methacrylic anhydride were used to synthesize gelatin methacryloyl (GelMA). Then the GelMA were treated with ultraviolet rays and vacuum freeze-drying method to obtain a biomimetic hydrogel scaffold. The morphology of the scaffold was observed by gross observation and scanning electron microscope. Degradation of the scaffold was determined at different time points. Twenty-four adult New Zealand rabbits, weighting 2.8-3.5 kg and male or female, were surgically created the bilateral acute rotator cuff tear models. One shoulder was treated with microfractures on the footprint and transosseous suture (control group, n=24). The other shoulder was treated with the same way, except for putting the scaffold on the footprint before transosseous suture (experimental group, n=24). The general conditions of rabbits were observed postoperatively. Tendon-to-bone healing was evaluated by gross observation, Micro-CT, HE staining, and bio-mechanical testing at 4 and 8 weeks after operation.Results The scaffold was white and has a porous structure with pore size of 31.7-89.9 μm, which degraded slowly in PBS solution. The degradation rate was about 95% at 18 days. All the rabbits survived to the completion of the experiment. Micro-CT showed that there was no obvious defect and re-tear at the tendon-to-bone interface in both groups. No difference was found in bone mineral density (BMD), tissue mineral density (TMD), and bone volume/total volume (BV/TV) between the two groups at 4 and 8 weeks postoperatively (P>0.05). HE staining showed that the fibrous scar tissue was the main component at the tendon-to-bone interface in the control group at 4 and 8 weeks postoperatively; the disorderly arranged mineralized cartilage and fibrocartilage formation were observed at the tendon-to-bone interface in the experimental group at 4 weeks, and the orderly arranged cartilage formation was observed at 8 weeks. Besides, the tendon maturation scores of the experimental group were significantly higher than those of the control group at 4 and 8 weeks (P<0.05). There was no significant difference in the ultimate load to failure and stiffness between the two groups at 4 weeks (P>0.05); the ultimate load to failure at 8 weeks was significantly higher in the experiment group than in the control group (t=4.162, P=0.009), and no significant difference was found in stiffness between the two groups at 8 weeks (t=2.286, P=0.071).Conclusion Compared with microfracture alone, microfracture combined with biomimetic hydrogel scaffold can enhance tendon-to-bone healing and improve the ultimate load to failure in rabbits.

Citation： HUANG Chenglong, ZHAO Song, CHENG Biao, CHEN Gang, PAN Jieen. Effect of microfracture combined with biomimetic hydrogel scaffold on rotator cuff tendon-to-bone healing in rabbits. Chinese Journal of Reparative and Reconstructive Surgery, 2020, 34(9): 1177-1183. doi: 10.7507/1002-1892.202001029 Copy

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2.	Li X, Cheng R, Sun Z, et al. Flexible bipolar nanofibrous membranes for improving gradient microstructure in tendon-to-bone healing. Acta Biomater, 2017, 61: 204-216.
3.	Tsekes D, Konstantopoulos G, Khan WS, et al. Use of stem cells and growth factors in rotator cuff tendon repair. Eur J Orthop Surg Traumatol, 2019, 29(4): 747-757.
4.	潘娟, 劉國明, 寧良菊, 等. 脫細胞肌腱片促進兔肩袖損傷腱-骨愈合的實驗研究. 中國修復重建外科雜志, 2013, 27(9): 1070-1075.
5.	He P, Ng KS, Toh SL, et al. In vitro ligament-bone interface regeneration using a trilineage coculture system on a hybrid silk scaffold. Biomacromolecules, 2012, 13(9): 2692-2703.
6.	Sanzenbacher R, Dwenger A, Schuessler-Lenz M, et al. European regulation tackles tissue engineering. Nat Biotechnol, 2007, 25(10): 1089-1091.
7.	Min HK, Oh SH, Lee JM, et al. Porous membrane with reverse gradients of PDGF-BB and BMP-2 for tendon-to-bone repair: in vitro evaluation on adipose-derived stem cell differentiation. Acta Biomater, 2014, 10(3): 1272-1279.
8.	Narayanan G, Nair LS, Laurencin CT. Regenerative engineering of the rotator cuff of the shoulder. ACS Biomaterials Science & Engineering, 2018, 4(3): 751-786.
9.	高超, 李超明, 徐玉龍, 等. 靜電紡絲聚己內酯/Ⅰ型膠原納米纖維取向性補片用于肩袖修復. 中國修復重建外科雜志, 2019, 33(5): 628-633.
10.	Zhu Q, Ma Z, Li H, et al. Enhancement of rotator cuff tendon-bone healing using combined aligned electrospun fibrous membranes and kartogenin. RSC Advances, 2019, 9(27): 15582-15592.
11.	Bilsel K, Yildiz F, Kapicioglu M, et al. Efficacy of bone marrow-stimulating technique in rotator cuff repair. J Shoulder Elbow Surg, 2017, 26(8): 1360-1366.
12.	Kon E, Filardo G, Perdisa F, et al. Acellular matrix-based cartilage regeneration techniques for osteochondral repair. Operative Techniques in Orthopaedics, 2014, 24(1): 14-18.
13.	Degirmenci E, Ozturan KE, Sahin AA, et al. Effects of tranexamic acid on the recovery of osteochondral defects treated by microfracture and acellular matrix scaffold: an experimental study. J Orthop Surg Res, 2019, 14(1): 105.
14.	馬潞, 田猛. 可注射明膠原位水凝膠作為脫鈣骨基質粉末輸送載體可行性的初步研究. 中國修復重建外科雜志, 2017, 31(3): 300-305.
15.	Yue K, Trujillo-de Santiago G, Alvarez MM, et al. Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels. Biomaterials, 2015, 73: 254-271.
16.	Van Den Bulcke AI, Bogdanov B, De Rooze N, et al. Structural and rheological properties of methacrylamide modified gelatin hydrogels. Biomacromolecules, 2000, 1(1): 31-38.
17.	Ide J, Kikukawa K, Hirose J, et al. Reconstruction of large rotator-cuff tears with acellular dermal matrix grafts in rats. J Shoulder Elbow Surg, 2009, 18(2): 288-295.
18.	Font Tellado S, Balmayor ER, Van Griensven M. Strategies to engineer tendon/ligament-to-bone interface: Biomaterials, cells and growth factors. Adv Drug Deliv Rev, 2015, 94: 126-140.
19.	費文勇, 郭衛春. 成體干細胞技術促肩袖損傷修復實驗研究進展. 國際骨科學雜志, 2015, 36(1): 45-48.
20.	Rothrauff BB, Tuan RS. Cellular therapy in bone-tendon interface regeneration. Organogenesis, 2014, 10(1): 13-28.
21.	Girlovanu M, Susman S, Soritau O, et al. Stem cells-biological update and cell therapy progress. Clujul Med, 2015, 88(3): 265-271.
22.	Kida Y, Morihara T, Matsuda K, et al. Bone marrow-derived cells from the footprint infiltrate into the repaired rotator cuff. J Shoulder Elbow Surg, 2013, 22(2): 197-205.
23.	Milano G, Saccomanno MF, Careri S, et al. Efficacy of marrow-stimulating technique in arthroscopic rotator cuff repair: a prospective randomized study. Arthroscopy, 2013, 29(5): 802-810.
24.	Snyder SJ, Burns J. Rotator cuff healing and the bone marrow “Crimson Duvet” from clinical observations to science. Techniques in Shoulder and Elbow Surgery, 2009, 10(4): 130-137.
25.	Tornero-Esteban P, Hoyas JA, Villafuertes E, et al. Efficacy of supraspinatus tendon repair using mesenchymal stem cells along with a collagen Ⅰ scaffold. J Orthop Surg Res, 2015, 10: 124.
26.	譚可可, 王秀秀, 張君, 等. 殼聚糖多孔支架復合 BMSCs 移植修復大鼠創傷性腦損傷的實驗研究. 中國修復重建外科雜志, 2018, 32(6): 745-752.
27.	Lau TT, Wang DA. Bioresponsive hydrogel scaffolding systems for 3D constructions in tissue engineering and regenerative medicine. Nanomedicine (Lond), 2013, 8(4): 655-668.
28.	Karageorgiou V, Kaplan D. Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials, 2005, 26(27): 5474-5491.
29.	Gulotta LV, Rodeo SA. Growth factors for rotator cuff repair. Clin Sports Med, 2009, 28(1): 13-23.
30.	Dai Y, Liu G, Ma L, et al. Cell-free macro-porous fibrin scaffolds for in situ inductive regeneration of full-thickness cartilage defects. J Mater Chem B, 2016, 4(25): 4410-4419.
31.	Sofu H, Kockara N, Oner A, et al. Results of hyaluronic acid-based cell-free scaffold application in combination with microfracture for the treatment of osteochondral lesions of the knee: 2-year comparative study. Arthroscopy, 2017, 33(1): 209-216.

1. Hurley ET, Maye AB, Mullett H. Arthroscopic rotator cuff repair: a systematic review of overlapping meta-analyses. JBJS Rev, 2019, 7(4): e1.
2. Li X, Cheng R, Sun Z, et al. Flexible bipolar nanofibrous membranes for improving gradient microstructure in tendon-to-bone healing. Acta Biomater, 2017, 61: 204-216.
3. Tsekes D, Konstantopoulos G, Khan WS, et al. Use of stem cells and growth factors in rotator cuff tendon repair. Eur J Orthop Surg Traumatol, 2019, 29(4): 747-757.
4. 潘娟, 劉國明, 寧良菊, 等. 脫細胞肌腱片促進兔肩袖損傷腱-骨愈合的實驗研究. 中國修復重建外科雜志, 2013, 27(9): 1070-1075.
5. He P, Ng KS, Toh SL, et al. In vitro ligament-bone interface regeneration using a trilineage coculture system on a hybrid silk scaffold. Biomacromolecules, 2012, 13(9): 2692-2703.
6. Sanzenbacher R, Dwenger A, Schuessler-Lenz M, et al. European regulation tackles tissue engineering. Nat Biotechnol, 2007, 25(10): 1089-1091.
7. Min HK, Oh SH, Lee JM, et al. Porous membrane with reverse gradients of PDGF-BB and BMP-2 for tendon-to-bone repair: in vitro evaluation on adipose-derived stem cell differentiation. Acta Biomater, 2014, 10(3): 1272-1279.
8. Narayanan G, Nair LS, Laurencin CT. Regenerative engineering of the rotator cuff of the shoulder. ACS Biomaterials Science & Engineering, 2018, 4(3): 751-786.
9. 高超, 李超明, 徐玉龍, 等. 靜電紡絲聚己內酯/Ⅰ型膠原納米纖維取向性補片用于肩袖修復. 中國修復重建外科雜志, 2019, 33(5): 628-633.
10. Zhu Q, Ma Z, Li H, et al. Enhancement of rotator cuff tendon-bone healing using combined aligned electrospun fibrous membranes and kartogenin. RSC Advances, 2019, 9(27): 15582-15592.
11. Bilsel K, Yildiz F, Kapicioglu M, et al. Efficacy of bone marrow-stimulating technique in rotator cuff repair. J Shoulder Elbow Surg, 2017, 26(8): 1360-1366.
12. Kon E, Filardo G, Perdisa F, et al. Acellular matrix-based cartilage regeneration techniques for osteochondral repair. Operative Techniques in Orthopaedics, 2014, 24(1): 14-18.
13. Degirmenci E, Ozturan KE, Sahin AA, et al. Effects of tranexamic acid on the recovery of osteochondral defects treated by microfracture and acellular matrix scaffold: an experimental study. J Orthop Surg Res, 2019, 14(1): 105.
14. 馬潞, 田猛. 可注射明膠原位水凝膠作為脫鈣骨基質粉末輸送載體可行性的初步研究. 中國修復重建外科雜志, 2017, 31(3): 300-305.
15. Yue K, Trujillo-de Santiago G, Alvarez MM, et al. Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels. Biomaterials, 2015, 73: 254-271.
16. Van Den Bulcke AI, Bogdanov B, De Rooze N, et al. Structural and rheological properties of methacrylamide modified gelatin hydrogels. Biomacromolecules, 2000, 1(1): 31-38.
17. Ide J, Kikukawa K, Hirose J, et al. Reconstruction of large rotator-cuff tears with acellular dermal matrix grafts in rats. J Shoulder Elbow Surg, 2009, 18(2): 288-295.
18. Font Tellado S, Balmayor ER, Van Griensven M. Strategies to engineer tendon/ligament-to-bone interface: Biomaterials, cells and growth factors. Adv Drug Deliv Rev, 2015, 94: 126-140.
19. 費文勇, 郭衛春. 成體干細胞技術促肩袖損傷修復實驗研究進展. 國際骨科學雜志, 2015, 36(1): 45-48.
20. Rothrauff BB, Tuan RS. Cellular therapy in bone-tendon interface regeneration. Organogenesis, 2014, 10(1): 13-28.
21. Girlovanu M, Susman S, Soritau O, et al. Stem cells-biological update and cell therapy progress. Clujul Med, 2015, 88(3): 265-271.
22. Kida Y, Morihara T, Matsuda K, et al. Bone marrow-derived cells from the footprint infiltrate into the repaired rotator cuff. J Shoulder Elbow Surg, 2013, 22(2): 197-205.
23. Milano G, Saccomanno MF, Careri S, et al. Efficacy of marrow-stimulating technique in arthroscopic rotator cuff repair: a prospective randomized study. Arthroscopy, 2013, 29(5): 802-810.
24. Snyder SJ, Burns J. Rotator cuff healing and the bone marrow “Crimson Duvet” from clinical observations to science. Techniques in Shoulder and Elbow Surgery, 2009, 10(4): 130-137.
25. Tornero-Esteban P, Hoyas JA, Villafuertes E, et al. Efficacy of supraspinatus tendon repair using mesenchymal stem cells along with a collagen Ⅰ scaffold. J Orthop Surg Res, 2015, 10: 124.
26. 譚可可, 王秀秀, 張君, 等. 殼聚糖多孔支架復合 BMSCs 移植修復大鼠創傷性腦損傷的實驗研究. 中國修復重建外科雜志, 2018, 32(6): 745-752.
27. Lau TT, Wang DA. Bioresponsive hydrogel scaffolding systems for 3D constructions in tissue engineering and regenerative medicine. Nanomedicine (Lond), 2013, 8(4): 655-668.
28. Karageorgiou V, Kaplan D. Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials, 2005, 26(27): 5474-5491.
29. Gulotta LV, Rodeo SA. Growth factors for rotator cuff repair. Clin Sports Med, 2009, 28(1): 13-23.
30. Dai Y, Liu G, Ma L, et al. Cell-free macro-porous fibrin scaffolds for in situ inductive regeneration of full-thickness cartilage defects. J Mater Chem B, 2016, 4(25): 4410-4419.
31. Sofu H, Kockara N, Oner A, et al. Results of hyaluronic acid-based cell-free scaffold application in combination with microfracture for the treatment of osteochondral lesions of the knee: 2-year comparative study. Arthroscopy, 2017, 33(1): 209-216.

Chinese Journal of Reparative and Reconstructive Surgery

Effect of microfracture combined with biomimetic hydrogel scaffold on rotator cuff tendon-to-bone healing in rabbits

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