Abstract
Reconstruction of bone defects is still a significant challenge. The aim of this study was to evaluate the effect of application of photobiomodulation (PBM) to enhance in vivo bone regeneration and osteogenic differentiation potential of adipose-derived stem cells (ADSCs) encapsulated in methacrylated gelatin (GEL-MA) hydrogels. Thirty-six Sprague-Dawley rats were randomly separated into 3 experimental groups (n = 12 each). The groups were control/blank defect (I), GEL-MA hydrogel (II), and ADSC-loaded GEL-MA (GEL-MA+ADSC) hydrogel (III). Biparietal critical sized bone defects (6 mm in size) are created in each animal. Half of the animals from each group (n = 6 each) were randomly selected for PBM application using polychromatic light in the near infrared region, 600–1200 nm. PBM was administered from 10 cm distance cranially in 48 h interval. The calvaria were harvested at the 20th week, and macroscopic, microtomographic, and histologic evaluation were performed for further analysis. Microtomographic evaluation demonstrated the highest result for mineralized matrix formation (MMF) in group III. PBM receiving samples of group III showed mean MMF of 79.93±3.41%, whereas the non-PBM receiving samples revealed mean MMF of 60.62±6.34 % (p=0.002). In terms of histologic evaluation of bone defect repair, the higher scores were obtained in the groups II and III when compared to the control group (2.0 for both PBM receiving and non-receiving specimens; p<0.001). ADSC-loaded microwave-induced GEL-MA hydrogels and periodic application of photobiomodulation with polychromatic light appear to have beneficial effect on bone regeneration and can stimulate ADSCs for osteogenic differentiation.
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References
Fearon JA, Griner D, Ditthakasem K, Herbert M (2017) Autogenous bone reconstruction of large secondary skull defects. Plast Reconstr Surg 139:427–438
Perry CR (1999) Bone repair techniques, bone graft, and bone graft substitutes. Clin Orthop Relat Res:71–86
McCarthy JG, Stelnicki EJ, Mehrara BJ, Longaker MT (2001) Distraction osteogenesis of the craniofacial skeleton. Plast Reconstr Surg 107:1812–1827
Roseti L, Parisi V, Petretta M, Cavallo C, Desando G, Bartolotti I, Grigolo B (2017) Scaffolds for bone tissue engineering: State of the art and new perspectives. Mater Sci Eng C Mater Biol Appl 78:1246–1262
Zhang YS, Khademhosseini A (2017) Advances in engineering hydrogels. Science 356
Kim BS, Cho CS (2018) Injectable hydrogels for regenerative medicine. Tissue Eng Regen Med 15:511–512
Fang XX, Xie J, Zhong LX, Li JR, Rong DM, Li XS, Ouyang J (2016) Biomimetic gelatin methacrylamide hydrogel scaffolds for bone tissue engineering. J Mater Chem B 4:1070–1080
Van den Bulcke AI, Bogdanov B, De Rooze N, Schacht EH, Cornelissen M, Berghmans H (2000) Structural and rheological properties of methacrylamide modified gelatin hydrogels. Biomacromolecules 1:31–38
Irmak G, Demirtas TT, Gumusderelioglu M (2019) Highly methacrylated gelatin bioink for bone tissue engineering. Acs Biomater Sci Eng 5:831–845
Mester E, Spiry T, Szende B, Tota JG (1971) Effect of laser rays on wound healing. Am J Surg 122:532–535
Dodd EM, Winter MA, Hordinsky MK, Sadick NS, Farah RS (2018) Photobiomodulation therapy for androgenetic alopecia: a clinician’s guide to home-use devices cleared by the Federal Drug Administration. J Cosmet Laser Ther 20:159–167
Hennessy M, Hamblin MR (2017) Photobiomodulation and the brain: a new paradigm. J Opt 19:013003
Kuffler DP (2016) Photobiomodulation in promoting wound healing: a review. Regen Med 11:107–122
Karu T (1989) Laser biostimulation: a photobiological phenomenon. J Photochem Photobiol B 3:638–640
Irmak G, Demirtaş TT, Gümüşderelioğlu M (2019) Sustained release of growth factor from photoactivated platelet rich plasma (PRP). Eur J Pharm Biopharm 2020 Mar 148:67–76
Gupta A, Avci P, Sadasivam M, Chandran R, Parizotto N, Vecchio D, de Melo WC, Dai T, Chiang LY, Hamblin MR (2013) Shining light on nanotechnology to help repair and regeneration. Biotechnol Adv 31:607–631
Ulker N, Cakmak AS, Kiremitci AS, Gumusderelioglu M (2016) Polychromatic light-induced osteogenic activity in 2D and 3D cultures. Lasers Med Sci 31:1665–1674
Soleimani M, Abbasnia E, Fathi M, Sahraei H, Fathi Y, Kaka G (2012) The effects of low-level laser irradiation on differentiation and proliferation of human bone marrow mesenchymal stem cells into neurons and osteoblasts-an in vitro study. Lasers Med Sci 27:423–430
Cakmak AS, Cakmak S, Vatansever HS, Gumusderelioglu M (2018) Photostimulation of osteogenic differentiation on silk scaffolds by plasma arc light source. Lasers Med Sci 33:785–794. https://doi.org/10.1007/s10103-017-2414-4
El Nawam H, El Backly R, Zaky A, Abdallah A (2019) Low-level laser therapy affects dentinogenesis and angiogenesis of in vitro 3D cultures of dentin-pulp complex. Lasers Med Sci 34:1689–1698
Lin F, Josephs SF, Alexandrescu DT, Ramos F, Bogin V, Gammill V, Dasanu CA, De Necochea-Campion R, Patel AN, Carrier E, Koos DR (2010) Lasers, stem cells, and COPD. J Transl Med 8:16
Oliveira FA, Matos AA, Santesso MR, Tokuhara CK, Leite AL, Bagnato VS, Machado MA, Peres-Buzalaf C, Oliveira RC (2016) Low intensity lasers differently induce primary human osteoblast proliferation and differentiation. J Photochem Photobiol B 163:14–21
Calis M, Demirtas TT, Sert G, Irmak G, Gumusderelioglu M, Turkkani A, Cakar AN, Ozgur F (2019) Photobiomodulation with polychromatic light increases zone 4 survival of transverse rectus abdominis musculocutaneous flap. Lasers Surg Med 51:538–549
Akdere OE, Shikhaliyeva I, Gumusderelioglu M (2019) Boron mediated 2D and 3D cultures of adipose derived mesenchymal stem cells. Cytotechnology 71:611–622
Bolgen N, Vargel I, Korkusuz P, Guzel E, Plieva F, Galaev I, Matiasson B, Piskin E (2009) Tissue responses to novel tissue engineering biodegradable cryogel scaffolds: an animal model. J Biomed Mater Res A 91:60–68
Preethi Soundarya S, Haritha Menon A, Viji Chandran S, Selvamurugan N (2018) Bone tissue engineering: scaffold preparation using chitosan and other biomaterials with different design and fabrication techniques. Int J Biol Macromol 119:1228–1239
Mishra R, Bishop T, Valerio IL, Fisher JP, Dean D (2016) The potential impact of bone tissue engineering in the clinic. Regen Med 11:571–587
Roddy E, DeBaun MR, Daoud-Gray A, Yang YP, Gardner MJ (2018) Treatment of critical-sized bone defects: clinical and tissue engineering perspectives. Eur J Orthop Surg Traumatol 28:351–362
Panetta NJ, Gupta DM, Longaker MT (2009) Bone tissue engineering scaffolds of today and tomorrow. J Craniofac Surg 20:1531–1532
Calis M, Demirtas TT, Vatansever A, Irmak G, Sakarya AH, Atilla P, Ozgur F, Gumusderelioglu M (2017) A biomimetic alternative to synthetic hydroxyapatite: “boron-containing bone-like hydroxyapatite” precipitated from simulated body fluid. Ann Plast Surg 79:304–311
Bakhshandeh B, Zarrintaj P, Oftadeh MO, Keramati F, Fouladiha H, Sohrabi-Jahromi S, Ziraksaz Z (2017) Tissue engineering; strategies, tissues, and biomaterials. Biotechnol Genet Eng Rev 33:144–172
Paschos NK, Brown WE, Eswaramoorthy R, Hu JC, Athanasiou KA (2015) Advances in tissue engineering through stem cell-based co-culture. J Tissue Eng Regen Med 9:488–503
Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13:4279–4295
Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7:211–228
Calis M, Demirtas TT, Atilla P, Tatar I, Ersoy O, Irmak G, Celik HH, Cakar AN, Gumusderelioglu M, Ozgur F (2014) Estrogen as a novel agent for induction of adipose-derived mesenchymal stem cells for osteogenic differentiation: in vivo bone tissue-engineering study. Plast Reconstr Surg 133:499e–510e
Mester E, Nagylucskay S, Tisza S, Mester A (1978) Stimulation of wound healing by means of laser rays. Part III--investigation of the effect on immune competent cells. Acta Chir Acad Sci Hung 19:163–170
Mester E, Spiry T, Szende B (1973) Effect of laser rays on wound healing. Bull Soc Int Chir 32:169–173
Aimbire F, Albertini R, Pacheco MT, Castro-Faria-Neto HC, Leonardo PS, Iversen VV, Lopes-Martins RA, Bjordal JM (2006) Low-level laser therapy induces dose-dependent reduction of TNFalpha levels in acute inflammation. Photomed Laser Surg 24:33–37
Lubart R, Lavi R, Friedmann H, Rochkind S (2006) Photochemistry and photobiology of light absorption by living cells. Photomed Laser Surg 24:179–185
Karu T (1999) Primary and secondary mechanisms of action of visible to near-IR radiation on cells. J Photochem Photobiol B 49:1–17
Medrado AP, Soares AP, Santos ET, Reis SR, Andrade ZA (2008) Influence of laser photobiomodulation upon connective tissue remodeling during wound healing. J Photochem Photobiol B 92:144–152
Brightman LA, Brauer JA, Anolik R, Weiss ET, Karen J, Chapas A, Hale E, Bernstein L, Geronemus RG (2011) Reduction of thickened flap using fractional carbon dioxide laser. Lasers Surg Med 43:873–874
Abinaya B, Prasith TP, Ashwin B, Viji Chandran S, Selvamurugan N (2019) Chitosan in surface modification for bone tissue engineering applications. Biotechnol J:e1900171
Hollinger JO, Schmitt JM, Buck DC, Shannon R, Joh SP, Zegzula HD, Wozney J (1998) Recombinant human bone morphogenetic protein-2 and collagen for bone regeneration. J Biomed Mater Res 43:356–364
Nichol JW, Koshy ST, Bae H, Hwang CM, Yamanlar S, Khademhosseini A (2010) Cell-laden microengineered gelatin methacrylate hydrogels. Biomaterials 31:5536–5544
Klotz BJ, Gawlitta D, Rosenberg A, Malda J, Melchels FPW (2016) Gelatin-methacryloyl hydrogels: Towards biofabrication-based tissue repair. Trends Biotechnol 34:394–407
Djagny VB, Wang Z, Xu S (2001) Gelatin: a valuable protein for food and pharmaceutical industries: review. Crit Rev Food Sci Nutr 41:481–492
Lai JY, Li YT (2010) Functional assessment of cross-linked porous gelatin hydrogels for bioengineered cell sheet carriers. Biomacromolecules 11:1387–1397
Si Z, Wang X, Sun C, Kang Y, Xu J, Wang X, Hui Y (2019) Adipose-derived stem cells: sources, potency, and implications for regenerative therapies. Biomed Pharmacother 114:108765
Fraser J, Wulur I, Alfonso Z, Zhu M, Wheeler E (2007) Differences in stem and progenitor cell yield in different subcutaneous adipose tissue depots. Cytotherapy 9:459–467
Barbatelli G, Murano I, Madsen L, Hao Q, Jimenez M, Kristiansen K, Giacobino JP, De Matteis R, Cinti S (2010) The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation. Am J Physiol Endocrinol Metab 298:E1244–E1253
Baer PC, Koch B, Hickmann E, Schubert R, Cinatl J Jr, Hauser IA, Geiger H (2019) Isolation, characterization, differentiation and immunomodulatory capacity of mesenchymal stromal/stem cells from human perirenal adipose tissue. Cells 2019 Oct 29 8(11):0
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This work was supported from the Hacettepe University Scientific Research Foundation (Grant No: THD-2017-14465).
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Mert Calis designed the animal study, conducted the experiments, and wrote the paper. Murat Kara and Galip Gencay Üstün contributed the animal experiments, postoperative care, and application of the PBM. Gülseren Irmak and Tuğrul Tolga Demirtaş prepared the stem cells and the biomaterials for the study. Tuğrul Tolga Demirtaş and Mert Calis performed the microCT analyses. Ayşe Nur Çakar and Ayten Türkkanı performed the histological analyses. Menemşe Gümüşderelioğlu and Figen Özgür designed and supervised the study and edited the final manuscript.
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The study was conducted, and all animal experiments were performed following approval of the Institutional Review Board of Hacettepe University on Experimental Studies (Approval no.: 2017/29-04).
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Calis, M., Irmak, G., Demirtaş, T.T. et al. Photobiomodulation combined with adipose-derived stem cells encapsulated in methacrylated gelatin hydrogels enhances in vivo bone regeneration. Lasers Med Sci 37, 595–606 (2022). https://doi.org/10.1007/s10103-021-03308-y
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DOI: https://doi.org/10.1007/s10103-021-03308-y