Visible light mediated PVA-tyramine hydrogels for covalent incorporation and tailorable release of functional growth factors

Atienza‐Roca, Pau; Kieser, David; Cui, Xiaolin; Bathish, Boushra; Ramaswamy, Yogambha; Hooper, Gary J.; Clarkson, Andrew N.; Rnjak‐Kovacina, Jelena; Martens, Penny J.; Wise, Lyn M.; Woodfield, Tim B. F.; Lim, Khoon S.

doi:10.1039/d0bm00603c

Cited by 30 publications

(46 citation statements)

References 75 publications

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“…The LC–MS/MS examinations were performed based on the protocol previously reported. [ 35 ] Briefly, all gels used for LC–MS/MS analyses were prepared as mentioned in the auto‐fluoresce experiment. The fabricated hydrogel constructs were hydrolyzed using 4 m methanesulfonic acid containing 1 wt% phenol under the nitrogen environment for 18 h. Solid phase extraction (SPE) using Strata C18‐E (55 µm, 70 Å) cartridges was performed to the hydrolysate process to remove the acid and was eluted with 80% (v/v) methyl alcohol.…”

Section: Methodsmentioning

confidence: 99%

“…[13,33,34] Second, the high molar extinction coefficient allows efficient curing reaction at a relatively low initiator concentrations. [35] Third, the high penetration depth is effectual to overall the curing of the large constructs homogenously. [33,36] Ru-based photoinitiators have already been applied to the cross-linking of fibrin-, collagen-, as well as silkbased natural biomaterials.…”

Section: Introductionmentioning

confidence: 99%

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Light‐Activated Decellularized Extracellular Matrix‐Based Bioinks for Volumetric Tissue Analogs at the Centimeter Scale

Kim

Kang

Cui

et al. 2021

Adv Funct Materials

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Tissue engineering requires not only tissue‐specific functionality but also a realistic scale. Decellularized extracellular matrix (dECM) is presently applied to the extrusion‐based 3D printing technology. It has demonstrated excellent efficiency as bioscaffolds that allow engineering of living constructs with elaborate microarchitectures as well as the tissue‐specific biochemical milieu of target tissues and organs. However, dECM bioinks have poor printability and physical properties, resulting in limited shape fidelity and scalability. In this study, new light‐activated dECM bioinks with ruthenium/sodium persulfate (dERS) are introduced. The materials can be polymerized via a dityrosine‐based cross‐linking system with rapid reaction kinetics and improved mechanical properties. Complicated constructs with high aspect ratios can be fabricated similar to the geometry of the desired constructs with increased shape fidelity and excellent printing versatility using dERS. Furthermore, living tissue constructs can be safely fabricated with excellent tissue regenerative capacity identical to that of pure dECM. dERS may serve as a platform for a wider biofabrication window through building complex and centimeter‐scale living constructs as well as supporting tissue‐specific performances to encapsulated cells. This capability of dERS opens new avenues for upscaling the production of hydrogel‐based constructs without additional materials and processes, applicable in tissue engineering and regenerative medicine.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Light‐Activated Decellularized Extracellular Matrix‐Based Bioinks for Volumetric Tissue Analogs at the Centimeter Scale

Kim

Kang

Cui

et al. 2021

Adv Funct Materials

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“…27 The long time frame of release (tailored to 21 days) and the secure bonding of GFs ensured predictable and linear release of the GFs. 6,27 In this rat supraspinatus repair model, the GF combination led to significantly improved histological appearances at 6 and 12 weeks. As hypothesized, anabolic effects on the tendon and enthesis resulted in superior collagen fiber density and the formation of an early fibrocartilage enthesis in the experimental group at 6 weeks.…”

Section: Discussionmentioning

confidence: 87%

Novel Growth Factor Combination for Improving Rotator Cuff Repair: A Rat In Vivo Study

et al. 2022

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Background: The lack of healing at the repaired tendon-bone interface is an important cause of failure after rotator cuff repair. While augmentation with growth factors (GFs) has demonstrated promise, the ideal combination must target all 3 tissue types at the tendon-bone interface. Hypothesis: The GF combination of transforming growth factor beta 1, Insulin-like growth factor 1, and parathyroid hormone will promote tenocyte proliferation and differentiation and improve the biomechanical and histological quality of the repaired tendon-bone interface. Study Design: Controlled laboratory study. Methods: In vitro, human tenocytes were cultured in the presence of the GF combination for 72 hours, and cell growth assays and the expression of genes specific to tendon, cartilage, and bone were analyzed. In vivo, adult rats (N = 46) underwent detachment and repair of the left supraspinatus tendon. A PVA-tyramine gel was used to deliver the GF combination to the tendon-bone interface. Histological, biomechanical, and RNA microarray analysis was performed at 6 and 12 weeks after surgery. Immunohistochemistry for type II and X collagen was performed at 12 weeks. Results: When treated with the GF combination in vitro, human tenocytes proliferated 1.5 times more than control ( P = .04). The expression of scleraxis increased 65-fold ( P = .013). The expression of Sox-9 ( P = .011), type I collagen ( P = .021), fibromodulin ( P = .0075), and biglycan ( P = .010) was also significantly increased, while the expression of PPARγ was decreased ( P = .007). At 6 and 12 weeks postoperatively, the quality of healing on histology was significantly higher in the GF group, with the formation of a more mature tendon-bone interface, as confirmed by immunohistochemistry for type II and X collagen. The GF group achieved a load at failure and Young modulus >1.5 times higher at both time points. Microarrays at 6 weeks demonstrated upregulation of genes involved in leukocyte aggregation ( S100A8, S100A9) and tissue mineralization ( Bglap, serglycin, Fam20c). Conclusion: The GF combination promoted protendon and cartilage responses in human tenocytes in vitro; it also improved the histological appearance and mechanical properties of the repair in vivo. Microarrays of the tendon-bone interface identified inflammatory and mineralization pathways affected by the GF combination, providing novel therapeutic targets for further research. Clinical Relevance: The use of this GF combination is translatable to patients and may improve healing after rotator cuff repair.

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“…Synthetic bioinks have thus been used since the beginning of the biofabrication era. Key examples includes the use of Polyethylene glycols (PEGs) [ 63 , 64 , 65 , 66 ], Poly(vinyl alcohol) (PVA) [ 46 , 67 , 68 , 69 ], N-isopropylacrylamide (NIPAAm) [ 70 , 71 ], and polyacrylamide (PAAm) [ 72 , 73 , 74 ]. In this section, recent developments and clinical advantages of these materials are highlighted.…”

Section: Designing Musculoskeletal Bioinksmentioning

confidence: 99%

“…These scaffolds may be applied as cell-free products, with a shorter path to the clinic. Using clever chemistry modification strategies, PVA hydrogels can furthermore be designed to be hydrolytically degradable to help control the delivery of bioactive factors to surrounding cells [ 68 ]. Musculoskeletal factors such as VEGF, bFGF and BMP can be delivered with tailorable long-term release profiles, reaching over three months of sustained release.…”

Section: Designing Musculoskeletal Bioinksmentioning

confidence: 99%

Biofabrication Strategies for Musculoskeletal Disorders: Evolution towards Clinical Applications

et al. 2021

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Biofabrication has emerged as an attractive strategy to personalise medical care and provide new treatments for common organ damage or diseases. While it has made impactful headway in e.g., skin grafting, drug testing and cancer research purposes, its application to treat musculoskeletal tissue disorders in a clinical setting remains scarce. Albeit with several in vitro breakthroughs over the past decade, standard musculoskeletal treatments are still limited to palliative care or surgical interventions with limited long-term effects and biological functionality. To better understand this lack of translation, it is important to study connections between basic science challenges and developments with translational hurdles and evolving frameworks for this fully disruptive technology that is biofabrication. This review paper thus looks closely at the processing stage of biofabrication, specifically at the bioinks suitable for musculoskeletal tissue fabrication and their trends of usage. This includes underlying composite bioink strategies to address the shortfalls of sole biomaterials. We also review recent advances made to overcome long-standing challenges in the field of biofabrication, namely bioprinting of low-viscosity bioinks, controlled delivery of growth factors, and the fabrication of spatially graded biological and structural scaffolds to help biofabricate more clinically relevant constructs. We further explore the clinical application of biofabricated musculoskeletal structures, regulatory pathways, and challenges for clinical translation, while identifying the opportunities that currently lie closest to clinical translation. In this article, we consider the next era of biofabrication and the overarching challenges that need to be addressed to reach clinical relevance.

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Visible light mediated PVA-tyramine hydrogels for covalent incorporation and tailorable release of functional growth factors

Abstract: The translation of growth factors (GFs) into clinical applications is limited by their low stability in physiological environments. Controlled GF delivery through biomaterial vehicles provides protection from proteases, targeted delivery,...

Cited by 30 publications

References 75 publications

Light‐Activated Decellularized Extracellular Matrix‐Based Bioinks for Volumetric Tissue Analogs at the Centimeter Scale

Light‐Activated Decellularized Extracellular Matrix‐Based Bioinks for Volumetric Tissue Analogs at the Centimeter Scale

Novel Growth Factor Combination for Improving Rotator Cuff Repair: A Rat In Vivo Study

Biofabrication Strategies for Musculoskeletal Disorders: Evolution towards Clinical Applications

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