Vascularization in tissue engineering: The architecture cues of pores in scaffolds

Xia, Peng; Luo, Yongxiang

doi:10.1002/jbm.b.34979

Cited by 35 publications

(16 citation statements)

References 96 publications

(101 reference statements)

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“…[ 89,94–99 ] The combination of such macroporous materials and cells furthermore enabled to locally provide a highly porous, cellularized scaffold material. [ 100,101 ] In agreement with previous reports [ 102,103 ] discussing the influence of porous scaffold materials, the macroporosity introduced by µ‐gels greatly enhanced vascularization. Different from previous reports, [ 104 ] the presented method leveraged mechanical sizing and allowed for a microfluidic‐ and emulsification‐free biofabrication process.…”

Section: Resultssupporting

confidence: 90%

Enzymatically Crosslinked Collagen as a Versatile Matrix for In Vitro and In Vivo Co‐Engineering of Blood and Lymphatic Vasculature

et al. 2023

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are missing extensive pericyte coverage. In addition, lymphatics exhibit an irregularly shaped or collapsed lumen lacking red blood cells (RBCs). [1][2][3] Lymphatic vascular structures are generally classified as either capillaries (diameter 10-60 µm) or collecting lymphatic vessels (diameter 50-200 µm). [4] Similarly, blood vessels can be categorized into either capillaries (4-10 µm) or larger structures such as arterioles and venules (10-100 µm). [5] Despite their structural differences, the blood and lymphatic vasculature are closely interconnected on a functional level to ensure nutritional supply of cells and tissue homeostasis. [6][7][8] The absence of a functional vascular network in vitro is one of the main drawbacks of many bioengineered tissues and a frequent cause of necrosis in vivo. [9] Whereas most previous studies focused on the blood vasculature, recent discoveries have brought increased attention to the role of lymphatics and their role in tissue regeneration. [7,8] Yet only a few studies have so far attempted to co-engineer blood and lymphatic microcapillaries. Marino et al. described a simple co-culturing system of blood endothelial cells (BECs) and lymphatic endothelial cells (LECs) based on native fibrin and collagen hydrogels. [10] The resulting microcapillaries remained in their early developmental stages, with phenotypes exhibiting mostly short capillary fragments Adequate vascularization is required for the successful translation of many in vitro engineered tissues. This study presents a novel collagen derivative that harbors multiple recognition peptides for orthogonal enzymatic crosslinking based on sortase A (SrtA) and Factor XIII (FXIII). SrtA-mediated crosslinking enables the rapid co-engineering of human blood and lymphatic microcapillaries and mesoscale capillaries in bulk hydrogels. Whereas tuning of gel stiffness determines the extent of neovascularization, the relative number of blood and lymphatic capillaries recapitulates the ratio of blood and lymphatic endothelial cells originally seeded into the hydrogel. Bioengineered capillaries readily form luminal structures and exhibit typical maturation markers both in vitro and in vivo. The secondary crosslinking enzyme Factor XIII is used for in situ tethering of the VEGF mimetic QK peptide to collagen. This approach supports the formation of blood and lymphatic capillaries in the absence of exogenous VEGF. Orthogonal enzymatic crosslinking is further used to bioengineer hydrogels with spatially defined polymer compositions with pro-and anti-angiogenic properties. Finally, macroporous scaffolds based on secondary crosslinking of microgels enable vascularization independent from supporting fibroblasts. Overall, this work demonstrates for the first time the co-engineering of mature micro-and meso-sized blood and lymphatic capillaries using a highly versatile collagen derivative.

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Section: Resultssupporting

confidence: 90%

Enzymatically Crosslinked Collagen as a Versatile Matrix for In Vitro and In Vivo Co‐Engineering of Blood and Lymphatic Vasculature

et al. 2023

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“…Modulation of material pore size has been shown to be an important parameter in modulating fouling characteristics of materials [39] and their severity of the foreign body response [40] along with ensuring sufficient mass transport and vascularization potential. [41,42]…”

Section: Porositymentioning

confidence: 99%

Tailored Biocompatible Polyurethane‐Poly(ethylene glycol) Hydrogels as a Versatile Nonfouling Biomaterial

Speidel

Wood

Roberts

et al. 2022

Adv Healthcare Materials

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Polyurethane-based hydrogels are relatively inexpensive and mechanically robust biomaterials with ideal properties for various applications, including drug delivery, prosthetics, implant coatings, soft robotics, and tissue engineering. In this report, a simple method is presented for synthesizing and casting biocompatible polyurethane-poly(ethylene glycol) (PU-PEG) hydrogels with tunable mechanical properties, nonfouling characteristics, and sustained tolerability as an implantable material or coating. The hydrogels are synthesized via a simple one-pot method using commercially available precursors and low toxicity solvents and reagents, yielding a consistent and biocompatible gel platform primed for long-term biomaterial applications. The mechanical and physical properties of the gels are easily controlled by varying the curing concentration, producing networks with complex shear moduli of 0.82-190 kPa, similar to a range of human soft tissues. When evaluated against a mechanically matched poly(dimethylsiloxane) (PDMS) formulation, the PU-PEG hydrogels demonstrated favorable nonfouling characteristics, including comparable adsorption of plasma proteins (albumin and fibrinogen) and significantly reduced cellular adhesion. Moreover, preliminary murine implant studies reveal a mild foreign body response after 41 days. Due to the tunable mechanical properties, excellent biocompatibility, and sustained in vivo tolerability of these hydrogels, it is proposed that this method offers a simplified platform for fabricating soft PU-based biomaterials for a variety of applications.

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“…The pore structure, e.g., size, porosity, and interconnectivity, of a porous drug-loaded carrier plays an important role not only in the drug release profile but also in the new tissue in-growth . As reported in our previous study, the impregnation of 420 mg of PMCM-41 in the solution of 200 mg of CDM in 3 mL of DI water at ambient temperature for 24 h yielded the nanoparticles loaded with approximately 30% by weight of CDM (coded as PMC), determined by TGA-DTA.…”

Section: Resultsmentioning

confidence: 61%

Dual-Functional Drug Delivery System for Bisphosphonate-Related Osteonecrosis Prevention and Its Bioinspired Releasing Model and In Vitro Assessment

et al. 2023

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Clindamycin (CDM)/geranylgeraniol (GGOH)-loaded plasma-treated mesoporous silica nanoparticles/carboxymethyl chitosan composite hydrogels (CHG60 and CHG120) were developed for the prevention of medication-related osteonecrosis of the jaw associated with bisphosphonates (MRONJ-B). The pore structure and performances of CHGs, e.g., drug release profiles and kinetics, antibacterial activity, zoledronic acid (ZA)-induced cytotoxicity reversal activity, and acute cytotoxicity, were evaluated. The bioinspired platform mimicking in vivo fibrin matrices was also proposed for the in vitro/in vivo correlation. CHG120 was further encapsulated in the human-derived fibrin, generating FCHG120. The SEM and μCT images revealed the interconnected porous structures of CHG120 in both pure and fibrin-surrounding hydrogels with %porosity of 75 and 36%, respectively, indicating the presence of fibrin inside the hydrogel pores, besides its peripheral region, which was evidenced by confocal microscopy. The co-presence of GGOH moderately decelerated the overall releases of CDM from CHGs in the studied releasing fluids, i.e., phosphate buffer saline-based fluid (PBB) and simulated interstitial fluid (SIF). The whole-lifetime release patterns of CDM, fitted by the Ritger–Peppas equation, appeared nondifferentiable, divided into two releasing stages, i.e., rapid and steady releasing stages, whereas the biphasic drug release patterns of GGOH were observed with Phase I and II releases fitted by the Higuchi and Ritger–Peppas equations, respectively. Notably, the burst releases of both drugs were subsided with lengthier durations (up to 10–12 days) in SIF, compared with those in PBB, enabling CHGs to elicit satisfactory antibacterial and ZA cytotoxicity reversal activities for MRONJ-B prevention. The fibrin network in FCHG120 further reduced and sustained the drug releases for at least 14 days, lengthening bactericidal and ZA cytotoxicity reversal activities of FCHG and decreasing in vitro and in ovo acute drug toxicity. This highlighted the significance of fibrin matrices as appropriate in vivo-like platforms to evaluate the performance of an implant.

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Vascularization in tissue engineering: The architecture cues of pores in scaffolds

Cited by 35 publications

References 96 publications

Enzymatically Crosslinked Collagen as a Versatile Matrix for In Vitro and In Vivo Co‐Engineering of Blood and Lymphatic Vasculature

Enzymatically Crosslinked Collagen as a Versatile Matrix for In Vitro and In Vivo Co‐Engineering of Blood and Lymphatic Vasculature

Tailored Biocompatible Polyurethane‐Poly(ethylene glycol) Hydrogels as a Versatile Nonfouling Biomaterial

Dual-Functional Drug Delivery System for Bisphosphonate-Related Osteonecrosis Prevention and Its Bioinspired Releasing Model and In Vitro Assessment

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