Biocompatibility evaluation of bioprinted decellularized collagen sheet implanted in vivo cornea using swept‐source optical coherence tomography

Abstract

Corneal transplantation by full-thickness penetrating keratoplasty with human donor tissue is a widely accepted treatment for damaged or diseased corneas.Although corneal transplantation has a high success rate, a shortage of highquality donor tissue is a considerable limitation. Therefore, bioengineered corneas could be an effective solution for this limitation, and a decellularized extracellular matrix comprises a promising scaffold for their fabrication. In this study, three-dimensional bioprinted decellularized collagen sheets were implanted into the stromal layer of the cornea of five rabbits. We performed in vivo noninvasive monitoring of the rabbit corneas using swept-source optical coherence tomography (OCT) after implanting the collagen sheets. Anterior segment OCT images and averaged amplitude-scans were acquired biweekly to monitor corneal thickness after implantation for 1 month. The averaged cornea thickness in the control images was 430.3 ± 5.9 μm, while the averaged thickness after corneal implantation was 598.5 ± 11.8 μm and 564.5 ± 12.5 μm at 2 and 4 weeks, respectively. The corneal thickness reduction of 34 μm confirmed the biocompatibility through the image analysis of the depth-intensity profile base. Moreover, hematoxylin and eosin staining supported the biocompatibility evaluation of the bioprinted decellularized collagen sheet implantation. Hence, the developed bioprinted decellularized collagen sheets could become an alternative solution to human corneal donor tissue, and the proposed image analysis procedure could be beneficial to confirm the success of the surgery. Jaeseok Park, Kyoung-Pil Lee and Hyeonji Kim contributed equally to this work.

Designing Scaffolds for Corneal Regeneration

“…The problem can be partially overcome by printing cylindrical rather than hemispherical corneal constructs although this introduces a new problem since the construct will probably differ in shape to the tissue it is replacing. [245] Another potential limitation with bioprinting is the difficulty to replicate the collagen fibril organization found in the stroma. To overcome this problem, Kim et al utilized the shear flow properties of the bioink during printing to direct fibrils in the desired orientations.…”

“…This is a limitation of the printing process itself since to generate a curvature by printing flat layers, each printed layer needs to be slightly offset from the previous layer. The problem can be partially overcome by printing cylindrical rather than hemispherical corneal constructs although this introduces a new problem since the construct will probably differ in shape to the tissue it is replacing 245. Another potential limitation with bioprinting is the difficulty to replicate the collagen fibril organization found in the stroma.…”

From Shape to Function: The Next Step in Bioprinting

“…Printable, cell compatible bioinks have been obtained by decellularizing and solubilizing ECM from adipose tissue, cartilage and cardiac muscle, and each of these bioinks was proven superior to collagen gels in view of their potential to induce differentiation of adipose derived stromal cells, bone‐marrow derived stromal cells, and cardiomyocites, respectively . In fact, a variety of tissue‐specific dECM inks have now been produced from tissues, including liver, brain, skin, skeletal muscle, and cornea …”

“…[ 85 , 232 ] In fact, a variety of tissue-specific dECM inks have now been produced from tissues, including liver, [ 92 ] brain, [ 233 ] skin, [ 234 ] skeletal muscle, [ 91 ] and cornea. [ 235 ]…”

Intra-Operative Optical Coherence Imaging of In-Vivo Chronic Otitis Media Followed by Post-Operative Audiogram Assessments

“…During the last decade, optical coherence tomography (OCT) has been well-utilized intra-operatively for high-resolution subsurface visualization to improve the proportion of successful operation in otolaryngology and ophthalmology [17][18][19][20]. Besides its intra-operative applications, OCT techniques over the last two decades have been promisingly recognized for ophthalmology [21][22][23], dentistry [24][25][26][27], dermatology [28][29][30][31], and otorhinolaryngology [32,33]. The high-resolution of OCT (1-15 μm ) has vital merits in otology over other medical imaging methods, such as its ability to image a thin sub-surface, low contrast TM, and complicated middle ear structures compared to that of the computed tomography (CT) (50 μm), micro-magnetic resonance imaging (μMRI) (10-100 μm), and positron emission tomography (PET) (1-2 mm) [34,35].…”