3D Bioprinted Patient‐Specific Extracellular Matrix Scaffolds for Soft Tissue Defects

Abstract

Soft tissue injuries such as volumetric muscle loss (VML) are often too large to heal normally on their own, resulting in scar formation and functional deficits. Decellularized extracellular matrix (dECM) scaffolds placed into these wounds have shown the ability to modulate the immune response and drive constructive healing. This provides a potential solution for functional tissue regeneration, however, these acellular dECM scaffolds are challenging to fabricate into complex geometries. 3D bioprinting is uniquely positioned to address this, being able to create patient-specific scaffolds based on clinical 3D imaging data. Here, a process to use freeform reversible embedding of suspended hydrogels (FRESH) 3D bioprinting and computed tomography (CT) imaging to build large volume, patient-specific dECM patches (≈12 × 8 × 2 cm) for implantation into canine VML wound models is developed. Quantitative analysis shows that these dECM patches are dimensionally accurate and conformally adapt to the surface of complex wounds. Finally, this approach is extended to a human VML injury to demonstrate the fabrication of clinically relevant dECM scaffolds with precise control over fiber alignment and micro-architecture. Together these advancements represent a step towards an improved, clinically translatable, patient-specific treatment for soft tissue defects from trauma, tumor resection, and other surgical procedures.

Preparation and Use of Decellularized Extracellular Matrix for Tissue Engineering

“…The patch was able to make better contact with fewer air voids between the patch and the tissue than an onlay EMC sheet (99.9% touching the wound compared to 90.3%, respectively). They also demonstrated that it might be possible to create similar scaffolds for volumetric muscle loss injuries in human patients [ 344 ]. Chen L et al (2022) developed a hydrogel from dermis dECM that they used as a 3D-printed, glutaraldehyde-cross-linked underlay for split-thickness skin grafts.…”

Advancements in 3D‐printed artificial tendon

“…variety of tissues like muscle, fat, skin, and blood vessels, which have diverse cellular compositions and arrangements. 22…”

“…Bone tissue is a mineralized connective tissue containing cells, collagen fibers, and hydroxyapatite crystals, providing strength and support 21 . Soft tissues, on the other hand, encompass a variety of tissues like muscle, fat, skin, and blood vessels, which have diverse cellular compositions and arrangements 22 …”

3D Printing of Self‐Assembling Nanofibrous Multidomain Peptide Hydrogels

“…Although multiple 3D printing methods exist, extrusion-based printing has been most widely adopted due to its simplistic working principle and ease of use. [3,4] Inks used in extrusion 3D printing mainly consist of chemically modified versions of gelatin, [5][6][7][8][9][10][11][12] alginate, [13][14][15][16] hyaluronic acid, [17][18][19][20] collagen, [1,21,22] decellularized extracellular matrix, [23][24][25] or combinations of these. [26][27][28][29][30][31][32][33][34][35] The traditional approach for developing 3D printable inks invented a fabrication method that included extrusion printing followed by spraying a salt gelling agent at each layer.…”

“…Although multiple 3D printing methods exist, extrusion‐based printing has been most widely adopted due to its simplistic working principle and ease of use. [ 3,4 ] Inks used in extrusion 3D printing mainly consist of chemically modified versions of gelatin, [ 5–12 ] alginate, [ 13–16 ] hyaluronic acid, [ 17–20 ] collagen, [ 1,21,22 ] decellularized extracellular matrix, [ 23–25 ] or combinations of these. [ 26–35 ] The traditional approach for developing 3D printable inks has been to chemically modify naturally‐derived hydrogel materials to make them more printable, while attempting to maintain their favorable biological properties.…”