Daniel Max Weber

Foreign body response (FBR) is a pervasive problem for biomaterials used in tissue engineering. Zwitterionic hydrogels have emerged as an effective solution to this problem, due to their ultra-low fouling properties, which enable them to effectively inhibit FBR in vivo. However, no versatile zwitterionic bioink that allows for high resolution extrusion bioprinting of tissue implants has thus far been reported. In this work, we introduce a simple, novel method for producing zwitterionic microgel bioink, using alginate methacrylate (AlgMA) as crosslinker and mechanical fragmentation as a microgel fabrication method. Photocrosslinked hydrogels made of zwitterionic carboxybetaine acrylamide (CBAA) and sulfobetaine methacrylate (SBMA) are mechanically fragmented through meshes with aperture diameters of 50 and 90 µm to produce microgel bioink. The bioinks made with both microgel sizes showed excellent rheological properties and were used for high-resolution printing of objects with overhanging features without requiring a support structure or support bath. The AlgMA crosslinker has a dual role, allowing for both primary photocrosslinking of the bulk hydrogel as well as secondary ionic crosslinking of produced microgels, to quickly stabilize the printed construct in a calcium bath and to produce a microporous scaffold. Scaffolds showed ∼20% porosity, and they supported viability and chondrogenesis of encapsulated human primary chondrocytes. Finally, a meniscus model was bioprinted, to demonstrate the bioink’s versatility at printing large, cell-laden constructs which are stable for further in vitro culture to promote cartilaginous tissue production. This easy and scalable strategy of producing zwitterionic microgel bioink for high resolution extrusion bioprinting allows for direct cell encapsulation in a microporous scaffold and has potential for in vivo biocompatibility due to the zwitterionic nature of the bioink.

Tissue engineering approaches that recapitulate cartilage biomechanical properties are emerging as promising methods to restore the function of injured or degenerated tissue. However, despite significant progress in this research area, the generation of engineered cartilage constructs akin to native counterparts still represents an unmet challenge. In particular, the inability to accurately reproduce cartilage zonal architecture with different collagen fibril orientations is a significant limitation. The arrangement of the extracellular matrix (ECM) plays a fundamental role in determining the mechanical and biological functions of the tissue. In this study, it is shown that a novel light‐based approach, Filamented Light (FLight) biofabrication, can be used to generate highly porous, 3D cell‐instructive anisotropic constructs that lead to directional collagen deposition. Using a photoclick‐based photoresin optimized for cartilage tissue engineering, a significantly improved maturation of the cartilaginous tissues with zonal architecture and remarkable native‐like mechanical properties is demonstrated.

Zwitterionic hydrogels have high potential for cartilage tissue engineering due to their ultra‐hydrophilicity, nonimmunogenicity, and superior antifouling properties. However, their application in this field has been limited so far, due to the lack of injectable zwitterionic hydrogels that allow for encapsulation of cells in a biocompatible manner. Herein, a novel strategy is developed to engineer cartilage employing zwitterionic granular hydrogels that are injectable, self‐healing, in situ crosslinkable and allow for direct encapsulation of cells with biocompatibility. The granular hydrogel is produced by mechanical fragmentation of bulk photocrosslinked hydrogels made of zwitterionic carboxybetaine acrylamide (CBAA), or a mixture of CBAA and zwitterionic sulfobetaine methacrylate (SBMA). The produced microgels are enzymatically crosslinkable using horseradish peroxidase, to quickly stabilize the construct, resulting in a microporous hydrogel. Encapsulated human primary chondrocytes are highly viable and able to proliferate, migrate, and produce cartilaginous extracellular matrix (ECM) in the zwitterionic granular hydrogel. It is also shown that by increasing hydrogel porosity and incorporation of SBMA, cell proliferation and ECM secretion are further improved. This strategy is a simple and scalable method, which has high potential for expanding the versatility and application of zwitterionic hydrogels for diverse tissue engineering applications.

(1) Background: Carpal tunnel syndrome (CTS), a compressive mononeuropathy of the median nerve at the wrist, is rare in childhood and occurs most frequently due to secondary causes. (2) Methods: Medical history, electrodiagnostic findings, and imaging data of patients with CTS from two pediatric neuromuscular centers were analyzed retrospectively. The etiology of CTS was investigated and compared with the literature. (3) Results: We report on a cohort of 38 CTS patients (n = 22 females, n = 29 bilateral, mean age at diagnosis 9.8 years). Electrodiagnostic studies of all patients revealed slowing of the antidromic sensory or orthodromic mixed nerve conduction velocities across the carpal tunnel or lack of the sensory nerve action potential and/or prolonged distal motor latencies. Median nerve ultrasound was diagnostic for CTS and confirmed tumorous and vascular malformations. Etiology was secondary in most patients (n = 29; 76%), and mucopolysaccharidosis was the most frequent underlying condition (n = 14; 37%). Idiopathic CTS was rare in this pediatric cohort (n = 9; 24%). (4) Conclusion: Since CTS in childhood is predominantly caused by an underlying disorder, a thorough evaluation and search for a causative condition is recommended in this age group.