Emulsion-free chitosan–genipin microgels for growth plate cartilage regeneration

Abstract

The growth plate is a cartilage tissue near the ends of children’s long bones and is responsible for bone growth. Injury to the growth plate can result in the formation of a ‘bony bar’ which can span the growth plate and result in bone growth abnormalities in children. Biomaterials such as chitosan microgels could be a potential treatment for growth plate injuries due to their chondrogenic properties, which can be enhanced through loading with biologics. They are commonly fabricated via an emulsion method, which involves solvent rinses that are cytotoxic. Here, we present a high throughput, non-cytotoxic, non-emulsion-based method to fabricate chitosan–genipin microgels. Chitosan was crosslinked with genipin to form a hydrogel network, and then pressed through a syringe filter using mesh with various pore sizes to produce a range of microgel particle sizes. The microgels were then loaded with chemokines and growth factors and their release was studied in vitro. To assess the applicability of the microgels for growth plate cartilage regeneration, they were injected into a rat growth plate injury. They led to increased cartilage repair tissue and were fully degraded by 28 days in vivo. This work demonstrates that chitosan microgels can be fabricated without solvent rinses and demonstrates their potential for the treatment of growth plate injuries.

Magnetically powered chitosan milliwheels for rapid translation, barrier function rescue, and delivery of therapeutic proteins to the inflamed gut epithelium

“…Swelling and encapsulation allows for increased loading efficiency without crosslinking the antibodies to the matrix. 30,47 m-Wheels fabricated with different crosslinking densities and the pH of their respective release mediums alter the aTNF release. While the stomach has a pH of 1.5 to 3.0, which often requires capsules and other delivery coatings to protect therapeutic agents from degradation, 50,51 the pH of the lower GIT fluctuates between 5.7 to 7.4.…”

“…1A). 30 In this, low molecular weight chitosan was first purified by dissolving in 1% acetic acid to a concentration of 1% (w/v), vacuum filtered through a 22 μm filter, and then lyophilized. The purified chitosan was then dissolved in deionized H 2 O (diH 2 O) at 4% (w/v) along with 4% (w/v) iron oxide powder.…”

Polyelectrolyte Complex Hydrogels with Controlled Mechanics Affect Mesenchymal Stem Cell Differentiation Relevant to Growth Plate Injuries

“…For example, previous work in our group has determined that soluble factors such as anti-VEGF, TGF-𝛽1, or SDF-1𝛼 show promise in regenerating cartilage in growth plate injuries when employed in sustained release biomaterial systems. [26][27][28][29] Therefore, future work on PECs as an injectable hydrogel for growth plate injuries could include sustained release of cell signaling factors that improve cartilage regeneration or prevent the formation of a bony bar.…”

“…[24][25][26] Our team has also employed our biomaterials in a rat physeal injury model where they show promise for cartilage regeneration in a material-dependent manner. [27][28][29] However, further research is required to develop biomaterial systems that more effectively prevent bony bar formation while also promoting the regeneration of healthy tissue. In recent years, significant effort has been dedicated to investigating biomaterialmediated mechanotransduction as a method to control stem cell differentiation.…”

Growing Pains: The Need for Engineered Platforms to Study Growth Plate Biology

“…Erickson et al utilized chitosan‐genipin microgels to increase growth plate cartilage regeneration in a 28 day rat growth plate model. [ 194 ] The properties of granular hydrogels can be tailored to one's specific needs by changing the polymer used to form the microgels, utilizing different microparticle fabrication methods, and culturing tissue‐specific cell types.…”