Anti‐VEGF antibody delivered locally reduces bony bar formation following physeal injury in rats

Erickson, Christopher B.; Newsom, Jake P.; Fletcher, Nathan A.; Yu, Yangyi; Rodríguez-Fontán, Francisco; Weatherford, Shane; Hadley-Miller, Nancy; Krebs, Melissa D.; Payne, Karin A.

doi:10.1002/jor.24907

Cited by 8 publications

(11 citation statements)

References 51 publications

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“…Sections in the middle of the injury site were stained using ABH (a composite stain of Alcian Blue, Hematoxylin, Orange G, Phloxine B, and Eosin Y), which has been used extensively in growth plate research and stains cartilage blue, bone orange to red, fibrous tissue pink, and the chitosan microgels dark red. 20,25–27 While ABH stain cannot specifically stain for the chitosan microgels, they seem to appear as a dark red fibrous tissue which is not observed in the untreated group that does not receive chitosan microgels. Based on this dark red staining, the degradation of the chitosan microgels at each time point could be evaluated.…”

Section: Methodsmentioning

confidence: 94%

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

et al. 2021

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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.

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Section: Methodsmentioning

confidence: 94%

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

et al. 2021

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“… 68 While in terms of tissue engineering, the local delivery of Anti-VEGF antibody from ALG/CH hydrogels prevented bony bar formation in physeal injuries. 97 …”

Section: Controlled Delivery Of Therapeutic Biomolecules From Polysac...mentioning

confidence: 99%

“…In another study, a dynamic covalent Schiff-base bond was used for the formation of glycol-CH and oxidized ALG for the release of the same monoclonal antibody for the treatment of age-related macular degeneration . While in terms of tissue engineering, the local delivery of Anti-VEGF antibody from ALG/CH hydrogels prevented bony bar formation in physeal injuries …”

Section: Controlled Delivery Of Therapeutic Biomolecules From Polysac...mentioning

confidence: 99%

“…68 While in terms of tissue engineering, the local delivery of Anti-VEGF antibody from ALG/CH hydrogels prevented bony bar formation in physeal injuries. 97 Several researchers found the implementation of CH hydrogels useful for the encapsulation of different GFs. In the tissue engineering field, bone morphogenetic protein 6 (BMP-6) and TGF-β3 with human ASCs were included into microspheres: a photopolymerizable N-methacrylate glycol CH in situ forming hydrogel was used to incorporate such cargo, enhancing the expression of chondrogenic markers.…”

Section: Formation Of Polysaccharide-basedmentioning

confidence: 99%

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Recent Progress on Polysaccharide-Based Hydrogels for Controlled Delivery of Therapeutic Biomolecules

Rial-Hermida

Rey‐Rico

Blanco-Fernandez

et al. 2021

ACS Biomater. Sci. Eng.

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A plethora of applications using polysaccharides have been developed in recent years due to their availability as well as their frequent nontoxicity and biodegradability. These polymers are usually obtained from renewable sources or are byproducts of industrial processes, thus, their use is collaborative in waste management and shows promise for an enhanced sustainable circular economy. Regarding the development of novel delivery systems for biotherapeutics, the potential of polysaccharides is attractive for the previously mentioned properties and also for the possibility of chemical modification of their structures, their ability to form matrixes of diverse architectures and mechanical properties, as well as for their ability to maintain bioactivity following incorporation of the biomolecules into the matrix. Biotherapeutics, such as proteins, growth factors, gene vectors, enzymes, hormones, DNA/RNA, and antibodies are currently in use as major therapeutics in a wide range of pathologies. In the present review, we summarize recent progress in the development of polysaccharide-based hydrogels of diverse nature, alone or in combination with other polymers or drug delivery systems, which have been implemented in the delivery of biotherapeutics in the pharmaceutical and biomedical fields.

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“…[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.…”

Section: Introductionmentioning

confidence: 99%

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

Stager

Thomas

Rotello-Kuri

et al. 2022

Macromolecular Bioscience

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The growth plate is a complex cartilage structure in long bones that mediates growth in children. When injured, the formation of a "bony bar" can occur which impedes normal growth and can cause angular deformities or growth arrest. Current treatments for growth plate injuries are limited and result in poor patient outcomes, necessitating research toward novel treatments that can prevent bony bar formation and stimulate cartilage regeneration. This study investigates alginate-chitosan polyelectrolyte complex (PEC) hydrogels as an injectable biomaterial system to prevent bony bar formation. Biomaterial properties including stiffness and degradation are quantified, and the effect that material properties have on mesenchymal stem cell (MSC) fate is quantified in vitro. Specifically, this study aims to elucidate the effectiveness of biomaterial-based control over the differentiation behavior of MSCs toward osteogenic or chondrogenic lineages using biochemical metabolite assays and quantitative real time PCR. Further, the PEC hydrogels are employed in a rat growth plate injury model to determine their effectiveness in preventing bony bar formation in vivo. Results indicate that hydrogel composition and material properties affect the differentiation tendency of MSCs in vitro, and the PEC hydrogels show promise as an injectable biomaterial for growth plate injuries.

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Anti‐VEGF antibody delivered locally reduces bony bar formation following physeal injury in rats

Cited by 8 publications

References 51 publications

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

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

Recent Progress on Polysaccharide-Based Hydrogels for Controlled Delivery of Therapeutic Biomolecules

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

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