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Chitosan coatings with distinct innate immune bioactivities differentially stimulate angiogenesis, osteogenesis and chondrogenesis in poly-caprolactone scaffolds with controlled interconnecting pore size.

ABSTRACT: This study tested whether osseous integration into poly (ε-caprolactone) (PCL) bioplastic scaffolds with fully-interconnecting 155 ± 8 μm pores is enhanced by an adhesive, non-inflammatory 99% degree of deacetylation (DDA) chitosan coating (99-PCL), or further incorporation of pro-inflammatory 83% DDA chitosan microparticles (83-99-PCL) to accelerate angiogenesis. New Zealand White rabbit osteochondral knee defects were press-fit with PCL, 99-PCL, 83-99-PCL, or allowed to bleed (drill-only). Between day 1 and 6 weeks of repair, drill-only defects repaired by endochondral ossification, with an 8-fold higher bone volume fraction (BVF) versus initial defects, compared to a 2-fold (99-PCL), 1.1-fold (PCL), or 0.4-fold (83-99-PCL) change in BVF. Hematoma innate immune cells swarmed to 83-99-PCL, elicited angiogenesis throughout the pores and induced slight bone resorption. PCL and 99-PCL pores were variably filled with cartilage or avascular mesenchyme near the bone plate, or angiogenic mesenchyme into which repairing trabecular bone infiltrated up to 1 mm deep. More repair cartilage covered the 99-PCL scaffold (65%) than PCL (18%) or 83-99-PCL (0%) (p < 0.005). We report the novel finding that non-inflammatory chitosan coatings promoted cartilage infiltration into and over a bioplastic scaffold, and were compatible with trabecular bone integration. This study also revealed that in vitro osteogenesis assays have limited ability to predict osseous integration into porous scaffolds, because (1) in vivo, woven bone integrates from the leading edge of regenerating trabecular bone and not from mesenchymal cells adhering to scaffold surfaces, and (2) bioactive coatings that attract inflammatory cells induce bone resorption.

SUBMITTER: Hoemann CD

PROVIDER: S-EPMC8636821 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Natural medicines have long been used to treat physiological ailments where both ginger (gingerol) and garlic (allicin) are key players in immune system promotion, reduction in blood pressure, and lowering inflammation response. With their efficacy in bone healing, these compounds have great value as medicinal additives in bone scaffolds for localized treatment to support tissue formation, along with providing their natural therapeutic benefits. Utilization of 3D-printed (3DP) bone tissue engineering scaffolds as drug delivery vehicles for ginger and garlic extracts enables patient specificity in bone defect applications with enhanced osseointegration. Our objective is to understand their combined efficacy on osteogenesis when released from 3DP calcium phosphate bone scaffolds designed with a bimodal pore distribution. With a porous core and dense exterior, the resulting scaffolds have good mechanical integrity with 10 ± 1 MPa compressive strengths. Results show that ginger + garlic extracts released from bone scaffolds enhance their osteogenic potential through on site drug delivery. Both compounds exhibit exponential drug release profiles which fit Weibull distribution equations. The release of ginger extract also increases osteoblast proliferation by 59%. Both compounds show decreased osteoclast resorption activity, with a greater than 20% reduction in pit area on sample surfaces. Ginger + garlic extract induces a twofold increase in early osteoid tissue formation in vivo at week 4, in addition to a 30% increase in total bone area and a 90% increase in osteocytes with respect to control 3DP tricalcium phosphate scaffolds. Late-stage bone healing at week 10 reveals healthy angiogenic tissue, a twofold higher bone mineralization, and significant enhancement of type I collagen formation in the presence of ginger and garlic extracts. Naturally sourced ginger and garlic extracts provide osteogenic promotion and improved bone tissue in-growth in a patient-specific 3DP scaffold biomedical device for low load-bearing bone tissue engineering and dental applications.

Dataset Information

Chitosan coatings with distinct innate immune bioactivities differentially stimulate angiogenesis, osteogenesis and chondrogenesis in poly-caprolactone scaffolds with controlled interconnecting pore size.

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