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Open AccessArticle
Establishment of Vasculature in Hyper-Crosslinked Carbohydrate Polymer as Scaffolding for Tissue Engineering and Regeneration
by
Evan T. Lee
Evan T. Lee
Plamena M. Koleva
Plamena M. Koleva
Kee D. Kim
Kee D. Kim
Cynthia A. Batchelder
Cynthia A. Batchelder 
1
Department of Neurological Surgery, University of California Davis Medical Center, Sacramento, CA 95816, USA
2
Molecular Matrix, Inc., Rancho Cordova, CA 95670, USA
*
Author to whom correspondence should be addressed.
Appl. Sci. 2026, 16(2), 722; https://doi.org/10.3390/app16020722 (registering DOI)
Submission received: 22 November 2025
/
Revised: 19 December 2025
/
Accepted: 6 January 2026
/
Published: 9 January 2026
Featured Application
Effective tissue repair and regeneration hinge on the establishment of a functional vascular network capable of delivering oxygen, nutrients, immune cells, and signaling molecules essential for intrinsic healing processes. In the context of bone grafts, substitutes, and engineered constructs, vascularization is particularly critical to prevent hypoxia-induced cell death and graft failure, especially in large or critical-sized defects. This study evaluated the vascularization potential of a novel hyper-crosslinked carbohydrate polymer (HCCP) bone graft substitute relative to hydroxyapatite/beta-tricalcium phosphate (HA/β-TCP), a widely used clinical comparator. Results demonstrated that HCCP significantly enhanced neovascular infiltration and reduced immunogenic response when compared with HA/β-TCP. These findings support HCCP’s potential as a next-generation bone graft material, particularly for applications requiring rapid vascular integration and low inflammatory burden.
Abstract
Vascularization is one of the key components of tissue engineering and must accompany the ingrowth of new tissues to establish an environment conducive to repair and regeneration of damaged tissue. The overarching objective of this study was to investigate whether the hyper-crosslinked carbohydrate polymer (HCCP) could promote the establishment of new vasculature compared to hydroxyapatite/beta-tricalcium phosphate (HA/β-TCP), which is widely used in orthopedic procedures. Sprague Dawley rats (n = 12) were implanted subcutaneously with HCCP or HA/β-TCP and evaluated histologically for the ingrowth of new vasculature at 3, 14, and 28 days post-implantation. HCCP showed significantly greater levels of vascularization when compared to HA/β-TCP at all time points evaluated (p < 0.05). HA/β-TCP showed transient inflammation at 14 days post-implantation, whereas minimal immune activities were noted in HCCP. These findings suggest that HCCP promotes the establishment of new vasculature without a significant immune response.
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MDPI and ACS Style
Lee, E.T.; Koleva, P.M.; Kim, K.D.; Batchelder, C.A.
Establishment of Vasculature in Hyper-Crosslinked Carbohydrate Polymer as Scaffolding for Tissue Engineering and Regeneration. Appl. Sci. 2026, 16, 722.
https://doi.org/10.3390/app16020722
AMA Style
Lee ET, Koleva PM, Kim KD, Batchelder CA.
Establishment of Vasculature in Hyper-Crosslinked Carbohydrate Polymer as Scaffolding for Tissue Engineering and Regeneration. Applied Sciences. 2026; 16(2):722.
https://doi.org/10.3390/app16020722
Chicago/Turabian Style
Lee, Evan T., Plamena M. Koleva, Kee D. Kim, and Cynthia A. Batchelder.
2026. "Establishment of Vasculature in Hyper-Crosslinked Carbohydrate Polymer as Scaffolding for Tissue Engineering and Regeneration" Applied Sciences 16, no. 2: 722.
https://doi.org/10.3390/app16020722
APA Style
Lee, E. T., Koleva, P. M., Kim, K. D., & Batchelder, C. A.
(2026). Establishment of Vasculature in Hyper-Crosslinked Carbohydrate Polymer as Scaffolding for Tissue Engineering and Regeneration. Applied Sciences, 16(2), 722.
https://doi.org/10.3390/app16020722
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