Coupling intraoperative bioprinting and surgical micropuncture for synergistic scaffold vascularization

Affiliations

¹ Engineering Science and Mechanics, Pennsylvania State University, University Park, PA, USA; Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, USA.
² Penn State Hershey Medical Center, Department of Surgery, Hershey, PA, USA; Penn State, College of Medicine, Hershey, PA, USA.
³ Penn State, College of Medicine, Hershey, PA, USA.
⁴ Engineering Science and Mechanics, Pennsylvania State University, University Park, PA, USA; Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, USA; Department of Neurosurgery, Penn State University, College of Medicine, Hershey, PA, USA; Penn State University, Department of Biomedical Engineering, State College, PA, USA; Materials Research Institute, Penn State University, University Park, PA, 16802, USA; Penn State Cancer Institute, Penn State University, Hershey, PA, 17033, USA; Department of Medical Oncology, Cukurova University, Adana, 01130, Turkey. Electronic address: ito1@psu.edu.
⁵ Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, USA; Penn State Hershey Medical Center, Department of Surgery, Hershey, PA, USA; Penn State, College of Medicine, Hershey, PA, USA. Electronic address: dur2@psu.edu.

PMID: 40974746
DOI: 10.1016/j.biomaterials.2025.123711

Coupling intraoperative bioprinting and surgical micropuncture for synergistic scaffold vascularization

Miji Yeo et al. Biomaterials. 2025.

. 2025 Sep 13:326:123711.

doi: 10.1016/j.biomaterials.2025.123711. Online ahead of print.

Affiliations

¹ Engineering Science and Mechanics, Pennsylvania State University, University Park, PA, USA; Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, USA.
² Penn State Hershey Medical Center, Department of Surgery, Hershey, PA, USA; Penn State, College of Medicine, Hershey, PA, USA.
³ Penn State, College of Medicine, Hershey, PA, USA.
⁴ Engineering Science and Mechanics, Pennsylvania State University, University Park, PA, USA; Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, USA; Department of Neurosurgery, Penn State University, College of Medicine, Hershey, PA, USA; Penn State University, Department of Biomedical Engineering, State College, PA, USA; Materials Research Institute, Penn State University, University Park, PA, 16802, USA; Penn State Cancer Institute, Penn State University, Hershey, PA, 17033, USA; Department of Medical Oncology, Cukurova University, Adana, 01130, Turkey. Electronic address: ito1@psu.edu.
⁵ Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, USA; Penn State Hershey Medical Center, Department of Surgery, Hershey, PA, USA; Penn State, College of Medicine, Hershey, PA, USA. Electronic address: dur2@psu.edu.

PMID: 40974746
DOI: 10.1016/j.biomaterials.2025.123711

Abstract

Intraoperative bioprinting (IOB) is an advanced approach enabling the reconstruction of tissue defects by precisely bioprinting biologics under surgical settings. However, IOB has limited translational potential in its current form secondary to difficulty in establishing a rapidly functional, anastomosed vascular network. Micropuncture (MP) is an innovative microsurgical approach that overcomes this obstacle by creating targeted perforations in the host macrovasculature to stimulate angiogenesis, thereby facilitating microvascular ingrowth into adjacent bioprinted constructs. This study presents the first attempt of MP-induced vascularization of intraoperatively bioprinted constructs (10 mm × 15 mm × 3 mm). After precise optimization of bioink and cell compositions, IOB was performed in rat hindlimbs using rat aortic endothelial cell (RAOEC)-laden bioink to synergistically promote vascularization in conjugation with MP. The combination of MP and RAOECs demonstrated the highest values across all parameters such as a 1.8-fold vessel density increase, 2-fold increase in vessel length, a 2.5-fold increase in PECAM-1 expression, and a 4.2-fold increase in F4/80 expression on Day 40 compared to the bioink-only group. Additionally, perfusion was observed in bioprinted constructs, confirming functional microvascular anastomoses to the host. Taken together, the present study proposes an advanced pre-clinical strategy that integrates IOB for customized bioprinted platforms with MP to rapidly achieve effective in-situ vascularization.

Keywords: Endothelial cells; Intraoperative bioprinting; Micropuncture; Surgery; Vascularization.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dino Ravnic reports financial support was provided by National Institutes of Health. Ibrahim Ozbolat reports financial support was provided by National Institutes of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Coupling intraoperative bioprinting and surgical micropuncture for synergistic scaffold vascularization

Affiliations

Coupling intraoperative bioprinting and surgical micropuncture for synergistic scaffold vascularization

Authors

Affiliations

Abstract

Conflict of interest statement

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