A 3D Bioprinted Spheroid-Laden dECM-Enriched Osteosarcoma Model for Enhanced Drug Testing and Therapeutic Discovery

Sep 22, 2026

Osteosarcoma (OS) is the most common bone cancer with high mortality, driven by tumor heterogeneity, metastatic potential, and chemoresistance, creating an urgent need for preclinical models that better reflect disease biology. This study introduces a 3D bioprinted OS model incorporating OS spheroids into an OS-tailored, decellularized ECM–enriched bioink. The construct supports rapid UV gelation and improved biocompatibility while showing altered prognostic marker expression and reduced doxorubicin sensitivity, suggesting reliable platform potential for alternative OS therapeutics.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages19

Reading Time48 min

AccessFree to download

Introduction

Osteosarcoma background and clinical challenges

Need for improved preclinical models

Advantages and limitations of 2D and animal models

Advanced Healthcare Materials [www.advhealthmat.de](www.advhealthmat.de) RESEARCH ARTICLE A 3D Bioprinted Spheroid-Laden dECM-Enriched Osteosarcoma Model for Enhanced Drug Testing and Therapeutic Discovery Margarida F. Domingues1, 2 Maria Catarina Carreira1, 2 Mafalda S. Santos1, 2 Daniela Pacheco3 Frederico Castelo Ferreira1, 2 Paola Sanjuan-Alberte1, 2 João Carlos Silva1, 2 1 Department of Bioengineering and Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal 2Associate Laboratory i4HB–-Institute for Health and Bioeconomy, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal 3 Bac3Gel, Lda, Taguspark, Innov. Building II, Porto Salvo, Portugal Correspondence: Paola Sanjuan-Alberte ([paola.alberte@tecnico.ulisboa.pt](paola.alberte@tecnico.ulisboa.pt)) João Carlos Silva (joao.f.da.silva@tecnico.ulisboa.pt) Received: 22 July 2025 Revised: 15 January 2026 Accepted: 21 January 2026 Keywords: 3D bioprinting | 3D model | bioink | decellularized extracellular matrix | doxorubicin | osteosarcoma | spheroids ABSTRACT Osteosarcoma (OS) is the most common bone cancer, characterized by high mortality rates and limited treatment options, due to its heterogeneity, metastatic potential, and chemoresistance. This highlights the urgent need for robust preclinical models that accurately represent the disease in order to facilitate the discovery of new therapeutics. Compared to traditional 2D cultures and animal models, 3D in vitro models offer a better representation of the tumor’s 3D structure and cell-extracellular matrix (ECM) interactions, which play a key role in drug response, while reducing the need for animal testing. In this work, we present a novel 3D bioprinted OS model by incorporating OS spheroids into an OS-tailored bioink, enriched with OS cell-derived decellularized ECM. The bioink exhibits high water content, minimal mass loss, fast UV-induced gelation, and enhanced printability and biocompatibility. Despite having a compressive modulus at the lower end of the range associated with OS, the bioprinted model shows an increased expression of OS prognostic markers, lower sensitivity to doxorubicin, and overexpression of P-glycoprotein. This is likely due to the model’s ability to mimic both the 3D structure and composition of the OS-ECM, emphasizing its enhanced reliability and potential for exploring novel alternative OS therapeutic approaches in future research. 1 Introduction Osteosarcoma (OS) is the most prevalent primary malignant bone cancer, mainly affecting children and adolescents [1] . Despite its rarity, with an annual incidence of 3.4 cases per million people and comprising 1% and 3%–5% of adult and pediatric cancers, respectively [2–4], OS remains highly lethal. Its treatment strategy has seen minimal advancements since the 1970s and primarily consists of adjuvant and/or neoadjuvant MAP-therapy [1, 5], which includes the chemotherapeutics methotrexate, adriamycin (doxorubicin), and platinol (cisplatin), combined with surgi- cal tumor resection [5] . Amputation may still be required for non-resectable tumors (10%–15% of cases) [3] . Despite ongoing efforts to discover more effective anticancer drugs and therapies, survival rates for OS have remained stagnant for decades: the 5-year event-free survival rate is 76% for primary OS and 24% for metastatic and recurrent disease [4] . Additionally, recurrence within three years of treatment occurs in approximately 20% and 80% of patients with localized and metastatic disease, respectively [6] . These poor outcomes can be attributed to several factors, namely the inherent heterogeneous nature of OS (both within and between patients), its aggressive metastatic spread This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work

FAQs

Why is there an urgent need for improved preclinical OS models?

OS has high mortality and limited treatment options due to heterogeneity, metastatic potential, and chemoresistance. The document highlights that traditional models often fail to translate into clinical success.

What is the core design of the proposed 3D bioprinted OS model?

The model incorporates OS spheroids into an OS-tailored bioink enriched with OS cell-derived decellularized extracellular matrix (ECM).

How does the bioprinted model respond to doxorubicin compared with expectations from conventional models?

The bioprinted model shows lower sensitivity to doxorubicin and features increased expression of OS prognostic markers, along with overexpression of P-glycoprotein.

Sep 22, 2026

Uploaded by Riley West