Use of an Injectable PCL-HA Composite with Tissue Regenerative Matrix to Promote Adipose Tissue Ingrowth in Soft Tissue Defects
Georgia C Yalanis, M.Sc.1, Sashank Reddy, M.D.1, Russ Martin, Ph.D.2, Jisuk Choi, Ph.D.2, Gerald Brandacher, M.D.1, Justin M Sacks, M.D.1.
1Johns Hopkins University School of Medicine, Baltimore, MD, USA, 2Johns Hopkins University Whiting School of Engineering, Baltimore, MD, USA.
Purpose: Reconstructive procedures for soft tissue losses lead to functional and aesthetic disturbances, infection, or fibrosis. Existing injectable materials lack structural integrity to reconstruct large, 3-D volumes; fail to regenerate tissue; and offer transient resorption. We present a bioresorbable injectable synthetic that promotes tissue recruitment to promote soft tissue restoration.
Methods: Polyester nanofibers were cryo-milled to disperse fibers inside hyaluronic acid (HA) hydrogels. Solutions were incubated at 37 C for 20’, set for 10’ in syringes, and injected into the inguinal fat pad of Lewis rats using a modified serial puncture technique, with a 15" post-injection massage. Tissues were explanted en bloc at 7-, 30-, and 90- days, fixed, and stained with Masson’s Trichrome and perilipin.
Results: Rapid MSC migration is observed due to optimal porosity and ECM-like ultrastructure. Masson’s Trichrome staining demonstrates superior biocompatibility and integration without evidence of inflammation or fibrosis. Injectable composites have enhanced ability to promote MSC differentiation demonstrated by early incorporation at the TZI (transformation zone interface). Early histology is indicative of adipogenesis (Figure 1).
Conclusion: We have developed an injectable, synthetic composite with structural integrity to replace large defects while promoting tissue integration. Our material has long-term permanence, maintaining 3-D shape and structure, and promoting adipose tissue formation without evidence of foreign body response. Use of our injectable PCL-HA composite has significant implications for permanently reconstituting soft tissue defects.
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