Therapeutic Ultrasound in Experimental Animal Models: Biophysical Foundations, Tissue-Specific Effects, and Translational Perspectives

Öz

Therapeutic ultrasound (TUS) is a non-invasive biophysical modality that has gained increasing attention in experimental animal research for its ability to modulate tissue repair, regeneration, and neuromodulation primarily through controlled mechanical stimulation accompanied by minimal sub-thermal heating. Evidence derived largely from rodent and other preclinical animal models demonstrates that low-intensity pulsed or focused ultrasound (LIPUS/LIFU) elicits biologically relevant responses across a wide range of tissues, including bone, tendon, skeletal muscle, peripheral nerves, skin, ocular tissues, and the central nervous system. These effects are associated with enhanced cellular proliferation, angiogenesis, extracellular matrix organization, neurotrophic signaling, and attenuation of inflammatory responses. In contrast, high-intensity focused ultrasound (HIFU) concentrates acoustic energy to induce rapid temperature elevations and coagulative necrosis, serving fundamentally different, predominantly ablative therapeutic purposes. The biological outcomes of TUS are highly dependent on acoustic parameters such as frequency, intensity, duty cycle, exposure duration, and coupling conditions, underscoring the critical importance of carefully controlled experimental protocols in animal studies. Although low-intensity ultrasound is generally considered safe, substantial heterogeneity in dosimetry, operator-dependent variability, and narrow safety margins in sensitive tissues, particularly the eye and central nervous system, remain important limitations for translational application. This narrative review synthesizes current experimental animal literature on the biophysical foundations and tissue-specific effects of TUS, clearly distinguishing biomodulatory low-intensity approaches from ablative HIFU applications, and highlights key methodological considerations that must be addressed to facilitate reliable translation into veterinary and biomedical practice.

Anahtar Kelimeler

• Therapeutic ultrasound
• animal models
• tissue regeneration
• neuromodulation
• wound healing
• bone healing

Therapeutic Ultrasound in Experimental Animal Models: Biophysical Foundations, Tissue-Specific Effects, and Translational Perspectives

Öz

Terapötik ultrason (TUS), kontrollü mekanik uyarılar ve minimal düzeyde sub-termal ısınma yoluyla doku onarımı, rejenerasyon ve nöromodülasyonu modüle edebilen non-invaziv bir biyofiziksel yöntem olarak deneysel hayvan araştırmalarında giderek artan ilgi görmektedir. Başta kemirgenler olmak üzere preklinik hayvan modellerinden elde edilen bulgular, düşük yoğunluklu darbeli veya odaklanmış ultrasonun (LIPUS/LIFU) kemik, tendon, iskelet kası, periferik sinir, deri, oküler dokular ve merkezi sinir sistemi gibi çok sayıda dokuda biyolojik olarak anlamlı yanıtlar oluşturduğunu göstermektedir. Bu yanıtlar; hücresel proliferasyonun, anjiyogenezin, ekstrasellüler matriks organizasyonunun ve nörotrofik sinyallemenin artması ile inflamatuvar yanıtların baskılanması gibi mekanizmalarla ilişkilendirilmektedir. Buna karşılık yüksek yoğunluklu odaklanmış ultrason (HIFU), akustik enerjiyi fokal bir noktada yoğunlaştırarak hızlı sıcaklık artışı ve koagülatif nekroz oluşturan, esas olarak ablasyon amaçlı kullanılan farklı bir terapötik yaklaşımı temsil etmektedir. TUS’un biyolojik etkileri; frekans, yoğunluk, görev döngüsü, uygulama süresi ve coupling koşulları gibi akustik parametrelere yüksek derecede bağımlıdır ve bu durum deneysel hayvan çalışmalarında titizlikle kontrol edilen protokollerin önemini ortaya koymaktadır. Düşük yoğunluklu ultrason genel olarak güvenli kabul edilse de, dozimetrideki heterojenlik, operatöre bağlı değişkenlik ve özellikle göz ile merkezi sinir sistemi gibi hassas dokulardaki dar güvenlik aralıkları translasyonel uygulamalar açısından önemli sınırlılıklar oluşturmaktadır. Bu derleme, terapötik ultrasonun biyofiziksel temellerini ve dokuya özgü etkilerini deneysel hayvan modelleri üzerinden sentezleyerek, düşük yoğunluklu biyomodülatör yaklaşımlar ile ablasyon amaçlı HIFU uygulamaları arasındaki farkları ortaya koymakta ve veteriner ile biyomedikal alanlarda güvenilir translasyon için dikkate alınması gereken metodolojik hususları vurgulamaktadır.

Anahtar Kelimeler

• Terapötik ultrason
• hayvan modelleri
• doku rejenerasyonu
• nöromodülasyon
• ; yara iyileşmesi
• kemik iyileşmesi

Kaynakça

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